Breast Cancer

While more than half of women aged 75 years and older receive annual mammograms, they do not see a reduced risk of death from breast cancer, compared with women who have stopped regular screening, according to a study published in Annals of Internal Medicine.

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The lack of benefit is not because older women’s cancer risk is low; a third of breast cancer deaths occur in women diagnosed at or after age 70 years, according to study author Xabier García-Albéniz, MD, PhD, of Harvard University in Boston, and colleagues.

The lack of benefit is not because mammography is less effective in women older than 75 years; indeed, it becomes a better diagnostic tool as women age, said Otis Brawley, MD, of Johns Hopkins University, Baltimore, the author of an editorial related to the study. Rather, the lack of benefit is because breast cancer treatment in older women is less successful, he clarified.
 

Study details

Dr. García-Albéniz and colleagues looked at data from 1,058,013 women enrolled in Medicare across the United States during 2000-2008. All subjects were aged 70-84 years and had a life expectancy of at least 10 years, at least one recent mammogram, and no history of breast cancer.

There are little randomized trial data available on mammography and breast cancer deaths for women in their early 70s and none for women older than 75 years. To compensate for this, the researchers aimed to emulate a prospective trial by looking at deaths over an 8-year period for women aged 70 and older who either continued annual screening or stopped it. The investigators conducted separate analyses for women aged 70-74 years and those 75-84 years of age.

Diagnoses of breast cancer were, not surprisingly, higher in the continued-screening group, but this did not translate to serious reductions in death.

In the continued-screening group, the estimated 8-year risk for breast cancer was 5.5% in women aged 70-74 and 5.8% in women aged 75-84 years. Among women who stopped screening, the estimated 8-year risk for breast cancer was 3.9% in both age groups.

Among women aged 70-74 years, the estimated 8-year risk for breast cancer death was slightly reduced with continued screening: 2.7 deaths per 1,000 women, compared with 3.7 deaths per 1,000 women for those who stopped screening. The risk difference was –1.0 deaths per 1,000 women, and the hazard ratio was 0.78.

Among women aged 75-84 years, there was no difference in estimated 8-year risk for breast cancer death. Women treated under a continued screening protocol had 3.8 deaths per 1,000, while the stop-screening group had 3.7 deaths per 1,000. The risk difference was 0.07 deaths per 1,000 women, and the hazard ratio was 1.00.

Interpreting the results

In the editorial accompanying this study, Dr. Brawley praised its design as “especially useful in breast cancer screening,” as “prospective randomized studies of mammography are not feasible and are perhaps no longer ethical in older women … because mammography is so widely accepted.”

In an interview, Dr. Brawley stressed that the findings do not argue for denying women aged 75 years and older mammography screening. Decisions about screening require a value judgment tailored to each individual patient’s perceived risks and benefits, he said.

In the absence of randomized trial evidence, “the jury will always be out” on the benefits of regular mammography for women 75 and older, Dr. Brawley said. “A clinical trial or a modeling study always tells you about an average person who doesn’t exist,” he added. “I predict that, in the future, we will have more parameters to tell us, ‘this is a person who’s 80 years old who is likely to benefit from screening; this is a person who is 75 years old who is unlikely to benefit.’ ”

And focusing too much on screening, he said, can divert attention from a key driver of breast cancer mortality in older women: inadequate treatment.

In the United States, Dr. Brawley said, “There’s a lot of emphasis on screening but fewer people writing about the fact that nearly 40% of American women get less than optimal treatment once they’re diagnosed.”

Dr. Brawley cited a 2013 modeling study showing that improvements in delivering current treatments would save more women even if screening rates remained unaltered (Cancer. 2013 Jul 15;119[14]:2541-8).

Among women in their 70s and 80s, Dr. Brawley said, some of the barriers to effective breast cancer care aren’t related to treatment efficacy but to travel and other logistical issues that can become more pronounced with age. “Unfortunately, there’s very little research on why, for women in their 70s and 80s, the treatments don’t work as well as they work in women 20 years younger,” he said.

Dr. García-Albéniz and colleagues’ study was funded by the National Institutes of Health. One coauthor reported financial ties to industry. Dr. Brawley discloses no conflicts of interest related to his editorial.

SOURCE: García-Albéniz X et al. Ann Intern Med 2020. doi: 10.7326/M18-1199.

While more than half of women aged 75 years and older receive annual mammograms, they do not see a reduced risk of death from breast cancer, compared with women who have stopped regular screening, according to a study published in Annals of Internal Medicine.

copyright/Thinkstock

The lack of benefit is not because older women’s cancer risk is low; a third of breast cancer deaths occur in women diagnosed at or after age 70 years, according to study author Xabier García-Albéniz, MD, PhD, of Harvard University in Boston, and colleagues.

The lack of benefit is not because mammography is less effective in women older than 75 years; indeed, it becomes a better diagnostic tool as women age, said Otis Brawley, MD, of Johns Hopkins University, Baltimore, the author of an editorial related to the study. Rather, the lack of benefit is because breast cancer treatment in older women is less successful, he clarified.
 

Study details

Dr. García-Albéniz and colleagues looked at data from 1,058,013 women enrolled in Medicare across the United States during 2000-2008. All subjects were aged 70-84 years and had a life expectancy of at least 10 years, at least one recent mammogram, and no history of breast cancer.

There are little randomized trial data available on mammography and breast cancer deaths for women in their early 70s and none for women older than 75 years. To compensate for this, the researchers aimed to emulate a prospective trial by looking at deaths over an 8-year period for women aged 70 and older who either continued annual screening or stopped it. The investigators conducted separate analyses for women aged 70-74 years and those 75-84 years of age.

Diagnoses of breast cancer were, not surprisingly, higher in the continued-screening group, but this did not translate to serious reductions in death.

In the continued-screening group, the estimated 8-year risk for breast cancer was 5.5% in women aged 70-74 and 5.8% in women aged 75-84 years. Among women who stopped screening, the estimated 8-year risk for breast cancer was 3.9% in both age groups.

Among women aged 70-74 years, the estimated 8-year risk for breast cancer death was slightly reduced with continued screening: 2.7 deaths per 1,000 women, compared with 3.7 deaths per 1,000 women for those who stopped screening. The risk difference was –1.0 deaths per 1,000 women, and the hazard ratio was 0.78.

Among women aged 75-84 years, there was no difference in estimated 8-year risk for breast cancer death. Women treated under a continued screening protocol had 3.8 deaths per 1,000, while the stop-screening group had 3.7 deaths per 1,000. The risk difference was 0.07 deaths per 1,000 women, and the hazard ratio was 1.00.

Interpreting the results

In the editorial accompanying this study, Dr. Brawley praised its design as “especially useful in breast cancer screening,” as “prospective randomized studies of mammography are not feasible and are perhaps no longer ethical in older women … because mammography is so widely accepted.”

In an interview, Dr. Brawley stressed that the findings do not argue for denying women aged 75 years and older mammography screening. Decisions about screening require a value judgment tailored to each individual patient’s perceived risks and benefits, he said.

In the absence of randomized trial evidence, “the jury will always be out” on the benefits of regular mammography for women 75 and older, Dr. Brawley said. “A clinical trial or a modeling study always tells you about an average person who doesn’t exist,” he added. “I predict that, in the future, we will have more parameters to tell us, ‘this is a person who’s 80 years old who is likely to benefit from screening; this is a person who is 75 years old who is unlikely to benefit.’ ”

And focusing too much on screening, he said, can divert attention from a key driver of breast cancer mortality in older women: inadequate treatment.

In the United States, Dr. Brawley said, “There’s a lot of emphasis on screening but fewer people writing about the fact that nearly 40% of American women get less than optimal treatment once they’re diagnosed.”

Dr. Brawley cited a 2013 modeling study showing that improvements in delivering current treatments would save more women even if screening rates remained unaltered (Cancer. 2013 Jul 15;119[14]:2541-8).

Among women in their 70s and 80s, Dr. Brawley said, some of the barriers to effective breast cancer care aren’t related to treatment efficacy but to travel and other logistical issues that can become more pronounced with age. “Unfortunately, there’s very little research on why, for women in their 70s and 80s, the treatments don’t work as well as they work in women 20 years younger,” he said.

Dr. García-Albéniz and colleagues’ study was funded by the National Institutes of Health. One coauthor reported financial ties to industry. Dr. Brawley discloses no conflicts of interest related to his editorial.

SOURCE: García-Albéniz X et al. Ann Intern Med 2020. doi: 10.7326/M18-1199.

While more than half of women aged 75 years and older receive annual mammograms, they do not see a reduced risk of death from breast cancer, compared with women who have stopped regular screening, according to a study published in Annals of Internal Medicine.

copyright/Thinkstock

The lack of benefit is not because older women’s cancer risk is low; a third of breast cancer deaths occur in women diagnosed at or after age 70 years, according to study author Xabier García-Albéniz, MD, PhD, of Harvard University in Boston, and colleagues.

The lack of benefit is not because mammography is less effective in women older than 75 years; indeed, it becomes a better diagnostic tool as women age, said Otis Brawley, MD, of Johns Hopkins University, Baltimore, the author of an editorial related to the study. Rather, the lack of benefit is because breast cancer treatment in older women is less successful, he clarified.
 

Study details

Dr. García-Albéniz and colleagues looked at data from 1,058,013 women enrolled in Medicare across the United States during 2000-2008. All subjects were aged 70-84 years and had a life expectancy of at least 10 years, at least one recent mammogram, and no history of breast cancer.

There are little randomized trial data available on mammography and breast cancer deaths for women in their early 70s and none for women older than 75 years. To compensate for this, the researchers aimed to emulate a prospective trial by looking at deaths over an 8-year period for women aged 70 and older who either continued annual screening or stopped it. The investigators conducted separate analyses for women aged 70-74 years and those 75-84 years of age.

Diagnoses of breast cancer were, not surprisingly, higher in the continued-screening group, but this did not translate to serious reductions in death.

In the continued-screening group, the estimated 8-year risk for breast cancer was 5.5% in women aged 70-74 and 5.8% in women aged 75-84 years. Among women who stopped screening, the estimated 8-year risk for breast cancer was 3.9% in both age groups.

Among women aged 70-74 years, the estimated 8-year risk for breast cancer death was slightly reduced with continued screening: 2.7 deaths per 1,000 women, compared with 3.7 deaths per 1,000 women for those who stopped screening. The risk difference was –1.0 deaths per 1,000 women, and the hazard ratio was 0.78.

Among women aged 75-84 years, there was no difference in estimated 8-year risk for breast cancer death. Women treated under a continued screening protocol had 3.8 deaths per 1,000, while the stop-screening group had 3.7 deaths per 1,000. The risk difference was 0.07 deaths per 1,000 women, and the hazard ratio was 1.00.

Interpreting the results

In the editorial accompanying this study, Dr. Brawley praised its design as “especially useful in breast cancer screening,” as “prospective randomized studies of mammography are not feasible and are perhaps no longer ethical in older women … because mammography is so widely accepted.”

In an interview, Dr. Brawley stressed that the findings do not argue for denying women aged 75 years and older mammography screening. Decisions about screening require a value judgment tailored to each individual patient’s perceived risks and benefits, he said.

In the absence of randomized trial evidence, “the jury will always be out” on the benefits of regular mammography for women 75 and older, Dr. Brawley said. “A clinical trial or a modeling study always tells you about an average person who doesn’t exist,” he added. “I predict that, in the future, we will have more parameters to tell us, ‘this is a person who’s 80 years old who is likely to benefit from screening; this is a person who is 75 years old who is unlikely to benefit.’ ”

And focusing too much on screening, he said, can divert attention from a key driver of breast cancer mortality in older women: inadequate treatment.

In the United States, Dr. Brawley said, “There’s a lot of emphasis on screening but fewer people writing about the fact that nearly 40% of American women get less than optimal treatment once they’re diagnosed.”

Dr. Brawley cited a 2013 modeling study showing that improvements in delivering current treatments would save more women even if screening rates remained unaltered (Cancer. 2013 Jul 15;119[14]:2541-8).

Among women in their 70s and 80s, Dr. Brawley said, some of the barriers to effective breast cancer care aren’t related to treatment efficacy but to travel and other logistical issues that can become more pronounced with age. “Unfortunately, there’s very little research on why, for women in their 70s and 80s, the treatments don’t work as well as they work in women 20 years younger,” he said.

Dr. García-Albéniz and colleagues’ study was funded by the National Institutes of Health. One coauthor reported financial ties to industry. Dr. Brawley discloses no conflicts of interest related to his editorial.

SOURCE: García-Albéniz X et al. Ann Intern Med 2020. doi: 10.7326/M18-1199.

Hot on the heels of a review from top nutrition scientists that cautioned against drinking cow’s milk comes another study with another caution: Drinking milk increases the risk of developing breast cancer, say the researchers. But this finding comes from an observational study, and there may be confounders that are not accounted for, says an expert not involved with the study.  

The latest research was based on data from the long-running larger study called Adventist Health Study-2 (AHS-2), which is looking at diet and health among Seventh Day Adventists in North America. Past results from this study have suggested that Seventh Day Adventists have longer life spans and lower rates of some cancers, perhaps because of healthier lifestyles.

The latest analysis suggests that milk raises breast cancer risk, and the more you drink the higher your risk may be.

“Consuming as little as 1/4 to 1/3 cup of dairy milk per day was associated with an increased risk of breast cancer of 30%,” first author Gary E. Fraser, MBChB, PhD, said in a press statement. Fraser is affiliated with the School of Public Health at Loma Linda University, California.

“By drinking up to 1 cup per day, the associated risk went up to 50%, and for those drinking 2 to 3 cups per day, the risk increased further to 70% to 80%,” he added.

The findings were published February 25 in the International Journal of Epidemiology.

“The AHS study is provocative, but it’s not enough to warrant a change in guidelines. The caution being espoused by the authors is not warranted given the observational nature of this study,” commented Don Dizon, MD, director of Women’s Cancers, Lifespan Cancer Institute at Brown University in Providence, Rhode Island. He was not involved with the study and was approached by Medscape Medical News for comment.

Because of its observational design, the study cannot prove that cow’s milk causes breast cancer, Dizon emphasized.

“I’d want to see if the findings are replicated [by others]. Outside of a randomized trial of [cow’s] milk vs no milk or even soy, and incident breast cancers, there will never be undisputable data,” he said.

“Probably the biggest point [about this study] is not to overinflate the data,” Dizon added.

He noted that the results were significant only for postmenopausal women, and not for premenopausal women. Moreover, analyses showed significant associations only for hormone receptor–positive cancers.

“We know that breast cancer increases in incidence with age, so this tracks with that particular trend. It suggests there may be confounders not accounted for in this study,” he said.

Research so far has been inconclusive on a possible link between dairy and increased risk for breast cancer. Dairy has even been tied to decreased risk for breast cancer, according to the World Cancer Research Fund.
 

Study Details

The current study included 52,795 Seventh Day Adventist women from North America who did not have cancer at the start of the study. Women had a mean age of 57.1 years, and 29.7% were black. At baseline, women reported their dietary patterns for the past year using food frequency questionnaires. For 1011 women, researchers double-checked food intake with 24-hour diet questionnaires, and verified soy intake by analyzing urine levels of soy isoflavones.

Data on invasive breast cancer diagnoses came from national registries in the US and Canada. Over the course of 7.9 years, 1057 women developed invasive breast cancer. Results were adjusted for a range of factors related to breast cancer risk, including diet, lifestyle, and family history of breast cancer.

Overall, women who consumed the most calories from dairy per day had 22% increased risk for breast cancer, compared with women with the fewest calories from dairy (hazard ratio, 1.22; 95% confidence interval, 1.05-1.40; P = .008). Women who drank the most cow›s milk per day had 50% increased risk for breast cancer compared with women who drank the least (HR, 1.50; 95% CI, 1.22 - 1.84; P less than .001). 

Drinking full or reduced fat cow’s milk did not change the findings (P for trend = .002 and P for trend less than .0001, respectively).

No significant association was found between breast cancer risk and cheese or yogurt consumption (P = .35 and P = .80, respectively).

Need for Change?

US dietary guidelines are under review. A new version, which will cover pregnant women and children under age 2 for the first time, is expected later this year.

Current guidelines recommend that adults and children aged 9 and over drink three 8 oz glasses of milk per day, or equivalent portions of yogurt, cheese, and other dairy products.

“Evidence from this study suggests that people should view that recommendation with caution,” Fraser said.
 

Milk Is Complex Topic

A top nutrition scientist agrees. Walter Willett, MD, DrPH, professor of epidemiology and nutrition at Harvard T.H. Chan School of Public Health in Boston, Massachusetts, told Medscape Medical News: “There is little scientific justification for the recommendation of 3 cups of milk per day. This new study adds a further reason for caution.” 

“This was a high-quality study conducted by experienced investigators,” Willett said. Strengths of the study include the high soy intake and low consumption of foods from animal sources, factors that are hard to study in other populations.

Willett was a coauthor, along with David Ludwig, MD, PhD, also from Harvard, of the recent review published in the New England Journal of Medicine that questioned the science behind milk-drinking recommendations. An article about this review on Medscape Medical News has attracted a huge number of comments from our readers.  

Milk is a complex topic, Willett explained. As a good source of essential nutrients, especially calcium and vitamin D, cow’s milk has been touted to have several health benefits, especially decreased fracture risk. But Willett said calcium recommendations have probably been overstated, and current evidence does not support high milk intake for fracture prevention.

Other benefits include improved nutrition in low-income settings, taller stature, and decreased colorectal cancer risk. But cow’s milk has also been linked to increased risk for some cancers, including prostate and endometrial cancer. Many of the benefits derived from nutrients found in milk may be obtained from other sources without these risks, according to Willett.

“Given the risks and benefits, we suggest a possible range from zero to two servings per day of dairy foods, including milk, cheese, and yogurt. If intake is zero or one serving, taking a calcium/vitamin D supplement would be good to consider,” he said.

However, Fraser and Willett also suggested another option: replacing cow’s milk with soy milk. Analyses from the current study showed no significant association between consumption of soy and breast cancer, independent of dairy (P for trend = .22).

In addition, substituting average amounts of soy milk for cow’s milk was linked to a 32% drop in risk for breast cancer among postmenopausal women (HR, 0.68; 95% CI, 0.55-0.85, P = .002). However, these results were not significant among premenopausal women (HR, 0.70; 95% CI, 0.36-1.38; P = .31).

“The suggestion that replacing some or all of [cow’s] milk with soy milk may reduce risk of breast cancer is consistent with other studies supporting a benefit of soy milk for risk of breast cancer,” Willett said.

“If someone does choose soy milk, picking one with minimal amounts of added sugar is desirable,” he added.

Drinking Milk, or Some Related Factor?

Fraser, the lead author of the current study, said in a statement that the results provide “fairly strong evidence that either dairy milk or some other factor closely related to drinking dairy milk is a cause of breast cancer in women.”

That ‘other’ factor is probably complicated, but may be related to what humans have done to cows. To increase milk production, humans have bred cows to have higher levels of insulin-like growth factor, which in turn has been linked to some cancers, including breast cancer.

Sex hormones in cow’s milk may also be involved. About 75% of a dairy herd is pregnant and the cows are by definition lactating. So the milk they produce may have higher levels of progestins and estrogens, which may play a role in hormone-responsive breast cancer. 

Other factors that researchers did not measure in this study, such as poverty and the income of participants, may be at play.

But to know what’s really going on, all agree that more research is needed.

“The overall evidence so far has not shown a clear increase or decrease in risk of breast cancer with higher [cow’s] milk intake. Thus, this topic needs further examination,” Willett said.

The study was funded by the National Cancer Institute at the National Institutes of Health, and the World Cancer Research Fund in the UK. Three of the authors report following largely vegetarian diets. All authors report regular and free use of dairy products without religious or other restrictions. No authors report associations with the soy product or dairy industries. Willett reports being a consultant during the design and early years of the Adventist study, but has not been involved with it for at least 8 years. Dizon has disclosed no relevant financial relationships.
 

This article first appeared on Medscape.com.

Hot on the heels of a review from top nutrition scientists that cautioned against drinking cow’s milk comes another study with another caution: Drinking milk increases the risk of developing breast cancer, say the researchers. But this finding comes from an observational study, and there may be confounders that are not accounted for, says an expert not involved with the study.  

The latest research was based on data from the long-running larger study called Adventist Health Study-2 (AHS-2), which is looking at diet and health among Seventh Day Adventists in North America. Past results from this study have suggested that Seventh Day Adventists have longer life spans and lower rates of some cancers, perhaps because of healthier lifestyles.

The latest analysis suggests that milk raises breast cancer risk, and the more you drink the higher your risk may be.

“Consuming as little as 1/4 to 1/3 cup of dairy milk per day was associated with an increased risk of breast cancer of 30%,” first author Gary E. Fraser, MBChB, PhD, said in a press statement. Fraser is affiliated with the School of Public Health at Loma Linda University, California.

“By drinking up to 1 cup per day, the associated risk went up to 50%, and for those drinking 2 to 3 cups per day, the risk increased further to 70% to 80%,” he added.

The findings were published February 25 in the International Journal of Epidemiology.

“The AHS study is provocative, but it’s not enough to warrant a change in guidelines. The caution being espoused by the authors is not warranted given the observational nature of this study,” commented Don Dizon, MD, director of Women’s Cancers, Lifespan Cancer Institute at Brown University in Providence, Rhode Island. He was not involved with the study and was approached by Medscape Medical News for comment.

Because of its observational design, the study cannot prove that cow’s milk causes breast cancer, Dizon emphasized.

“I’d want to see if the findings are replicated [by others]. Outside of a randomized trial of [cow’s] milk vs no milk or even soy, and incident breast cancers, there will never be undisputable data,” he said.

“Probably the biggest point [about this study] is not to overinflate the data,” Dizon added.

He noted that the results were significant only for postmenopausal women, and not for premenopausal women. Moreover, analyses showed significant associations only for hormone receptor–positive cancers.

“We know that breast cancer increases in incidence with age, so this tracks with that particular trend. It suggests there may be confounders not accounted for in this study,” he said.

Research so far has been inconclusive on a possible link between dairy and increased risk for breast cancer. Dairy has even been tied to decreased risk for breast cancer, according to the World Cancer Research Fund.
 

Study Details

The current study included 52,795 Seventh Day Adventist women from North America who did not have cancer at the start of the study. Women had a mean age of 57.1 years, and 29.7% were black. At baseline, women reported their dietary patterns for the past year using food frequency questionnaires. For 1011 women, researchers double-checked food intake with 24-hour diet questionnaires, and verified soy intake by analyzing urine levels of soy isoflavones.

Data on invasive breast cancer diagnoses came from national registries in the US and Canada. Over the course of 7.9 years, 1057 women developed invasive breast cancer. Results were adjusted for a range of factors related to breast cancer risk, including diet, lifestyle, and family history of breast cancer.

Overall, women who consumed the most calories from dairy per day had 22% increased risk for breast cancer, compared with women with the fewest calories from dairy (hazard ratio, 1.22; 95% confidence interval, 1.05-1.40; P = .008). Women who drank the most cow›s milk per day had 50% increased risk for breast cancer compared with women who drank the least (HR, 1.50; 95% CI, 1.22 - 1.84; P less than .001). 

Drinking full or reduced fat cow’s milk did not change the findings (P for trend = .002 and P for trend less than .0001, respectively).

No significant association was found between breast cancer risk and cheese or yogurt consumption (P = .35 and P = .80, respectively).

Need for Change?

US dietary guidelines are under review. A new version, which will cover pregnant women and children under age 2 for the first time, is expected later this year.

Current guidelines recommend that adults and children aged 9 and over drink three 8 oz glasses of milk per day, or equivalent portions of yogurt, cheese, and other dairy products.

“Evidence from this study suggests that people should view that recommendation with caution,” Fraser said.
 

Milk Is Complex Topic

A top nutrition scientist agrees. Walter Willett, MD, DrPH, professor of epidemiology and nutrition at Harvard T.H. Chan School of Public Health in Boston, Massachusetts, told Medscape Medical News: “There is little scientific justification for the recommendation of 3 cups of milk per day. This new study adds a further reason for caution.” 

“This was a high-quality study conducted by experienced investigators,” Willett said. Strengths of the study include the high soy intake and low consumption of foods from animal sources, factors that are hard to study in other populations.

Willett was a coauthor, along with David Ludwig, MD, PhD, also from Harvard, of the recent review published in the New England Journal of Medicine that questioned the science behind milk-drinking recommendations. An article about this review on Medscape Medical News has attracted a huge number of comments from our readers.  

Milk is a complex topic, Willett explained. As a good source of essential nutrients, especially calcium and vitamin D, cow’s milk has been touted to have several health benefits, especially decreased fracture risk. But Willett said calcium recommendations have probably been overstated, and current evidence does not support high milk intake for fracture prevention.

Other benefits include improved nutrition in low-income settings, taller stature, and decreased colorectal cancer risk. But cow’s milk has also been linked to increased risk for some cancers, including prostate and endometrial cancer. Many of the benefits derived from nutrients found in milk may be obtained from other sources without these risks, according to Willett.

“Given the risks and benefits, we suggest a possible range from zero to two servings per day of dairy foods, including milk, cheese, and yogurt. If intake is zero or one serving, taking a calcium/vitamin D supplement would be good to consider,” he said.

However, Fraser and Willett also suggested another option: replacing cow’s milk with soy milk. Analyses from the current study showed no significant association between consumption of soy and breast cancer, independent of dairy (P for trend = .22).

In addition, substituting average amounts of soy milk for cow’s milk was linked to a 32% drop in risk for breast cancer among postmenopausal women (HR, 0.68; 95% CI, 0.55-0.85, P = .002). However, these results were not significant among premenopausal women (HR, 0.70; 95% CI, 0.36-1.38; P = .31).

“The suggestion that replacing some or all of [cow’s] milk with soy milk may reduce risk of breast cancer is consistent with other studies supporting a benefit of soy milk for risk of breast cancer,” Willett said.

“If someone does choose soy milk, picking one with minimal amounts of added sugar is desirable,” he added.

Drinking Milk, or Some Related Factor?

Fraser, the lead author of the current study, said in a statement that the results provide “fairly strong evidence that either dairy milk or some other factor closely related to drinking dairy milk is a cause of breast cancer in women.”

That ‘other’ factor is probably complicated, but may be related to what humans have done to cows. To increase milk production, humans have bred cows to have higher levels of insulin-like growth factor, which in turn has been linked to some cancers, including breast cancer.

Sex hormones in cow’s milk may also be involved. About 75% of a dairy herd is pregnant and the cows are by definition lactating. So the milk they produce may have higher levels of progestins and estrogens, which may play a role in hormone-responsive breast cancer. 

Other factors that researchers did not measure in this study, such as poverty and the income of participants, may be at play.

But to know what’s really going on, all agree that more research is needed.

“The overall evidence so far has not shown a clear increase or decrease in risk of breast cancer with higher [cow’s] milk intake. Thus, this topic needs further examination,” Willett said.

The study was funded by the National Cancer Institute at the National Institutes of Health, and the World Cancer Research Fund in the UK. Three of the authors report following largely vegetarian diets. All authors report regular and free use of dairy products without religious or other restrictions. No authors report associations with the soy product or dairy industries. Willett reports being a consultant during the design and early years of the Adventist study, but has not been involved with it for at least 8 years. Dizon has disclosed no relevant financial relationships.
 

This article first appeared on Medscape.com.

Hot on the heels of a review from top nutrition scientists that cautioned against drinking cow’s milk comes another study with another caution: Drinking milk increases the risk of developing breast cancer, say the researchers. But this finding comes from an observational study, and there may be confounders that are not accounted for, says an expert not involved with the study.  

The latest research was based on data from the long-running larger study called Adventist Health Study-2 (AHS-2), which is looking at diet and health among Seventh Day Adventists in North America. Past results from this study have suggested that Seventh Day Adventists have longer life spans and lower rates of some cancers, perhaps because of healthier lifestyles.

The latest analysis suggests that milk raises breast cancer risk, and the more you drink the higher your risk may be.

“Consuming as little as 1/4 to 1/3 cup of dairy milk per day was associated with an increased risk of breast cancer of 30%,” first author Gary E. Fraser, MBChB, PhD, said in a press statement. Fraser is affiliated with the School of Public Health at Loma Linda University, California.

“By drinking up to 1 cup per day, the associated risk went up to 50%, and for those drinking 2 to 3 cups per day, the risk increased further to 70% to 80%,” he added.

The findings were published February 25 in the International Journal of Epidemiology.

“The AHS study is provocative, but it’s not enough to warrant a change in guidelines. The caution being espoused by the authors is not warranted given the observational nature of this study,” commented Don Dizon, MD, director of Women’s Cancers, Lifespan Cancer Institute at Brown University in Providence, Rhode Island. He was not involved with the study and was approached by Medscape Medical News for comment.

Because of its observational design, the study cannot prove that cow’s milk causes breast cancer, Dizon emphasized.

“I’d want to see if the findings are replicated [by others]. Outside of a randomized trial of [cow’s] milk vs no milk or even soy, and incident breast cancers, there will never be undisputable data,” he said.

“Probably the biggest point [about this study] is not to overinflate the data,” Dizon added.

He noted that the results were significant only for postmenopausal women, and not for premenopausal women. Moreover, analyses showed significant associations only for hormone receptor–positive cancers.

“We know that breast cancer increases in incidence with age, so this tracks with that particular trend. It suggests there may be confounders not accounted for in this study,” he said.

Research so far has been inconclusive on a possible link between dairy and increased risk for breast cancer. Dairy has even been tied to decreased risk for breast cancer, according to the World Cancer Research Fund.
 

Study Details

The current study included 52,795 Seventh Day Adventist women from North America who did not have cancer at the start of the study. Women had a mean age of 57.1 years, and 29.7% were black. At baseline, women reported their dietary patterns for the past year using food frequency questionnaires. For 1011 women, researchers double-checked food intake with 24-hour diet questionnaires, and verified soy intake by analyzing urine levels of soy isoflavones.

Data on invasive breast cancer diagnoses came from national registries in the US and Canada. Over the course of 7.9 years, 1057 women developed invasive breast cancer. Results were adjusted for a range of factors related to breast cancer risk, including diet, lifestyle, and family history of breast cancer.

Overall, women who consumed the most calories from dairy per day had 22% increased risk for breast cancer, compared with women with the fewest calories from dairy (hazard ratio, 1.22; 95% confidence interval, 1.05-1.40; P = .008). Women who drank the most cow›s milk per day had 50% increased risk for breast cancer compared with women who drank the least (HR, 1.50; 95% CI, 1.22 - 1.84; P less than .001). 

Drinking full or reduced fat cow’s milk did not change the findings (P for trend = .002 and P for trend less than .0001, respectively).

No significant association was found between breast cancer risk and cheese or yogurt consumption (P = .35 and P = .80, respectively).

Need for Change?

US dietary guidelines are under review. A new version, which will cover pregnant women and children under age 2 for the first time, is expected later this year.

Current guidelines recommend that adults and children aged 9 and over drink three 8 oz glasses of milk per day, or equivalent portions of yogurt, cheese, and other dairy products.

“Evidence from this study suggests that people should view that recommendation with caution,” Fraser said.
 

Milk Is Complex Topic

A top nutrition scientist agrees. Walter Willett, MD, DrPH, professor of epidemiology and nutrition at Harvard T.H. Chan School of Public Health in Boston, Massachusetts, told Medscape Medical News: “There is little scientific justification for the recommendation of 3 cups of milk per day. This new study adds a further reason for caution.” 

“This was a high-quality study conducted by experienced investigators,” Willett said. Strengths of the study include the high soy intake and low consumption of foods from animal sources, factors that are hard to study in other populations.

Willett was a coauthor, along with David Ludwig, MD, PhD, also from Harvard, of the recent review published in the New England Journal of Medicine that questioned the science behind milk-drinking recommendations. An article about this review on Medscape Medical News has attracted a huge number of comments from our readers.  

Milk is a complex topic, Willett explained. As a good source of essential nutrients, especially calcium and vitamin D, cow’s milk has been touted to have several health benefits, especially decreased fracture risk. But Willett said calcium recommendations have probably been overstated, and current evidence does not support high milk intake for fracture prevention.

Other benefits include improved nutrition in low-income settings, taller stature, and decreased colorectal cancer risk. But cow’s milk has also been linked to increased risk for some cancers, including prostate and endometrial cancer. Many of the benefits derived from nutrients found in milk may be obtained from other sources without these risks, according to Willett.

“Given the risks and benefits, we suggest a possible range from zero to two servings per day of dairy foods, including milk, cheese, and yogurt. If intake is zero or one serving, taking a calcium/vitamin D supplement would be good to consider,” he said.

However, Fraser and Willett also suggested another option: replacing cow’s milk with soy milk. Analyses from the current study showed no significant association between consumption of soy and breast cancer, independent of dairy (P for trend = .22).

In addition, substituting average amounts of soy milk for cow’s milk was linked to a 32% drop in risk for breast cancer among postmenopausal women (HR, 0.68; 95% CI, 0.55-0.85, P = .002). However, these results were not significant among premenopausal women (HR, 0.70; 95% CI, 0.36-1.38; P = .31).

“The suggestion that replacing some or all of [cow’s] milk with soy milk may reduce risk of breast cancer is consistent with other studies supporting a benefit of soy milk for risk of breast cancer,” Willett said.

“If someone does choose soy milk, picking one with minimal amounts of added sugar is desirable,” he added.

Drinking Milk, or Some Related Factor?

Fraser, the lead author of the current study, said in a statement that the results provide “fairly strong evidence that either dairy milk or some other factor closely related to drinking dairy milk is a cause of breast cancer in women.”

That ‘other’ factor is probably complicated, but may be related to what humans have done to cows. To increase milk production, humans have bred cows to have higher levels of insulin-like growth factor, which in turn has been linked to some cancers, including breast cancer.

Sex hormones in cow’s milk may also be involved. About 75% of a dairy herd is pregnant and the cows are by definition lactating. So the milk they produce may have higher levels of progestins and estrogens, which may play a role in hormone-responsive breast cancer. 

Other factors that researchers did not measure in this study, such as poverty and the income of participants, may be at play.

But to know what’s really going on, all agree that more research is needed.

“The overall evidence so far has not shown a clear increase or decrease in risk of breast cancer with higher [cow’s] milk intake. Thus, this topic needs further examination,” Willett said.

The study was funded by the National Cancer Institute at the National Institutes of Health, and the World Cancer Research Fund in the UK. Three of the authors report following largely vegetarian diets. All authors report regular and free use of dairy products without religious or other restrictions. No authors report associations with the soy product or dairy industries. Willett reports being a consultant during the design and early years of the Adventist study, but has not been involved with it for at least 8 years. Dizon has disclosed no relevant financial relationships.
 

This article first appeared on Medscape.com.

Significant weight gain after a diagnosis of breast cancer may be a bigger problem than previously thought, and clinicians need to do more to help patients manage it, say the authors of a national survey conducted in Australia.

Monkeybusinessimages/Thinkstock

“We found that two-thirds of our respondents were currently overweight or obese,” report Carolyn Ee, MBBS, PhD, of the NICM Health Research Institute, Western Sydney University, Penrith, New South Wales, and colleagues.

“Because weight gain after breast cancer may lead to poorer outcomes, efforts to prevent and manage weight gain must be prioritized and accelerated particularly in the first year after diagnosis,” they comment.

Their article was published online February 20 in BMC Cancer.

The 60-item anonymous online survey was sent to 1835 members of the Breast Cancer Network Australia Review and Survey Group.

Although the response rate for the online survey was only 15%, most women reported a “high” level of concern about weight gain – and with good reason. The results showed that 64% of women gained an average of 9 kg (20 lb), and 17% gained >20 kg (44 lb).

In the 2-year period following a breast cancer diagnosis, the rate of overweight and obesity increased from 48% to 67%. The rate of obesity alone almost doubled, from 17% to 32%.

Overweight and obesity are strongly implicated in the development of breast cancer, the authors note. Weight gain after diagnosis is associated with morbidity and all-cause mortality and may increase the risk for breast cancer recurrence by 30% to 40%.

The survey, which also collected data from 26 women who were participants in online women’s health and breast cancer support groups, did not include information on quality of life and levels of distress. “Additional research in this area appears to be warranted,” the study authors suggest.

In a press statement, Ee noted that 77% of women reported that weight gain had occurred in the 12- to 18-month period after diagnosis. This could provide a “window of opportunity” for intervention, she said.

“Timing may be the key in helping women to manage weight after a diagnosis of breast cancer,” she added. “Cancer services and general practitioners play an important role in having early conversations with women and referring them to a team of qualified healthcare professionals such as dieticians and exercise physiologists with experience in cancer.”

Coauthor John Boyages, MBBS, PhD, a radiation oncologist at the Icon Cancer Center, Sydney Adventist Hospital, Wahroonga, emphasized that all women should be prescribed exercise after being diagnosed with breast cancer. “Prescribing a healthy lifestyle is just as important as prescribing tablets,” he said.

“As doctors, we really need to actively think about weight, nutrition, and exercise and advise about possible interventions. [Among patients with breast cancer,] weight gain adds to self-esteem problems, increases the risk of heart disease and other cancers, and several reports suggest it may affect prognosis and also increases the risk of lymphedema,” he added

“More effort needs to be geared to treating the whole body, as we know obesity is a risk factor for poorer outcomes when dealing with breast cancer,” commented Stephanie Bernik, MD, chief of breast service at Mount Sinai West and associate professor of surgery at the Icahn School of Medicine at Mount Sinai in New York City. She was not involved in the study and was approached for comment.

Berwick also agreed that meeting with a nutritionist or receiving weight loss support is helpful for patients with cancer, but she added that not all cancer centers have the resources to provide these services.
 

Survey Details

Of 309 women who responded to the survey, complete data for pre- and post-diagnosis body mass index (BMI) were collected from 277 respondents, representing 15% of those surveyed.

Of these women, 254 had been diagnosed with stage I-III breast cancer; 33 had been diagnosed with ductal carcinoma in situ. The mean age of the patients was 59 years.

The results showed that for 20% of women, BMI increased from a healthy weight range at the time of diagnosis (BMI <25) to an unhealthy weight range (BMI >25). In addition, for 4.8% of patients, BMI increased from an overweight range (BMI 25 to <30) to obesity (BMI >30), and 60.7% reported an increase in BMI >1 kg/m². Conversely, only a small proportion of women lost weight – 6% experienced a decrease of more than one BMI category.

Weight gain occurred within the first 2 years of diagnosis in 87% of women and within the first 12 months in 58%. In women who gained >10 kg (22 lb), 78% said they were highly concerned about it, as did 59% of women who gained >5 kg (11 lb).

Among all age groups (35 to 74 years), 69% experienced excess weight gain that was 0.48 kg higher each year compared with age-matched control persons who had not been diagnosed with breast cancer. Over 5 years, this represented an additional weight gain of 2 kg (5 lb) among women with breast cancer.

When approached for comment, Bernick agreed with the authors that these results should be interpreted with caution.

She pointed to the self-reporting bias and the fact that only 15% of women responded to the survey. “Perhaps it was only women who had gained weight who found it worthwhile reporting their experience with weight gain after a breast cancer diagnosis,” she suggested.

Even so, there are many reasons why weight gain during treatment for breast cancer presents a problem for women in the United States as well as Australia, Bernik told Medscape Medical News.

“Women undergoing chemotherapy may not have the energy to keep up with exercise regimens and may find eating food comforting,” she pointed out. “Because chemotherapy delivery and the after effects may take up a few days out of every 2 to 3 weeks, women have less time and energy to eat correctly or exercise. Furthermore, women sometimes get steroids while receiving chemotherapy, and this is known to drive up one’s appetite.”

The authors have disclosed no relevant financial relationships.
 

This article first appeared on Medscape.com.

Significant weight gain after a diagnosis of breast cancer may be a bigger problem than previously thought, and clinicians need to do more to help patients manage it, say the authors of a national survey conducted in Australia.

Monkeybusinessimages/Thinkstock

“We found that two-thirds of our respondents were currently overweight or obese,” report Carolyn Ee, MBBS, PhD, of the NICM Health Research Institute, Western Sydney University, Penrith, New South Wales, and colleagues.

“Because weight gain after breast cancer may lead to poorer outcomes, efforts to prevent and manage weight gain must be prioritized and accelerated particularly in the first year after diagnosis,” they comment.

Their article was published online February 20 in BMC Cancer.

The 60-item anonymous online survey was sent to 1835 members of the Breast Cancer Network Australia Review and Survey Group.

Although the response rate for the online survey was only 15%, most women reported a “high” level of concern about weight gain – and with good reason. The results showed that 64% of women gained an average of 9 kg (20 lb), and 17% gained >20 kg (44 lb).

In the 2-year period following a breast cancer diagnosis, the rate of overweight and obesity increased from 48% to 67%. The rate of obesity alone almost doubled, from 17% to 32%.

Overweight and obesity are strongly implicated in the development of breast cancer, the authors note. Weight gain after diagnosis is associated with morbidity and all-cause mortality and may increase the risk for breast cancer recurrence by 30% to 40%.

The survey, which also collected data from 26 women who were participants in online women’s health and breast cancer support groups, did not include information on quality of life and levels of distress. “Additional research in this area appears to be warranted,” the study authors suggest.

In a press statement, Ee noted that 77% of women reported that weight gain had occurred in the 12- to 18-month period after diagnosis. This could provide a “window of opportunity” for intervention, she said.

“Timing may be the key in helping women to manage weight after a diagnosis of breast cancer,” she added. “Cancer services and general practitioners play an important role in having early conversations with women and referring them to a team of qualified healthcare professionals such as dieticians and exercise physiologists with experience in cancer.”

Coauthor John Boyages, MBBS, PhD, a radiation oncologist at the Icon Cancer Center, Sydney Adventist Hospital, Wahroonga, emphasized that all women should be prescribed exercise after being diagnosed with breast cancer. “Prescribing a healthy lifestyle is just as important as prescribing tablets,” he said.

“As doctors, we really need to actively think about weight, nutrition, and exercise and advise about possible interventions. [Among patients with breast cancer,] weight gain adds to self-esteem problems, increases the risk of heart disease and other cancers, and several reports suggest it may affect prognosis and also increases the risk of lymphedema,” he added

“More effort needs to be geared to treating the whole body, as we know obesity is a risk factor for poorer outcomes when dealing with breast cancer,” commented Stephanie Bernik, MD, chief of breast service at Mount Sinai West and associate professor of surgery at the Icahn School of Medicine at Mount Sinai in New York City. She was not involved in the study and was approached for comment.

Berwick also agreed that meeting with a nutritionist or receiving weight loss support is helpful for patients with cancer, but she added that not all cancer centers have the resources to provide these services.
 

Survey Details

Of 309 women who responded to the survey, complete data for pre- and post-diagnosis body mass index (BMI) were collected from 277 respondents, representing 15% of those surveyed.

Of these women, 254 had been diagnosed with stage I-III breast cancer; 33 had been diagnosed with ductal carcinoma in situ. The mean age of the patients was 59 years.

The results showed that for 20% of women, BMI increased from a healthy weight range at the time of diagnosis (BMI <25) to an unhealthy weight range (BMI >25). In addition, for 4.8% of patients, BMI increased from an overweight range (BMI 25 to <30) to obesity (BMI >30), and 60.7% reported an increase in BMI >1 kg/m². Conversely, only a small proportion of women lost weight – 6% experienced a decrease of more than one BMI category.

Weight gain occurred within the first 2 years of diagnosis in 87% of women and within the first 12 months in 58%. In women who gained >10 kg (22 lb), 78% said they were highly concerned about it, as did 59% of women who gained >5 kg (11 lb).

Among all age groups (35 to 74 years), 69% experienced excess weight gain that was 0.48 kg higher each year compared with age-matched control persons who had not been diagnosed with breast cancer. Over 5 years, this represented an additional weight gain of 2 kg (5 lb) among women with breast cancer.

When approached for comment, Bernick agreed with the authors that these results should be interpreted with caution.

She pointed to the self-reporting bias and the fact that only 15% of women responded to the survey. “Perhaps it was only women who had gained weight who found it worthwhile reporting their experience with weight gain after a breast cancer diagnosis,” she suggested.

Even so, there are many reasons why weight gain during treatment for breast cancer presents a problem for women in the United States as well as Australia, Bernik told Medscape Medical News.

“Women undergoing chemotherapy may not have the energy to keep up with exercise regimens and may find eating food comforting,” she pointed out. “Because chemotherapy delivery and the after effects may take up a few days out of every 2 to 3 weeks, women have less time and energy to eat correctly or exercise. Furthermore, women sometimes get steroids while receiving chemotherapy, and this is known to drive up one’s appetite.”

The authors have disclosed no relevant financial relationships.
 

This article first appeared on Medscape.com.

Significant weight gain after a diagnosis of breast cancer may be a bigger problem than previously thought, and clinicians need to do more to help patients manage it, say the authors of a national survey conducted in Australia.

Monkeybusinessimages/Thinkstock

“We found that two-thirds of our respondents were currently overweight or obese,” report Carolyn Ee, MBBS, PhD, of the NICM Health Research Institute, Western Sydney University, Penrith, New South Wales, and colleagues.

“Because weight gain after breast cancer may lead to poorer outcomes, efforts to prevent and manage weight gain must be prioritized and accelerated particularly in the first year after diagnosis,” they comment.

Their article was published online February 20 in BMC Cancer.

The 60-item anonymous online survey was sent to 1835 members of the Breast Cancer Network Australia Review and Survey Group.

Although the response rate for the online survey was only 15%, most women reported a “high” level of concern about weight gain – and with good reason. The results showed that 64% of women gained an average of 9 kg (20 lb), and 17% gained >20 kg (44 lb).

In the 2-year period following a breast cancer diagnosis, the rate of overweight and obesity increased from 48% to 67%. The rate of obesity alone almost doubled, from 17% to 32%.

Overweight and obesity are strongly implicated in the development of breast cancer, the authors note. Weight gain after diagnosis is associated with morbidity and all-cause mortality and may increase the risk for breast cancer recurrence by 30% to 40%.

The survey, which also collected data from 26 women who were participants in online women’s health and breast cancer support groups, did not include information on quality of life and levels of distress. “Additional research in this area appears to be warranted,” the study authors suggest.

In a press statement, Ee noted that 77% of women reported that weight gain had occurred in the 12- to 18-month period after diagnosis. This could provide a “window of opportunity” for intervention, she said.

“Timing may be the key in helping women to manage weight after a diagnosis of breast cancer,” she added. “Cancer services and general practitioners play an important role in having early conversations with women and referring them to a team of qualified healthcare professionals such as dieticians and exercise physiologists with experience in cancer.”

Coauthor John Boyages, MBBS, PhD, a radiation oncologist at the Icon Cancer Center, Sydney Adventist Hospital, Wahroonga, emphasized that all women should be prescribed exercise after being diagnosed with breast cancer. “Prescribing a healthy lifestyle is just as important as prescribing tablets,” he said.

“As doctors, we really need to actively think about weight, nutrition, and exercise and advise about possible interventions. [Among patients with breast cancer,] weight gain adds to self-esteem problems, increases the risk of heart disease and other cancers, and several reports suggest it may affect prognosis and also increases the risk of lymphedema,” he added

“More effort needs to be geared to treating the whole body, as we know obesity is a risk factor for poorer outcomes when dealing with breast cancer,” commented Stephanie Bernik, MD, chief of breast service at Mount Sinai West and associate professor of surgery at the Icahn School of Medicine at Mount Sinai in New York City. She was not involved in the study and was approached for comment.

Berwick also agreed that meeting with a nutritionist or receiving weight loss support is helpful for patients with cancer, but she added that not all cancer centers have the resources to provide these services.
 

Survey Details

Of 309 women who responded to the survey, complete data for pre- and post-diagnosis body mass index (BMI) were collected from 277 respondents, representing 15% of those surveyed.

Of these women, 254 had been diagnosed with stage I-III breast cancer; 33 had been diagnosed with ductal carcinoma in situ. The mean age of the patients was 59 years.

The results showed that for 20% of women, BMI increased from a healthy weight range at the time of diagnosis (BMI <25) to an unhealthy weight range (BMI >25). In addition, for 4.8% of patients, BMI increased from an overweight range (BMI 25 to <30) to obesity (BMI >30), and 60.7% reported an increase in BMI >1 kg/m². Conversely, only a small proportion of women lost weight – 6% experienced a decrease of more than one BMI category.

Weight gain occurred within the first 2 years of diagnosis in 87% of women and within the first 12 months in 58%. In women who gained >10 kg (22 lb), 78% said they were highly concerned about it, as did 59% of women who gained >5 kg (11 lb).

Among all age groups (35 to 74 years), 69% experienced excess weight gain that was 0.48 kg higher each year compared with age-matched control persons who had not been diagnosed with breast cancer. Over 5 years, this represented an additional weight gain of 2 kg (5 lb) among women with breast cancer.

When approached for comment, Bernick agreed with the authors that these results should be interpreted with caution.

She pointed to the self-reporting bias and the fact that only 15% of women responded to the survey. “Perhaps it was only women who had gained weight who found it worthwhile reporting their experience with weight gain after a breast cancer diagnosis,” she suggested.

Even so, there are many reasons why weight gain during treatment for breast cancer presents a problem for women in the United States as well as Australia, Bernik told Medscape Medical News.

“Women undergoing chemotherapy may not have the energy to keep up with exercise regimens and may find eating food comforting,” she pointed out. “Because chemotherapy delivery and the after effects may take up a few days out of every 2 to 3 weeks, women have less time and energy to eat correctly or exercise. Furthermore, women sometimes get steroids while receiving chemotherapy, and this is known to drive up one’s appetite.”

The authors have disclosed no relevant financial relationships.
 

This article first appeared on Medscape.com.

For women with dense breasts, abbreviated magnetic resonance imaging was more effective than was digital breast tomosynthesis for detecting invasive breast cancer in a cross-sectional study of 1,444 women who underwent both procedures.

Dense breasts are a common reason for failed early diagnosis of breast cancer, wrote Christopher E. Comstock, MD, of Memorial Sloan Kettering Cancer Center, New York, and colleagues. Digital breast tomosynthesis (DBT) and abbreviated breast magnetic resonance imaging (MRI) are becoming more popular as safe and cost-effective breast cancer screening options, but their effectiveness in women with dense breasts and average breast cancer risk has not been compared.

The researchers reviewed data from 1,444 women aged 40-75 years at 47 institutions in the United States and 1 in Germany. The women underwent both DBT and MRI. The primary endpoint was the detection of invasive cancers, of which 17 were identified at baseline screening. Abbreviated breast MRI detected all 17 cases of invasive cancer, compared with 7 detected by DBT. In addition, MRI detected six of seven women with ductal carcinoma in situ, while DBT identified two of the seven cases, according to the study, which was published in JAMA.

Overall, the invasive cancer detection rate was 11.8 per 1,000 women for MRI compared with 4.8 per 1,000 women for DBT. Sensitivity for MRI and DBT was 96% vs. 39%, and specificity was 87% vs. 97%.

The rate of recommendation for further screening was not significantly different between the procedures (8% for MRI and 10% for DBT). The most common adverse events were three cases of mild allergic reactions and two cases of anxiety.

The study findings were limited by several factors including the inability to show an association between abbreviated breast MRI and breast cancer mortality and the lack of cost-effectiveness comparisons for the two procedures. Because eligibility criteria required a prior breast mammogram to see if the breasts were dense, the study compared an incidence DBT screen to a prevalence abbreviated MRI screen, Dr. Comstock and associates noted.

However, the results show a significantly increased breast cancer detection rate with abbreviated MRI, which merits additional research to examine the relationship between screening strategies and clinical outcomes for women with dense breasts, they said.

The study was supported in part by the National Cancer Institute of the National Institutes of Health, and by Bracco Diagnostics through funding to the ECOG-ACRIN Cancer Research Group. Dr. Comstock disclosed financial relationships with Bracco Diagnostics and Bayer, and three coauthors disclosed financial relationships with other imaging companies. The remaining coauthors had no relevant financial disclosures.
 

SOURCE: Comstock CK et al. JAMA. 2020 Feb 25. doi: 10.1001/jama.2020.0572.

For women with dense breasts, abbreviated magnetic resonance imaging was more effective than was digital breast tomosynthesis for detecting invasive breast cancer in a cross-sectional study of 1,444 women who underwent both procedures.

Dense breasts are a common reason for failed early diagnosis of breast cancer, wrote Christopher E. Comstock, MD, of Memorial Sloan Kettering Cancer Center, New York, and colleagues. Digital breast tomosynthesis (DBT) and abbreviated breast magnetic resonance imaging (MRI) are becoming more popular as safe and cost-effective breast cancer screening options, but their effectiveness in women with dense breasts and average breast cancer risk has not been compared.

The researchers reviewed data from 1,444 women aged 40-75 years at 47 institutions in the United States and 1 in Germany. The women underwent both DBT and MRI. The primary endpoint was the detection of invasive cancers, of which 17 were identified at baseline screening. Abbreviated breast MRI detected all 17 cases of invasive cancer, compared with 7 detected by DBT. In addition, MRI detected six of seven women with ductal carcinoma in situ, while DBT identified two of the seven cases, according to the study, which was published in JAMA.

Overall, the invasive cancer detection rate was 11.8 per 1,000 women for MRI compared with 4.8 per 1,000 women for DBT. Sensitivity for MRI and DBT was 96% vs. 39%, and specificity was 87% vs. 97%.

The rate of recommendation for further screening was not significantly different between the procedures (8% for MRI and 10% for DBT). The most common adverse events were three cases of mild allergic reactions and two cases of anxiety.

The study findings were limited by several factors including the inability to show an association between abbreviated breast MRI and breast cancer mortality and the lack of cost-effectiveness comparisons for the two procedures. Because eligibility criteria required a prior breast mammogram to see if the breasts were dense, the study compared an incidence DBT screen to a prevalence abbreviated MRI screen, Dr. Comstock and associates noted.

However, the results show a significantly increased breast cancer detection rate with abbreviated MRI, which merits additional research to examine the relationship between screening strategies and clinical outcomes for women with dense breasts, they said.

The study was supported in part by the National Cancer Institute of the National Institutes of Health, and by Bracco Diagnostics through funding to the ECOG-ACRIN Cancer Research Group. Dr. Comstock disclosed financial relationships with Bracco Diagnostics and Bayer, and three coauthors disclosed financial relationships with other imaging companies. The remaining coauthors had no relevant financial disclosures.
 

SOURCE: Comstock CK et al. JAMA. 2020 Feb 25. doi: 10.1001/jama.2020.0572.

For women with dense breasts, abbreviated magnetic resonance imaging was more effective than was digital breast tomosynthesis for detecting invasive breast cancer in a cross-sectional study of 1,444 women who underwent both procedures.

Dense breasts are a common reason for failed early diagnosis of breast cancer, wrote Christopher E. Comstock, MD, of Memorial Sloan Kettering Cancer Center, New York, and colleagues. Digital breast tomosynthesis (DBT) and abbreviated breast magnetic resonance imaging (MRI) are becoming more popular as safe and cost-effective breast cancer screening options, but their effectiveness in women with dense breasts and average breast cancer risk has not been compared.

The researchers reviewed data from 1,444 women aged 40-75 years at 47 institutions in the United States and 1 in Germany. The women underwent both DBT and MRI. The primary endpoint was the detection of invasive cancers, of which 17 were identified at baseline screening. Abbreviated breast MRI detected all 17 cases of invasive cancer, compared with 7 detected by DBT. In addition, MRI detected six of seven women with ductal carcinoma in situ, while DBT identified two of the seven cases, according to the study, which was published in JAMA.

Overall, the invasive cancer detection rate was 11.8 per 1,000 women for MRI compared with 4.8 per 1,000 women for DBT. Sensitivity for MRI and DBT was 96% vs. 39%, and specificity was 87% vs. 97%.

The rate of recommendation for further screening was not significantly different between the procedures (8% for MRI and 10% for DBT). The most common adverse events were three cases of mild allergic reactions and two cases of anxiety.

The study findings were limited by several factors including the inability to show an association between abbreviated breast MRI and breast cancer mortality and the lack of cost-effectiveness comparisons for the two procedures. Because eligibility criteria required a prior breast mammogram to see if the breasts were dense, the study compared an incidence DBT screen to a prevalence abbreviated MRI screen, Dr. Comstock and associates noted.

However, the results show a significantly increased breast cancer detection rate with abbreviated MRI, which merits additional research to examine the relationship between screening strategies and clinical outcomes for women with dense breasts, they said.

The study was supported in part by the National Cancer Institute of the National Institutes of Health, and by Bracco Diagnostics through funding to the ECOG-ACRIN Cancer Research Group. Dr. Comstock disclosed financial relationships with Bracco Diagnostics and Bayer, and three coauthors disclosed financial relationships with other imaging companies. The remaining coauthors had no relevant financial disclosures.
 

SOURCE: Comstock CK et al. JAMA. 2020 Feb 25. doi: 10.1001/jama.2020.0572.

The Food and Drug Administration has approved neratinib (NERLYNX) in combination with capecitabine for use in adults with advanced or metastatic HER2-positive breast cancer who have received at least two prior anti-HER2 based regimens in the metastatic setting.

The recommended dose for neratinib in this population is 240 mg once daily with food on days 1-21 of a 21-day cycle. Neratinib should be given with capecitabine at 750 mg/m² twice daily on days 1-14 until progression or unacceptable toxicity.

The full prescribing information for neratinib is available from the FDA website.

The FDA’s new approval of neratinib is based on results from the NALA trial (NCT01808573). The trial enrolled 621 patients with metastatic HER2-positive breast cancer who had received at least two prior anti-HER2 based regimens in the metastatic setting.

The patients were randomized to neratinib plus capecitabine or lapatinib plus capecitabine and received treatment until progression or unacceptable toxicity.

The objective response rate was 32.8% in the neratinib arm and 26.7% in the lapatinib arm. The median duration of response was 8.5 months and 5.6 months, respectively.

The median progression-free survival was 5.6 months in the neratinib arm and 5.5 months in the lapatinib arm (hazard ratio 0.76; P = .0059). The median overall survival was 21 months and 18.7 months, respectively (HR 0.88; P = .2086).

The most common grade 3/4 adverse events in the neratinib arm were diarrhea, nausea, vomiting, fatigue, and decreased appetite.

jensmith@mdedge.com

The Food and Drug Administration has approved neratinib (NERLYNX) in combination with capecitabine for use in adults with advanced or metastatic HER2-positive breast cancer who have received at least two prior anti-HER2 based regimens in the metastatic setting.

The recommended dose for neratinib in this population is 240 mg once daily with food on days 1-21 of a 21-day cycle. Neratinib should be given with capecitabine at 750 mg/m² twice daily on days 1-14 until progression or unacceptable toxicity.

The full prescribing information for neratinib is available from the FDA website.

The FDA’s new approval of neratinib is based on results from the NALA trial (NCT01808573). The trial enrolled 621 patients with metastatic HER2-positive breast cancer who had received at least two prior anti-HER2 based regimens in the metastatic setting.

The patients were randomized to neratinib plus capecitabine or lapatinib plus capecitabine and received treatment until progression or unacceptable toxicity.

The objective response rate was 32.8% in the neratinib arm and 26.7% in the lapatinib arm. The median duration of response was 8.5 months and 5.6 months, respectively.

The median progression-free survival was 5.6 months in the neratinib arm and 5.5 months in the lapatinib arm (hazard ratio 0.76; P = .0059). The median overall survival was 21 months and 18.7 months, respectively (HR 0.88; P = .2086).

The most common grade 3/4 adverse events in the neratinib arm were diarrhea, nausea, vomiting, fatigue, and decreased appetite.

jensmith@mdedge.com

The Food and Drug Administration has approved neratinib (NERLYNX) in combination with capecitabine for use in adults with advanced or metastatic HER2-positive breast cancer who have received at least two prior anti-HER2 based regimens in the metastatic setting.

The recommended dose for neratinib in this population is 240 mg once daily with food on days 1-21 of a 21-day cycle. Neratinib should be given with capecitabine at 750 mg/m² twice daily on days 1-14 until progression or unacceptable toxicity.

The full prescribing information for neratinib is available from the FDA website.

The FDA’s new approval of neratinib is based on results from the NALA trial (NCT01808573). The trial enrolled 621 patients with metastatic HER2-positive breast cancer who had received at least two prior anti-HER2 based regimens in the metastatic setting.

The patients were randomized to neratinib plus capecitabine or lapatinib plus capecitabine and received treatment until progression or unacceptable toxicity.

The objective response rate was 32.8% in the neratinib arm and 26.7% in the lapatinib arm. The median duration of response was 8.5 months and 5.6 months, respectively.

The median progression-free survival was 5.6 months in the neratinib arm and 5.5 months in the lapatinib arm (hazard ratio 0.76; P = .0059). The median overall survival was 21 months and 18.7 months, respectively (HR 0.88; P = .2086).

The most common grade 3/4 adverse events in the neratinib arm were diarrhea, nausea, vomiting, fatigue, and decreased appetite.

jensmith@mdedge.com

Cancer patients in states that opted to expand Medicaid insurance coverage under the Affordable Care Act saw a slightly better rate of early diagnosis, compared with patients in states that refused expansion, according to a new study. However, time to treatment was similar in states that opted for expansion and states that did not.

Samuel U. Takvorian, MD, of the University of Pennsylvania, Philadelphia, and colleagues reported these results in JAMA Network Open.

The researchers used the National Cancer Database to examine the changes in health insurance coverage and cancer health outcomes in nonelderly patients following implementation of the Affordable Care Act in January 2014. The investigators identified records for 925,543 patients who had new-onset breast (59%), colon (15%), or non–small cell lung (27%) cancer between 2011 and 2016. The patients’ mean age was 55 years (range, 40-64 years), 79% were women, 14% were black, and 6% were Hispanic.

The researchers looked at insurance status, cancer stage at diagnosis, and treatment initiation within 30 and 90 days of diagnosis. The cohort was equally divided between residents of Medicaid expansion states (48%) and nonexpansion states (52%).

Using a statistical technique that mimics a controlled experiment, the investigators found the percentage of uninsured patients decreased more in the expansion states (adjusted difference-in-differences, −0.7 percentage points; 95% confidence interval, −1.2 to −0.3; P = .001), compared with nonexpansion states. Expansion states also had a greater increase in early-stage cancer diagnoses (adjusted DID, 0.8; 95% CI 0.3-1.2; P = .001) and a greater decrease in advanced-stage cancer diagnoses (adjusted DID, −0.5; 95% CI, −0.9 to −0.2; P = .003).

Among the 848,329 patients who underwent cancer treatment within a year of diagnosis, the percentage initiating treatment within 30 days declined from 52.7% before to 48% after Medicaid expansion in states opting in (unadjusted DID, −4.7; percentage points, 95% CI; −5.1 to −4.5). States that did not expand their Medicaid programs, meanwhile, saw the share decline from 56.9% to 51.5% in the same time period (adjusted DID, −5.4; 95% CI, −5.6 to −5.1). There was no statistically significant difference in timely treatment associated with Medicaid expansion (adjusted DID, 0.6; 95% CI, −0.2 to 1.4; P = .14).

The researchers speculated that the lack of significant between-group differences in time to treatment, despite an improvement in early-stage diagnoses associated with Medicaid expansion, could reflect a cancer care system strained by a surge in insured patients, overall increases in cancer prevalence and complexity of care, a shortage of workers, or a mixture of factors.

In a related editorial, Sue Fu, MD, of Stanford (Calif.) University, and colleagues wrote that, while the findings of increased early diagnosis seen in the study are promising, the time to treatment results are “puzzling” and deserve further consideration.

Time to treatment is important in cancer, as longer times are associated with increased mortality, Dr. Fu and colleagues noted. Slowing times to cancer treatment is a systemic problem in the United States that has been documented since the mid-2000s. Paradoxically, expanded insurance coverage could contribute to increasing time to treatment even after timely diagnosis by adding administrative burdens leading to longer wait times. “Newly insured and underinsured individuals may be particularly vulnerable to this,” the editorialists wrote.

Dr. Takvorian and colleagues noted as weaknesses of their study its observational design, a limited range of ages and cancers included, and an inability to adjust for state-level effects.

This study was funded by the National Cancer Institute and the Agency for Health Research and Quality. The authors of the study and the editorial disclosed no relevant conflicts of interest.

SOURCES: Takvorian SU et al. JAMA Netw Open. 2020 Feb 5;3(2):e1921653; Fu S et al. JAMA Netw Open. 2020 Feb 5;3(2):e1921690.

Cancer patients in states that opted to expand Medicaid insurance coverage under the Affordable Care Act saw a slightly better rate of early diagnosis, compared with patients in states that refused expansion, according to a new study. However, time to treatment was similar in states that opted for expansion and states that did not.

Samuel U. Takvorian, MD, of the University of Pennsylvania, Philadelphia, and colleagues reported these results in JAMA Network Open.

The researchers used the National Cancer Database to examine the changes in health insurance coverage and cancer health outcomes in nonelderly patients following implementation of the Affordable Care Act in January 2014. The investigators identified records for 925,543 patients who had new-onset breast (59%), colon (15%), or non–small cell lung (27%) cancer between 2011 and 2016. The patients’ mean age was 55 years (range, 40-64 years), 79% were women, 14% were black, and 6% were Hispanic.

The researchers looked at insurance status, cancer stage at diagnosis, and treatment initiation within 30 and 90 days of diagnosis. The cohort was equally divided between residents of Medicaid expansion states (48%) and nonexpansion states (52%).

Using a statistical technique that mimics a controlled experiment, the investigators found the percentage of uninsured patients decreased more in the expansion states (adjusted difference-in-differences, −0.7 percentage points; 95% confidence interval, −1.2 to −0.3; P = .001), compared with nonexpansion states. Expansion states also had a greater increase in early-stage cancer diagnoses (adjusted DID, 0.8; 95% CI 0.3-1.2; P = .001) and a greater decrease in advanced-stage cancer diagnoses (adjusted DID, −0.5; 95% CI, −0.9 to −0.2; P = .003).

Among the 848,329 patients who underwent cancer treatment within a year of diagnosis, the percentage initiating treatment within 30 days declined from 52.7% before to 48% after Medicaid expansion in states opting in (unadjusted DID, −4.7; percentage points, 95% CI; −5.1 to −4.5). States that did not expand their Medicaid programs, meanwhile, saw the share decline from 56.9% to 51.5% in the same time period (adjusted DID, −5.4; 95% CI, −5.6 to −5.1). There was no statistically significant difference in timely treatment associated with Medicaid expansion (adjusted DID, 0.6; 95% CI, −0.2 to 1.4; P = .14).

The researchers speculated that the lack of significant between-group differences in time to treatment, despite an improvement in early-stage diagnoses associated with Medicaid expansion, could reflect a cancer care system strained by a surge in insured patients, overall increases in cancer prevalence and complexity of care, a shortage of workers, or a mixture of factors.

In a related editorial, Sue Fu, MD, of Stanford (Calif.) University, and colleagues wrote that, while the findings of increased early diagnosis seen in the study are promising, the time to treatment results are “puzzling” and deserve further consideration.

Time to treatment is important in cancer, as longer times are associated with increased mortality, Dr. Fu and colleagues noted. Slowing times to cancer treatment is a systemic problem in the United States that has been documented since the mid-2000s. Paradoxically, expanded insurance coverage could contribute to increasing time to treatment even after timely diagnosis by adding administrative burdens leading to longer wait times. “Newly insured and underinsured individuals may be particularly vulnerable to this,” the editorialists wrote.

Dr. Takvorian and colleagues noted as weaknesses of their study its observational design, a limited range of ages and cancers included, and an inability to adjust for state-level effects.

This study was funded by the National Cancer Institute and the Agency for Health Research and Quality. The authors of the study and the editorial disclosed no relevant conflicts of interest.

SOURCES: Takvorian SU et al. JAMA Netw Open. 2020 Feb 5;3(2):e1921653; Fu S et al. JAMA Netw Open. 2020 Feb 5;3(2):e1921690.

Cancer patients in states that opted to expand Medicaid insurance coverage under the Affordable Care Act saw a slightly better rate of early diagnosis, compared with patients in states that refused expansion, according to a new study. However, time to treatment was similar in states that opted for expansion and states that did not.

Samuel U. Takvorian, MD, of the University of Pennsylvania, Philadelphia, and colleagues reported these results in JAMA Network Open.

The researchers used the National Cancer Database to examine the changes in health insurance coverage and cancer health outcomes in nonelderly patients following implementation of the Affordable Care Act in January 2014. The investigators identified records for 925,543 patients who had new-onset breast (59%), colon (15%), or non–small cell lung (27%) cancer between 2011 and 2016. The patients’ mean age was 55 years (range, 40-64 years), 79% were women, 14% were black, and 6% were Hispanic.

The researchers looked at insurance status, cancer stage at diagnosis, and treatment initiation within 30 and 90 days of diagnosis. The cohort was equally divided between residents of Medicaid expansion states (48%) and nonexpansion states (52%).

Using a statistical technique that mimics a controlled experiment, the investigators found the percentage of uninsured patients decreased more in the expansion states (adjusted difference-in-differences, −0.7 percentage points; 95% confidence interval, −1.2 to −0.3; P = .001), compared with nonexpansion states. Expansion states also had a greater increase in early-stage cancer diagnoses (adjusted DID, 0.8; 95% CI 0.3-1.2; P = .001) and a greater decrease in advanced-stage cancer diagnoses (adjusted DID, −0.5; 95% CI, −0.9 to −0.2; P = .003).

Among the 848,329 patients who underwent cancer treatment within a year of diagnosis, the percentage initiating treatment within 30 days declined from 52.7% before to 48% after Medicaid expansion in states opting in (unadjusted DID, −4.7; percentage points, 95% CI; −5.1 to −4.5). States that did not expand their Medicaid programs, meanwhile, saw the share decline from 56.9% to 51.5% in the same time period (adjusted DID, −5.4; 95% CI, −5.6 to −5.1). There was no statistically significant difference in timely treatment associated with Medicaid expansion (adjusted DID, 0.6; 95% CI, −0.2 to 1.4; P = .14).

The researchers speculated that the lack of significant between-group differences in time to treatment, despite an improvement in early-stage diagnoses associated with Medicaid expansion, could reflect a cancer care system strained by a surge in insured patients, overall increases in cancer prevalence and complexity of care, a shortage of workers, or a mixture of factors.

In a related editorial, Sue Fu, MD, of Stanford (Calif.) University, and colleagues wrote that, while the findings of increased early diagnosis seen in the study are promising, the time to treatment results are “puzzling” and deserve further consideration.

Time to treatment is important in cancer, as longer times are associated with increased mortality, Dr. Fu and colleagues noted. Slowing times to cancer treatment is a systemic problem in the United States that has been documented since the mid-2000s. Paradoxically, expanded insurance coverage could contribute to increasing time to treatment even after timely diagnosis by adding administrative burdens leading to longer wait times. “Newly insured and underinsured individuals may be particularly vulnerable to this,” the editorialists wrote.

Dr. Takvorian and colleagues noted as weaknesses of their study its observational design, a limited range of ages and cancers included, and an inability to adjust for state-level effects.

This study was funded by the National Cancer Institute and the Agency for Health Research and Quality. The authors of the study and the editorial disclosed no relevant conflicts of interest.

SOURCES: Takvorian SU et al. JAMA Netw Open. 2020 Feb 5;3(2):e1921653; Fu S et al. JAMA Netw Open. 2020 Feb 5;3(2):e1921690.

The topoisomerase I (TOP1) inhibitor irinotecan could be effective in treating triple-negative breast cancer (TNBC), according to results from a preclinical study published in Science Translational Medicine.

Florence Coussy, MD, PhD, of Institut Curie, Paris, and colleagues evaluated the antitumor activity of the Food and Drug Administration–approved TOP1 inhibitor irinotecan in 40 patient-derived xenografts (PDXs) of TNBC.

Other treatments, such as noncamptothecin TOP1 inhibitors (indotecan and indimitecan) and irinotecan plus VE-822 (an ataxia telangiectasia and Rad3-related protein [ATR] inhibitor), were also evaluated in the PDX models.

Tumor samples were collected from patients with primary breast cancer at the time of surgery (55%), residual breast cancer after neoadjuvant treatment (40%), or axillary lymph node metastases (5%). The patients had a mean age of 56 years (range, 29-89 years).

The researchers assessed BRCAness using the homologous recombination deficiency–large-scale state transition assay. Additional potential markers of response, including expression of retinoblastoma transcriptional corepressor 1 (RB1) and Schlafen family member 11 (SLFN11), were detected on transcriptomic analysis and validated using immunohistochemistry analyses.

The researchers found that 37.5% (n = 15) of TNBC PDX models achieved a partial or complete response to irinotecan therapy, while 22.5% (n = 9) of models had stable disease. BRCAness, RB1 loss, and high SLFN11 expression were deemed potential markers of response to irinotecan and other clinical TOP1 inhibitors.

The researchers then evaluated 250 breast cancer patients treated with anthracycline-based chemotherapy and found that lower expression of SLFN11 was associated with worse survival.

“We also [found] that, in the absence of SLFN11, response to irinotecan can be increased by adding an ATR inhibitor and that the clinical TOP1 inhibitors are highly efficient in BRCA1-mutant and BRCAness-positive TNBC PDXs,” the researchers reported.

They acknowledged that a key limitation of this study was the absence of tumor samples from patients who had received a TOP1 inhibitor.

“Overall, our findings are in line with the notion that concomitant defects in DNA repair and checkpoints render cancer cells highly vulnerable to TOP1 inhibitors,” the researchers concluded.

The study was funded by the National Cancer Institute, PIC3i NCI-Curie, and Site de Recherche Intégrée sur le Cancer. One author is an inventor of indotecan and indimitecan. Two authors are coinventors of the method used to detect inactivation of the homologous recombination pathway, which is licensed to Myriad Genetics.

SOURCE: Coussy F et al. Sci Transl Med. 2020 Feb 19. doi: 10.1126/scitranslmed.aax2625.

The topoisomerase I (TOP1) inhibitor irinotecan could be effective in treating triple-negative breast cancer (TNBC), according to results from a preclinical study published in Science Translational Medicine.

Florence Coussy, MD, PhD, of Institut Curie, Paris, and colleagues evaluated the antitumor activity of the Food and Drug Administration–approved TOP1 inhibitor irinotecan in 40 patient-derived xenografts (PDXs) of TNBC.

Other treatments, such as noncamptothecin TOP1 inhibitors (indotecan and indimitecan) and irinotecan plus VE-822 (an ataxia telangiectasia and Rad3-related protein [ATR] inhibitor), were also evaluated in the PDX models.

Tumor samples were collected from patients with primary breast cancer at the time of surgery (55%), residual breast cancer after neoadjuvant treatment (40%), or axillary lymph node metastases (5%). The patients had a mean age of 56 years (range, 29-89 years).

The researchers assessed BRCAness using the homologous recombination deficiency–large-scale state transition assay. Additional potential markers of response, including expression of retinoblastoma transcriptional corepressor 1 (RB1) and Schlafen family member 11 (SLFN11), were detected on transcriptomic analysis and validated using immunohistochemistry analyses.

The researchers found that 37.5% (n = 15) of TNBC PDX models achieved a partial or complete response to irinotecan therapy, while 22.5% (n = 9) of models had stable disease. BRCAness, RB1 loss, and high SLFN11 expression were deemed potential markers of response to irinotecan and other clinical TOP1 inhibitors.

The researchers then evaluated 250 breast cancer patients treated with anthracycline-based chemotherapy and found that lower expression of SLFN11 was associated with worse survival.

“We also [found] that, in the absence of SLFN11, response to irinotecan can be increased by adding an ATR inhibitor and that the clinical TOP1 inhibitors are highly efficient in BRCA1-mutant and BRCAness-positive TNBC PDXs,” the researchers reported.

They acknowledged that a key limitation of this study was the absence of tumor samples from patients who had received a TOP1 inhibitor.

“Overall, our findings are in line with the notion that concomitant defects in DNA repair and checkpoints render cancer cells highly vulnerable to TOP1 inhibitors,” the researchers concluded.

The study was funded by the National Cancer Institute, PIC3i NCI-Curie, and Site de Recherche Intégrée sur le Cancer. One author is an inventor of indotecan and indimitecan. Two authors are coinventors of the method used to detect inactivation of the homologous recombination pathway, which is licensed to Myriad Genetics.

SOURCE: Coussy F et al. Sci Transl Med. 2020 Feb 19. doi: 10.1126/scitranslmed.aax2625.

The topoisomerase I (TOP1) inhibitor irinotecan could be effective in treating triple-negative breast cancer (TNBC), according to results from a preclinical study published in Science Translational Medicine.

Florence Coussy, MD, PhD, of Institut Curie, Paris, and colleagues evaluated the antitumor activity of the Food and Drug Administration–approved TOP1 inhibitor irinotecan in 40 patient-derived xenografts (PDXs) of TNBC.

Other treatments, such as noncamptothecin TOP1 inhibitors (indotecan and indimitecan) and irinotecan plus VE-822 (an ataxia telangiectasia and Rad3-related protein [ATR] inhibitor), were also evaluated in the PDX models.

Tumor samples were collected from patients with primary breast cancer at the time of surgery (55%), residual breast cancer after neoadjuvant treatment (40%), or axillary lymph node metastases (5%). The patients had a mean age of 56 years (range, 29-89 years).

The researchers assessed BRCAness using the homologous recombination deficiency–large-scale state transition assay. Additional potential markers of response, including expression of retinoblastoma transcriptional corepressor 1 (RB1) and Schlafen family member 11 (SLFN11), were detected on transcriptomic analysis and validated using immunohistochemistry analyses.

The researchers found that 37.5% (n = 15) of TNBC PDX models achieved a partial or complete response to irinotecan therapy, while 22.5% (n = 9) of models had stable disease. BRCAness, RB1 loss, and high SLFN11 expression were deemed potential markers of response to irinotecan and other clinical TOP1 inhibitors.

The researchers then evaluated 250 breast cancer patients treated with anthracycline-based chemotherapy and found that lower expression of SLFN11 was associated with worse survival.

“We also [found] that, in the absence of SLFN11, response to irinotecan can be increased by adding an ATR inhibitor and that the clinical TOP1 inhibitors are highly efficient in BRCA1-mutant and BRCAness-positive TNBC PDXs,” the researchers reported.

They acknowledged that a key limitation of this study was the absence of tumor samples from patients who had received a TOP1 inhibitor.

“Overall, our findings are in line with the notion that concomitant defects in DNA repair and checkpoints render cancer cells highly vulnerable to TOP1 inhibitors,” the researchers concluded.

The study was funded by the National Cancer Institute, PIC3i NCI-Curie, and Site de Recherche Intégrée sur le Cancer. One author is an inventor of indotecan and indimitecan. Two authors are coinventors of the method used to detect inactivation of the homologous recombination pathway, which is licensed to Myriad Genetics.

SOURCE: Coussy F et al. Sci Transl Med. 2020 Feb 19. doi: 10.1126/scitranslmed.aax2625.

The first trial of robot-assisted, high-precision supermicrosurgery in humans has shown that the technique was safe for treating breast cancer–related lymphedema.

Although results were preliminary – only 20 patients participated, and a single highly skilled surgeon performed the supermicrosurgery – additional trials are underway to test the new robotic technique at other centers.

The pilot study was published online Feb. 11 in Nature Communications.

The new device, known as MUSA, was supplied by MicroSure.

MUSA allowed surgeons to connect tiny vessels, as small as 0.3-0.8 mm across, a technique referred to as supermicrosurgery. This technique can be used to connect blocked lymph vessels to veins, which can reestablish flow of lymphatic fluid and decrease arm swelling in women with breast cancer–related lymphedema, the researchers explain.

Only a few highly skilled surgeons worldwide can conduct supermicrosurgery using current surgical techniques, the authors comment.

“The success of supermicrosurgery is limited by the precision and stability of the surgeon’s hands. Robot-assisted supermicrosurgery has the potential to overcome this obstacle because more refined and subtle movements can be performed. Before now, no robots were able to perform this type of surgery,” coauthor Rutger M. Schols, MD, PhD, of Maastricht (the Netherlands) University Medical Center, said in an interview.

Robot-assisted surgery is not new – the Da Vinci system was the first robotic surgery device to be approved by the Food and Drug Administration. It was approved in 2000. However, Da Vinci was developed for minimally invasive surgery and is not precise enough for supermicrosurgery. And despite its $2 million price tag, Da Vinci has yet to show that it performs better than traditional surgery.

Designed specifically for supermicrosurgery

The MUSA robot was designed by surgeons at the Maastricht University Medical Center, engineers at the Eindhoven University of Technology, and the medical technology company Microsure specifically for reconstructive supermicrosurgery; all are located in the Netherlands. Two of the authors of the article hold positions and are shareholders in the company.

Surgeons activate MUSA using foot pedals and operate forceps-like joysticks to control high-precision surgical instruments that filter out hand tremors and scale down motions. For example, moving the joystick 1 cm causes the robot to move 0.10 mm. MUSA also works with standard microscopes found in most operating rooms.

To test MUSA, Dr. Schols and colleagues conducted a prospective, randomized trial that included 20 women with breast cancer–related lymphedema. The team randomly assigned eight women to undergo supermicrosurgery with MUSA and 12 women to undergo manual supermicrosurgery performed by a single surgeon. Two microsurgeons who were blinded to treatment groups evaluated the quality of the surgery using standardized scoring methods.

The results, which were adjusted for baseline factors, showed no significant differences in upper-limb lymphedema between the two groups 1 and 3 months after surgery, nor were there significant differences between the two groups in quality of life.

A slightly higher percentage of women in the MUSA group were able to discontinue daily use of a compressive garment to treat arm swelling at 3 months, compared with the group that underwent manual supermicrosurgery (87.5% vs. 83.3%). Participants reported no serious adverse events.

For the group that underwent manual surgery, the quality of anastomosis was significantly better, compared with the MUSA group. Surgical competency also was significantly higher in the group that underwent manual surgery.

The MUSA group experienced a longer total surgery time (mean, 115 min), compared with the group that underwent manual surgery (mean, 81 min). But the authors note that duration of surgery declined steeply over time for the MUSA group, suggesting a learning curve in using the robot.

The researchers caution that the study may have been too small to detect significant differences between groups. Larger studies are needed to test MUSA with other surgeons operating in other centers, the authors note.

“With respect to treatment of breast cancer–related lymphedema, we are continuing trials with more patients, more surgeons, and more centers,” Dr. Schols said in an interview.

“We expect that other centers – both national and international – are willing to test the MUSA,” he added.

Dr. Schols and several coauthors have disclosed no relevant financial relationships. Two coauthors are shareholders and hold positions at MicroSure.
 

This article first appeared on Medscape.com.

The first trial of robot-assisted, high-precision supermicrosurgery in humans has shown that the technique was safe for treating breast cancer–related lymphedema.

Although results were preliminary – only 20 patients participated, and a single highly skilled surgeon performed the supermicrosurgery – additional trials are underway to test the new robotic technique at other centers.

The pilot study was published online Feb. 11 in Nature Communications.

The new device, known as MUSA, was supplied by MicroSure.

MUSA allowed surgeons to connect tiny vessels, as small as 0.3-0.8 mm across, a technique referred to as supermicrosurgery. This technique can be used to connect blocked lymph vessels to veins, which can reestablish flow of lymphatic fluid and decrease arm swelling in women with breast cancer–related lymphedema, the researchers explain.

Only a few highly skilled surgeons worldwide can conduct supermicrosurgery using current surgical techniques, the authors comment.

“The success of supermicrosurgery is limited by the precision and stability of the surgeon’s hands. Robot-assisted supermicrosurgery has the potential to overcome this obstacle because more refined and subtle movements can be performed. Before now, no robots were able to perform this type of surgery,” coauthor Rutger M. Schols, MD, PhD, of Maastricht (the Netherlands) University Medical Center, said in an interview.

Robot-assisted surgery is not new – the Da Vinci system was the first robotic surgery device to be approved by the Food and Drug Administration. It was approved in 2000. However, Da Vinci was developed for minimally invasive surgery and is not precise enough for supermicrosurgery. And despite its $2 million price tag, Da Vinci has yet to show that it performs better than traditional surgery.

Designed specifically for supermicrosurgery

The MUSA robot was designed by surgeons at the Maastricht University Medical Center, engineers at the Eindhoven University of Technology, and the medical technology company Microsure specifically for reconstructive supermicrosurgery; all are located in the Netherlands. Two of the authors of the article hold positions and are shareholders in the company.

Surgeons activate MUSA using foot pedals and operate forceps-like joysticks to control high-precision surgical instruments that filter out hand tremors and scale down motions. For example, moving the joystick 1 cm causes the robot to move 0.10 mm. MUSA also works with standard microscopes found in most operating rooms.

To test MUSA, Dr. Schols and colleagues conducted a prospective, randomized trial that included 20 women with breast cancer–related lymphedema. The team randomly assigned eight women to undergo supermicrosurgery with MUSA and 12 women to undergo manual supermicrosurgery performed by a single surgeon. Two microsurgeons who were blinded to treatment groups evaluated the quality of the surgery using standardized scoring methods.

The results, which were adjusted for baseline factors, showed no significant differences in upper-limb lymphedema between the two groups 1 and 3 months after surgery, nor were there significant differences between the two groups in quality of life.

A slightly higher percentage of women in the MUSA group were able to discontinue daily use of a compressive garment to treat arm swelling at 3 months, compared with the group that underwent manual supermicrosurgery (87.5% vs. 83.3%). Participants reported no serious adverse events.

For the group that underwent manual surgery, the quality of anastomosis was significantly better, compared with the MUSA group. Surgical competency also was significantly higher in the group that underwent manual surgery.

The MUSA group experienced a longer total surgery time (mean, 115 min), compared with the group that underwent manual surgery (mean, 81 min). But the authors note that duration of surgery declined steeply over time for the MUSA group, suggesting a learning curve in using the robot.

The researchers caution that the study may have been too small to detect significant differences between groups. Larger studies are needed to test MUSA with other surgeons operating in other centers, the authors note.

“With respect to treatment of breast cancer–related lymphedema, we are continuing trials with more patients, more surgeons, and more centers,” Dr. Schols said in an interview.

“We expect that other centers – both national and international – are willing to test the MUSA,” he added.

Dr. Schols and several coauthors have disclosed no relevant financial relationships. Two coauthors are shareholders and hold positions at MicroSure.
 

This article first appeared on Medscape.com.

The first trial of robot-assisted, high-precision supermicrosurgery in humans has shown that the technique was safe for treating breast cancer–related lymphedema.

Although results were preliminary – only 20 patients participated, and a single highly skilled surgeon performed the supermicrosurgery – additional trials are underway to test the new robotic technique at other centers.

The pilot study was published online Feb. 11 in Nature Communications.

The new device, known as MUSA, was supplied by MicroSure.

MUSA allowed surgeons to connect tiny vessels, as small as 0.3-0.8 mm across, a technique referred to as supermicrosurgery. This technique can be used to connect blocked lymph vessels to veins, which can reestablish flow of lymphatic fluid and decrease arm swelling in women with breast cancer–related lymphedema, the researchers explain.

Only a few highly skilled surgeons worldwide can conduct supermicrosurgery using current surgical techniques, the authors comment.

“The success of supermicrosurgery is limited by the precision and stability of the surgeon’s hands. Robot-assisted supermicrosurgery has the potential to overcome this obstacle because more refined and subtle movements can be performed. Before now, no robots were able to perform this type of surgery,” coauthor Rutger M. Schols, MD, PhD, of Maastricht (the Netherlands) University Medical Center, said in an interview.

Robot-assisted surgery is not new – the Da Vinci system was the first robotic surgery device to be approved by the Food and Drug Administration. It was approved in 2000. However, Da Vinci was developed for minimally invasive surgery and is not precise enough for supermicrosurgery. And despite its $2 million price tag, Da Vinci has yet to show that it performs better than traditional surgery.

Designed specifically for supermicrosurgery

The MUSA robot was designed by surgeons at the Maastricht University Medical Center, engineers at the Eindhoven University of Technology, and the medical technology company Microsure specifically for reconstructive supermicrosurgery; all are located in the Netherlands. Two of the authors of the article hold positions and are shareholders in the company.

Surgeons activate MUSA using foot pedals and operate forceps-like joysticks to control high-precision surgical instruments that filter out hand tremors and scale down motions. For example, moving the joystick 1 cm causes the robot to move 0.10 mm. MUSA also works with standard microscopes found in most operating rooms.

To test MUSA, Dr. Schols and colleagues conducted a prospective, randomized trial that included 20 women with breast cancer–related lymphedema. The team randomly assigned eight women to undergo supermicrosurgery with MUSA and 12 women to undergo manual supermicrosurgery performed by a single surgeon. Two microsurgeons who were blinded to treatment groups evaluated the quality of the surgery using standardized scoring methods.

The results, which were adjusted for baseline factors, showed no significant differences in upper-limb lymphedema between the two groups 1 and 3 months after surgery, nor were there significant differences between the two groups in quality of life.

A slightly higher percentage of women in the MUSA group were able to discontinue daily use of a compressive garment to treat arm swelling at 3 months, compared with the group that underwent manual supermicrosurgery (87.5% vs. 83.3%). Participants reported no serious adverse events.

For the group that underwent manual surgery, the quality of anastomosis was significantly better, compared with the MUSA group. Surgical competency also was significantly higher in the group that underwent manual surgery.

The MUSA group experienced a longer total surgery time (mean, 115 min), compared with the group that underwent manual surgery (mean, 81 min). But the authors note that duration of surgery declined steeply over time for the MUSA group, suggesting a learning curve in using the robot.

The researchers caution that the study may have been too small to detect significant differences between groups. Larger studies are needed to test MUSA with other surgeons operating in other centers, the authors note.

“With respect to treatment of breast cancer–related lymphedema, we are continuing trials with more patients, more surgeons, and more centers,” Dr. Schols said in an interview.

“We expect that other centers – both national and international – are willing to test the MUSA,” he added.

Dr. Schols and several coauthors have disclosed no relevant financial relationships. Two coauthors are shareholders and hold positions at MicroSure.
 

This article first appeared on Medscape.com.

Adding pembrolizumab to neoadjuvant chemotherapy more than doubled the rate of pathologic complete response, compared with chemotherapy alone, in women with early-stage breast cancer enrolled in the phase 2 I-SPY2 trial.

Dr. Cecil Fox/National Cancer Institute

Pathologic complete response (pCR) rates up to 60% were reported for patients with high-risk, stage II/III breast cancer who received pembrolizumab plus chemotherapy in I-SPY2, an ongoing platform trial designed to rapidly screen multiple agents and pinpoint those with a high probability of success.

The doubling of pCR rates was seen in all three biomarker signatures studied, including ERBB2(HER2)-negative, hormone receptor (HR)-positive/ERBB2-negative, or triple-negative breast cancer.

These results mean that pembrolizumab can “graduate” from I-SPY2 and suggest a greater than 99% predictive probability that the pembrolizumab-plus-chemotherapy approach will be superior to chemotherapy alone in a phase 3 trial, according to Rita Nanda, MD, of the University of Chicago, and colleagues.

“Notably, pembrolizumab was the first agent of 10 studied to graduate in the HR-positive/ERBB2-negative signature since I-SPY2 opened in 2010,” Dr. Nanda and colleagues wrote in JAMA Oncology.

The I-SPY2 study has enrolled adult women with stage II/III breast cancer at high risk of recurrence. The control arm included 181 patients randomized to receive standard neoadjuvant paclitaxel followed by doxorubicin plus cyclophosphamide. The pembrolizumab arm included 69 patients who received the same chemotherapy regimen plus pembrolizumab given concurrently with paclitaxel.

In ERBB2-negative patients, the estimated pCR rates were 44% in the pembrolizumab arm and 17% in the control arm. In HR-positive/ERBB2-negative patients, the estimated pCR rates were 30% and 13%, respectively. In triple-negative patients, the estimated pCR rates were 60% and 22%, respectively.

Residual cancer burden classified as extensive was less often seen in the pembrolizumab-treated patients, the investigators noted.

Event-free survival was qualitatively similar between the pembrolizumab and control arms, although the investigators cautioned against drawing conclusions based on this exploratory analysis in a small number of patients.

“Patients who achieved pCR had excellent outcomes regardless of arm,” the investigators wrote.

Immune-related adverse events (irAEs) were seen in the pembrolizumab-treated patients, although most were grade 1 or 2 and managed with dose interruption or corticosteroid therapy.

The most common irAE was thyroid dysfunction in 13% of patients, which was on par with what was seen in previously published reports. By contrast, adrenal insufficiency was observed in about 9% of patients, which is higher than in published reports for reasons that are unclear.

“Future work to characterize the risk factors for developing irAEs is warranted to improve the therapeutic index of these agents,” Dr. Nanda and colleagues wrote.

Pembrolizumab plus standard neoadjuvant chemotherapy is being evaluated in two ongoing, randomized phase 3 trials – KEYNOTE 522, which is evaluating patients with triple-negative breast cancer, and KEYNOTE 756, which is focused on high-risk, HR-positive/ERBB2-negative breast cancer.

The ongoing I-SPY2 study is supported by a grant from the National Cancer Institute as well as funding from charitable organizations, pharmaceutical companies, and private individuals. The investigators disclosed relationships with a range of pharmaceutical companies.
 

SOURCE: Nanda R et al. JAMA Oncol. 2020 Feb 13. doi: 10.1001/jamaoncol.2019.6650.

Adding pembrolizumab to neoadjuvant chemotherapy more than doubled the rate of pathologic complete response, compared with chemotherapy alone, in women with early-stage breast cancer enrolled in the phase 2 I-SPY2 trial.

Dr. Cecil Fox/National Cancer Institute

Pathologic complete response (pCR) rates up to 60% were reported for patients with high-risk, stage II/III breast cancer who received pembrolizumab plus chemotherapy in I-SPY2, an ongoing platform trial designed to rapidly screen multiple agents and pinpoint those with a high probability of success.

The doubling of pCR rates was seen in all three biomarker signatures studied, including ERBB2(HER2)-negative, hormone receptor (HR)-positive/ERBB2-negative, or triple-negative breast cancer.

These results mean that pembrolizumab can “graduate” from I-SPY2 and suggest a greater than 99% predictive probability that the pembrolizumab-plus-chemotherapy approach will be superior to chemotherapy alone in a phase 3 trial, according to Rita Nanda, MD, of the University of Chicago, and colleagues.

“Notably, pembrolizumab was the first agent of 10 studied to graduate in the HR-positive/ERBB2-negative signature since I-SPY2 opened in 2010,” Dr. Nanda and colleagues wrote in JAMA Oncology.

The I-SPY2 study has enrolled adult women with stage II/III breast cancer at high risk of recurrence. The control arm included 181 patients randomized to receive standard neoadjuvant paclitaxel followed by doxorubicin plus cyclophosphamide. The pembrolizumab arm included 69 patients who received the same chemotherapy regimen plus pembrolizumab given concurrently with paclitaxel.

In ERBB2-negative patients, the estimated pCR rates were 44% in the pembrolizumab arm and 17% in the control arm. In HR-positive/ERBB2-negative patients, the estimated pCR rates were 30% and 13%, respectively. In triple-negative patients, the estimated pCR rates were 60% and 22%, respectively.

Residual cancer burden classified as extensive was less often seen in the pembrolizumab-treated patients, the investigators noted.

Event-free survival was qualitatively similar between the pembrolizumab and control arms, although the investigators cautioned against drawing conclusions based on this exploratory analysis in a small number of patients.

“Patients who achieved pCR had excellent outcomes regardless of arm,” the investigators wrote.

Immune-related adverse events (irAEs) were seen in the pembrolizumab-treated patients, although most were grade 1 or 2 and managed with dose interruption or corticosteroid therapy.

The most common irAE was thyroid dysfunction in 13% of patients, which was on par with what was seen in previously published reports. By contrast, adrenal insufficiency was observed in about 9% of patients, which is higher than in published reports for reasons that are unclear.

“Future work to characterize the risk factors for developing irAEs is warranted to improve the therapeutic index of these agents,” Dr. Nanda and colleagues wrote.

Pembrolizumab plus standard neoadjuvant chemotherapy is being evaluated in two ongoing, randomized phase 3 trials – KEYNOTE 522, which is evaluating patients with triple-negative breast cancer, and KEYNOTE 756, which is focused on high-risk, HR-positive/ERBB2-negative breast cancer.

The ongoing I-SPY2 study is supported by a grant from the National Cancer Institute as well as funding from charitable organizations, pharmaceutical companies, and private individuals. The investigators disclosed relationships with a range of pharmaceutical companies.
 

SOURCE: Nanda R et al. JAMA Oncol. 2020 Feb 13. doi: 10.1001/jamaoncol.2019.6650.

Adding pembrolizumab to neoadjuvant chemotherapy more than doubled the rate of pathologic complete response, compared with chemotherapy alone, in women with early-stage breast cancer enrolled in the phase 2 I-SPY2 trial.

Dr. Cecil Fox/National Cancer Institute

Pathologic complete response (pCR) rates up to 60% were reported for patients with high-risk, stage II/III breast cancer who received pembrolizumab plus chemotherapy in I-SPY2, an ongoing platform trial designed to rapidly screen multiple agents and pinpoint those with a high probability of success.

The doubling of pCR rates was seen in all three biomarker signatures studied, including ERBB2(HER2)-negative, hormone receptor (HR)-positive/ERBB2-negative, or triple-negative breast cancer.

These results mean that pembrolizumab can “graduate” from I-SPY2 and suggest a greater than 99% predictive probability that the pembrolizumab-plus-chemotherapy approach will be superior to chemotherapy alone in a phase 3 trial, according to Rita Nanda, MD, of the University of Chicago, and colleagues.

“Notably, pembrolizumab was the first agent of 10 studied to graduate in the HR-positive/ERBB2-negative signature since I-SPY2 opened in 2010,” Dr. Nanda and colleagues wrote in JAMA Oncology.

The I-SPY2 study has enrolled adult women with stage II/III breast cancer at high risk of recurrence. The control arm included 181 patients randomized to receive standard neoadjuvant paclitaxel followed by doxorubicin plus cyclophosphamide. The pembrolizumab arm included 69 patients who received the same chemotherapy regimen plus pembrolizumab given concurrently with paclitaxel.

In ERBB2-negative patients, the estimated pCR rates were 44% in the pembrolizumab arm and 17% in the control arm. In HR-positive/ERBB2-negative patients, the estimated pCR rates were 30% and 13%, respectively. In triple-negative patients, the estimated pCR rates were 60% and 22%, respectively.

Residual cancer burden classified as extensive was less often seen in the pembrolizumab-treated patients, the investigators noted.

Event-free survival was qualitatively similar between the pembrolizumab and control arms, although the investigators cautioned against drawing conclusions based on this exploratory analysis in a small number of patients.

“Patients who achieved pCR had excellent outcomes regardless of arm,” the investigators wrote.

Immune-related adverse events (irAEs) were seen in the pembrolizumab-treated patients, although most were grade 1 or 2 and managed with dose interruption or corticosteroid therapy.

The most common irAE was thyroid dysfunction in 13% of patients, which was on par with what was seen in previously published reports. By contrast, adrenal insufficiency was observed in about 9% of patients, which is higher than in published reports for reasons that are unclear.

“Future work to characterize the risk factors for developing irAEs is warranted to improve the therapeutic index of these agents,” Dr. Nanda and colleagues wrote.

Pembrolizumab plus standard neoadjuvant chemotherapy is being evaluated in two ongoing, randomized phase 3 trials – KEYNOTE 522, which is evaluating patients with triple-negative breast cancer, and KEYNOTE 756, which is focused on high-risk, HR-positive/ERBB2-negative breast cancer.

The ongoing I-SPY2 study is supported by a grant from the National Cancer Institute as well as funding from charitable organizations, pharmaceutical companies, and private individuals. The investigators disclosed relationships with a range of pharmaceutical companies.
 

SOURCE: Nanda R et al. JAMA Oncol. 2020 Feb 13. doi: 10.1001/jamaoncol.2019.6650.

Clinical trials supporting Food and Drug Adminstration approval of contemporary cancer therapies frequently failed to capture major adverse cardiovascular events (MACE) and, when they did, reported rates 2.6-fold lower than noncancer trials, new research shows.

Overall, 51.3% of trials did not report MACE, with that number reaching 57.6% in trials enrolling patients with baseline cardiovascular disease (CVD).

Nearly 40% of trials did not report any CVD events in follow-up, the authors reported online Feb. 10, 2020, in the Journal of the American College of Cardiology (2020;75:620-8).

“Even in drug classes where there were established or emerging associations with cardiotoxic events, often there were no reported heart events or cardiovascular events across years of follow-up in trials that examined hundreds or even thousands of patients. That was actually pretty surprising,” senior author Daniel Addison, MD, codirector of the cardio-oncology program at the Ohio State University Medical Center, Columbus, said in an interview.

The study was prompted by a series of events that crescendoed when his team was called to the ICU to determine whether a novel targeted agent played a role in the heart decline of a patient with acute myeloid leukemia. “I had a resident ask me a very important question: ‘How do we really know for sure that the trial actually reflects the true risk of heart events?’ to which I told him, ‘it’s difficult to know,’ ” he said.

“I think many of us rely heavily on what we see in the trials, particularly when they make it to the top journals, and quite frankly, we generally take it at face value,” Dr. Addison observed.
 

Lower Rate of Reported Events

The investigators reviewed CV events reported in 97,365 patients (median age, 61 years; 46% female) enrolled in 189 phase 2 and 3 trials supporting FDA approval of 123 anticancer drugs from 1998 to 2018. Biologic, targeted, or immune-based therapies accounted for 72.5% of drug approvals.

Over 148,138 person-years of follow-up (median trial duration, 30 months), there were 1,148 incidents of MACE (375 heart failure, 253 MIs, 180 strokes, 65 atrial fibrillation, 29 coronary revascularizations, and 246 CVD deaths). MACE rates were higher in the intervention group than in the control group (792 vs. 356; P less than .01). Among the 64 trials that excluded patients with baseline CVD, there were 269 incidents of MACE.

To put this finding in context, the researchers examined the reported incidence of MACE among some 6,000 similarly aged participants in the Multi-Ethnic Study of Atherosclerosis (MESA). The overall weighted-average incidence rate was 1,408 per 100,000 person-years among MESA participants, compared with 542 events per 100,000 person-years among oncology trial participants (716 per 100,000 in the intervention arm). This represents a reported-to-expected ratio of 0.38 – a 2.6-fold lower rate of reported events (P less than .001) – and a risk difference of 866.

Further, MACE reporting was lower by a factor of 1.7 among all cancer trial participants irrespective of baseline CVD status (reported-to-expected ratio, 0.56; risk difference, 613; P less than .001).

There was no significant difference in MACE reporting between independent or industry-sponsored trials, the authors report.
 

No malicious intent

“There are likely some that might lean toward not wanting to attribute blame to a new drug when the drug is in a study, but I really think that the leading factor is lack of awareness,” Dr. Addison said. “I’ve talked with several cancer collaborators around the country who run large clinical trials, and I think often, when an event may be brought to someone’s attention, there is a tendency to just write it off as kind of a generic expected event due to age, or just something that’s not really pertinent to the study. So they don’t really focus on it as much.”

“Closer collaboration between cardiologists and cancer physicians is needed to better determine true cardiac risks among patients treated with these drugs.”

Breast cancer oncologist Marc E. Lippman, MD, of Georgetown University Medical Center and Georgetown Lombardi Comprehensive Cancer Center, Washington, D.C., isn’t convinced a lack of awareness is the culprit.

“I don’t agree with that at all,” he said in an interview. “I think there are very, very clear rules and guidelines these days for adverse-event reporting. I think that’s not a very likely explanation – that it’s not on the radar.”

Part of the problem may be that some of the toxicities, particularly cardiovascular, may not emerge for years, he said. Participant screening for the trials also likely removed patients with high cardiovascular risk. “It’s very understandable to me – I’m not saying it’s good particularly – but I think it’s very understandable that, if you’re trying to develop a drug, the last thing you’d want to have is a lot of toxicity that you might have avoided by just being restrictive in who you let into the study,” Dr. Lippman said.

The underreported CVD events may also reflect the rapidly changing profile of cardiovascular toxicities associated with novel anticancer therapies.

“Providers, both cancer and noncancer, generally put cardiotoxicity in the box of anthracyclines and radiation, but particularly over the last decade, we’ve begun to understand it’s well beyond any one class of drugs,” Dr. Addison said.

“I agree completely,” Dr. Lippman said. For example, “the checkpoint inhibitors are so unbelievably different in terms of their toxicities that many people simply didn’t even know what they were getting into at first.”
 

One size does not fit all

Javid Moslehi, MD, director of the cardio-oncology program at Vanderbilt University, Nashville, Tenn., said echocardiography – recommended to detect changes in left ventricular function in patients exposed to anthracyclines or targeted agents like trastuzumab (Herceptin) – isn’t enough to address today’s cancer therapy–related CVD events.

Courtesy Joe Howell

“Initial drugs like anthracyclines or Herceptin in cardio-oncology were associated with systolic cardiac dysfunction, whereas the majority of issues we see in the cardio-oncology clinics today are vascular, metabolic, arrhythmogenic, and inflammatory,” he said in an interview. “Echocardiography misses the big and increasingly complex picture.”

His group, for example, has been studying myocarditis associated with immunotherapies, but none of the clinical trials require screening or surveillance for myocarditis with a cardiac biomarker like troponin.

The group also recently identified 303 deaths in patients exposed to ibrutinib, a drug that revolutionized the treatment of several B-cell malignancies but is associated with higher rates of atrial fibrillation, which is also associated with increased bleeding risk. “So there’s a little bit of a double whammy there, given that we often treat atrial fibrillation with anticoagulation and where we can cause complications in patients,” Dr. Moslehi noted.

Although there needs to be closer collaboration between cardiologists and oncologists on individual trials, cardiologists also have to realize that oncology care has become very personalized, he suggested.

“What’s probably relevant for the breast cancer patient may not be relevant for the prostate cancer patient and their respective treatments,” Dr. Moslehi said. “So if we were to say, ‘every person should get an echo,’ that may be less relevant to the prostate cancer patient where treatments can cause vascular and metabolic perturbations or to the patient treated with immunotherapy who may have myocarditis, where many of the echos can be normal. There’s no one-size-fits-all for these things.”

Wearable technologies like smartwatches could play a role in improving the reporting of CVD events with novel therapies but a lot more research needs to be done to validate these tools, Dr. Addison said. “But as we continue on into the 21st century, this is going to expand and may potentially help us,” he added.

In the interim, better standardization is needed of the cardiovascular events reported in oncology trials, particularly the Common Terminology Criteria for Adverse Events (CTCAE), said Dr. Moslehi, who also serves as chair of the American Heart Association’s subcommittee on cardio-oncology.

“Cardiovascular definitions are not exactly uniform and are not consistent with what we in cardiology consider to be important or relevant,” he said. “So I think there needs to be better standardization of these definitions, specifically within the CTCAE, which is what the oncologists use to identify adverse events.”

In a linked editorial (J Am Coll Cardiol. 2020;75:629-31), Dr. Lippman and cardiologist Nanette Bishopric, MD, of the Medstar Heart and Vascular Institute in Washington, D.C., suggested it may also be time to organize a consortium that can carry out “rigorous multicenter clinical investigations to evaluate the cardiotoxicity of emerging cancer treatments,” similar to the Thrombosis in Myocardial Infarction Study Group.

“The success of this consortium in pioneering and targeting multiple generations of drugs for the treatment of MI, involving tens of thousands of patients and thousands of collaborations across multiple national borders, is a model for how to move forward in providing the new hope of cancer cure without the trade-off of years lost to heart disease,” the editorialists concluded.

The study was supported in part by National Institutes of Health grants, including a K12-CA133250 grant to Dr. Addison. Dr. Bishopric reported being on the scientific board of C&C Biopharma. Dr. Lippman reports being on the board of directors of and holding stock in Seattle Genetics. Dr. Moslehi reported having served on advisory boards for Pfizer, Novartis, Bristol-Myers Squibb, Deciphera, Audentes Pharmaceuticals, Nektar, Takeda, Ipsen, Myokardia, AstraZeneca, GlaxoSmithKline, Intrexon, and Regeneron.

This article first appeared on Medscape.com.

Clinical trials supporting Food and Drug Adminstration approval of contemporary cancer therapies frequently failed to capture major adverse cardiovascular events (MACE) and, when they did, reported rates 2.6-fold lower than noncancer trials, new research shows.

Overall, 51.3% of trials did not report MACE, with that number reaching 57.6% in trials enrolling patients with baseline cardiovascular disease (CVD).

Nearly 40% of trials did not report any CVD events in follow-up, the authors reported online Feb. 10, 2020, in the Journal of the American College of Cardiology (2020;75:620-8).

“Even in drug classes where there were established or emerging associations with cardiotoxic events, often there were no reported heart events or cardiovascular events across years of follow-up in trials that examined hundreds or even thousands of patients. That was actually pretty surprising,” senior author Daniel Addison, MD, codirector of the cardio-oncology program at the Ohio State University Medical Center, Columbus, said in an interview.

The study was prompted by a series of events that crescendoed when his team was called to the ICU to determine whether a novel targeted agent played a role in the heart decline of a patient with acute myeloid leukemia. “I had a resident ask me a very important question: ‘How do we really know for sure that the trial actually reflects the true risk of heart events?’ to which I told him, ‘it’s difficult to know,’ ” he said.

“I think many of us rely heavily on what we see in the trials, particularly when they make it to the top journals, and quite frankly, we generally take it at face value,” Dr. Addison observed.
 

Lower Rate of Reported Events

The investigators reviewed CV events reported in 97,365 patients (median age, 61 years; 46% female) enrolled in 189 phase 2 and 3 trials supporting FDA approval of 123 anticancer drugs from 1998 to 2018. Biologic, targeted, or immune-based therapies accounted for 72.5% of drug approvals.

Over 148,138 person-years of follow-up (median trial duration, 30 months), there were 1,148 incidents of MACE (375 heart failure, 253 MIs, 180 strokes, 65 atrial fibrillation, 29 coronary revascularizations, and 246 CVD deaths). MACE rates were higher in the intervention group than in the control group (792 vs. 356; P less than .01). Among the 64 trials that excluded patients with baseline CVD, there were 269 incidents of MACE.

To put this finding in context, the researchers examined the reported incidence of MACE among some 6,000 similarly aged participants in the Multi-Ethnic Study of Atherosclerosis (MESA). The overall weighted-average incidence rate was 1,408 per 100,000 person-years among MESA participants, compared with 542 events per 100,000 person-years among oncology trial participants (716 per 100,000 in the intervention arm). This represents a reported-to-expected ratio of 0.38 – a 2.6-fold lower rate of reported events (P less than .001) – and a risk difference of 866.

Further, MACE reporting was lower by a factor of 1.7 among all cancer trial participants irrespective of baseline CVD status (reported-to-expected ratio, 0.56; risk difference, 613; P less than .001).

There was no significant difference in MACE reporting between independent or industry-sponsored trials, the authors report.
 

No malicious intent

“There are likely some that might lean toward not wanting to attribute blame to a new drug when the drug is in a study, but I really think that the leading factor is lack of awareness,” Dr. Addison said. “I’ve talked with several cancer collaborators around the country who run large clinical trials, and I think often, when an event may be brought to someone’s attention, there is a tendency to just write it off as kind of a generic expected event due to age, or just something that’s not really pertinent to the study. So they don’t really focus on it as much.”

“Closer collaboration between cardiologists and cancer physicians is needed to better determine true cardiac risks among patients treated with these drugs.”

Breast cancer oncologist Marc E. Lippman, MD, of Georgetown University Medical Center and Georgetown Lombardi Comprehensive Cancer Center, Washington, D.C., isn’t convinced a lack of awareness is the culprit.

“I don’t agree with that at all,” he said in an interview. “I think there are very, very clear rules and guidelines these days for adverse-event reporting. I think that’s not a very likely explanation – that it’s not on the radar.”

Part of the problem may be that some of the toxicities, particularly cardiovascular, may not emerge for years, he said. Participant screening for the trials also likely removed patients with high cardiovascular risk. “It’s very understandable to me – I’m not saying it’s good particularly – but I think it’s very understandable that, if you’re trying to develop a drug, the last thing you’d want to have is a lot of toxicity that you might have avoided by just being restrictive in who you let into the study,” Dr. Lippman said.

The underreported CVD events may also reflect the rapidly changing profile of cardiovascular toxicities associated with novel anticancer therapies.

“Providers, both cancer and noncancer, generally put cardiotoxicity in the box of anthracyclines and radiation, but particularly over the last decade, we’ve begun to understand it’s well beyond any one class of drugs,” Dr. Addison said.

“I agree completely,” Dr. Lippman said. For example, “the checkpoint inhibitors are so unbelievably different in terms of their toxicities that many people simply didn’t even know what they were getting into at first.”
 

One size does not fit all

Javid Moslehi, MD, director of the cardio-oncology program at Vanderbilt University, Nashville, Tenn., said echocardiography – recommended to detect changes in left ventricular function in patients exposed to anthracyclines or targeted agents like trastuzumab (Herceptin) – isn’t enough to address today’s cancer therapy–related CVD events.

Courtesy Joe Howell

“Initial drugs like anthracyclines or Herceptin in cardio-oncology were associated with systolic cardiac dysfunction, whereas the majority of issues we see in the cardio-oncology clinics today are vascular, metabolic, arrhythmogenic, and inflammatory,” he said in an interview. “Echocardiography misses the big and increasingly complex picture.”

His group, for example, has been studying myocarditis associated with immunotherapies, but none of the clinical trials require screening or surveillance for myocarditis with a cardiac biomarker like troponin.

The group also recently identified 303 deaths in patients exposed to ibrutinib, a drug that revolutionized the treatment of several B-cell malignancies but is associated with higher rates of atrial fibrillation, which is also associated with increased bleeding risk. “So there’s a little bit of a double whammy there, given that we often treat atrial fibrillation with anticoagulation and where we can cause complications in patients,” Dr. Moslehi noted.

Although there needs to be closer collaboration between cardiologists and oncologists on individual trials, cardiologists also have to realize that oncology care has become very personalized, he suggested.

“What’s probably relevant for the breast cancer patient may not be relevant for the prostate cancer patient and their respective treatments,” Dr. Moslehi said. “So if we were to say, ‘every person should get an echo,’ that may be less relevant to the prostate cancer patient where treatments can cause vascular and metabolic perturbations or to the patient treated with immunotherapy who may have myocarditis, where many of the echos can be normal. There’s no one-size-fits-all for these things.”

Wearable technologies like smartwatches could play a role in improving the reporting of CVD events with novel therapies but a lot more research needs to be done to validate these tools, Dr. Addison said. “But as we continue on into the 21st century, this is going to expand and may potentially help us,” he added.

In the interim, better standardization is needed of the cardiovascular events reported in oncology trials, particularly the Common Terminology Criteria for Adverse Events (CTCAE), said Dr. Moslehi, who also serves as chair of the American Heart Association’s subcommittee on cardio-oncology.

“Cardiovascular definitions are not exactly uniform and are not consistent with what we in cardiology consider to be important or relevant,” he said. “So I think there needs to be better standardization of these definitions, specifically within the CTCAE, which is what the oncologists use to identify adverse events.”

In a linked editorial (J Am Coll Cardiol. 2020;75:629-31), Dr. Lippman and cardiologist Nanette Bishopric, MD, of the Medstar Heart and Vascular Institute in Washington, D.C., suggested it may also be time to organize a consortium that can carry out “rigorous multicenter clinical investigations to evaluate the cardiotoxicity of emerging cancer treatments,” similar to the Thrombosis in Myocardial Infarction Study Group.

“The success of this consortium in pioneering and targeting multiple generations of drugs for the treatment of MI, involving tens of thousands of patients and thousands of collaborations across multiple national borders, is a model for how to move forward in providing the new hope of cancer cure without the trade-off of years lost to heart disease,” the editorialists concluded.

The study was supported in part by National Institutes of Health grants, including a K12-CA133250 grant to Dr. Addison. Dr. Bishopric reported being on the scientific board of C&C Biopharma. Dr. Lippman reports being on the board of directors of and holding stock in Seattle Genetics. Dr. Moslehi reported having served on advisory boards for Pfizer, Novartis, Bristol-Myers Squibb, Deciphera, Audentes Pharmaceuticals, Nektar, Takeda, Ipsen, Myokardia, AstraZeneca, GlaxoSmithKline, Intrexon, and Regeneron.

This article first appeared on Medscape.com.

Clinical trials supporting Food and Drug Adminstration approval of contemporary cancer therapies frequently failed to capture major adverse cardiovascular events (MACE) and, when they did, reported rates 2.6-fold lower than noncancer trials, new research shows.

Overall, 51.3% of trials did not report MACE, with that number reaching 57.6% in trials enrolling patients with baseline cardiovascular disease (CVD).

Nearly 40% of trials did not report any CVD events in follow-up, the authors reported online Feb. 10, 2020, in the Journal of the American College of Cardiology (2020;75:620-8).

“Even in drug classes where there were established or emerging associations with cardiotoxic events, often there were no reported heart events or cardiovascular events across years of follow-up in trials that examined hundreds or even thousands of patients. That was actually pretty surprising,” senior author Daniel Addison, MD, codirector of the cardio-oncology program at the Ohio State University Medical Center, Columbus, said in an interview.

The study was prompted by a series of events that crescendoed when his team was called to the ICU to determine whether a novel targeted agent played a role in the heart decline of a patient with acute myeloid leukemia. “I had a resident ask me a very important question: ‘How do we really know for sure that the trial actually reflects the true risk of heart events?’ to which I told him, ‘it’s difficult to know,’ ” he said.

“I think many of us rely heavily on what we see in the trials, particularly when they make it to the top journals, and quite frankly, we generally take it at face value,” Dr. Addison observed.
 

Lower Rate of Reported Events

The investigators reviewed CV events reported in 97,365 patients (median age, 61 years; 46% female) enrolled in 189 phase 2 and 3 trials supporting FDA approval of 123 anticancer drugs from 1998 to 2018. Biologic, targeted, or immune-based therapies accounted for 72.5% of drug approvals.

Over 148,138 person-years of follow-up (median trial duration, 30 months), there were 1,148 incidents of MACE (375 heart failure, 253 MIs, 180 strokes, 65 atrial fibrillation, 29 coronary revascularizations, and 246 CVD deaths). MACE rates were higher in the intervention group than in the control group (792 vs. 356; P less than .01). Among the 64 trials that excluded patients with baseline CVD, there were 269 incidents of MACE.

To put this finding in context, the researchers examined the reported incidence of MACE among some 6,000 similarly aged participants in the Multi-Ethnic Study of Atherosclerosis (MESA). The overall weighted-average incidence rate was 1,408 per 100,000 person-years among MESA participants, compared with 542 events per 100,000 person-years among oncology trial participants (716 per 100,000 in the intervention arm). This represents a reported-to-expected ratio of 0.38 – a 2.6-fold lower rate of reported events (P less than .001) – and a risk difference of 866.

Further, MACE reporting was lower by a factor of 1.7 among all cancer trial participants irrespective of baseline CVD status (reported-to-expected ratio, 0.56; risk difference, 613; P less than .001).

There was no significant difference in MACE reporting between independent or industry-sponsored trials, the authors report.
 

No malicious intent

“There are likely some that might lean toward not wanting to attribute blame to a new drug when the drug is in a study, but I really think that the leading factor is lack of awareness,” Dr. Addison said. “I’ve talked with several cancer collaborators around the country who run large clinical trials, and I think often, when an event may be brought to someone’s attention, there is a tendency to just write it off as kind of a generic expected event due to age, or just something that’s not really pertinent to the study. So they don’t really focus on it as much.”

“Closer collaboration between cardiologists and cancer physicians is needed to better determine true cardiac risks among patients treated with these drugs.”

Breast cancer oncologist Marc E. Lippman, MD, of Georgetown University Medical Center and Georgetown Lombardi Comprehensive Cancer Center, Washington, D.C., isn’t convinced a lack of awareness is the culprit.

“I don’t agree with that at all,” he said in an interview. “I think there are very, very clear rules and guidelines these days for adverse-event reporting. I think that’s not a very likely explanation – that it’s not on the radar.”

Part of the problem may be that some of the toxicities, particularly cardiovascular, may not emerge for years, he said. Participant screening for the trials also likely removed patients with high cardiovascular risk. “It’s very understandable to me – I’m not saying it’s good particularly – but I think it’s very understandable that, if you’re trying to develop a drug, the last thing you’d want to have is a lot of toxicity that you might have avoided by just being restrictive in who you let into the study,” Dr. Lippman said.

The underreported CVD events may also reflect the rapidly changing profile of cardiovascular toxicities associated with novel anticancer therapies.

“Providers, both cancer and noncancer, generally put cardiotoxicity in the box of anthracyclines and radiation, but particularly over the last decade, we’ve begun to understand it’s well beyond any one class of drugs,” Dr. Addison said.

“I agree completely,” Dr. Lippman said. For example, “the checkpoint inhibitors are so unbelievably different in terms of their toxicities that many people simply didn’t even know what they were getting into at first.”
 

One size does not fit all

Javid Moslehi, MD, director of the cardio-oncology program at Vanderbilt University, Nashville, Tenn., said echocardiography – recommended to detect changes in left ventricular function in patients exposed to anthracyclines or targeted agents like trastuzumab (Herceptin) – isn’t enough to address today’s cancer therapy–related CVD events.

Courtesy Joe Howell

“Initial drugs like anthracyclines or Herceptin in cardio-oncology were associated with systolic cardiac dysfunction, whereas the majority of issues we see in the cardio-oncology clinics today are vascular, metabolic, arrhythmogenic, and inflammatory,” he said in an interview. “Echocardiography misses the big and increasingly complex picture.”

His group, for example, has been studying myocarditis associated with immunotherapies, but none of the clinical trials require screening or surveillance for myocarditis with a cardiac biomarker like troponin.

The group also recently identified 303 deaths in patients exposed to ibrutinib, a drug that revolutionized the treatment of several B-cell malignancies but is associated with higher rates of atrial fibrillation, which is also associated with increased bleeding risk. “So there’s a little bit of a double whammy there, given that we often treat atrial fibrillation with anticoagulation and where we can cause complications in patients,” Dr. Moslehi noted.

Although there needs to be closer collaboration between cardiologists and oncologists on individual trials, cardiologists also have to realize that oncology care has become very personalized, he suggested.

“What’s probably relevant for the breast cancer patient may not be relevant for the prostate cancer patient and their respective treatments,” Dr. Moslehi said. “So if we were to say, ‘every person should get an echo,’ that may be less relevant to the prostate cancer patient where treatments can cause vascular and metabolic perturbations or to the patient treated with immunotherapy who may have myocarditis, where many of the echos can be normal. There’s no one-size-fits-all for these things.”

Wearable technologies like smartwatches could play a role in improving the reporting of CVD events with novel therapies but a lot more research needs to be done to validate these tools, Dr. Addison said. “But as we continue on into the 21st century, this is going to expand and may potentially help us,” he added.

In the interim, better standardization is needed of the cardiovascular events reported in oncology trials, particularly the Common Terminology Criteria for Adverse Events (CTCAE), said Dr. Moslehi, who also serves as chair of the American Heart Association’s subcommittee on cardio-oncology.

“Cardiovascular definitions are not exactly uniform and are not consistent with what we in cardiology consider to be important or relevant,” he said. “So I think there needs to be better standardization of these definitions, specifically within the CTCAE, which is what the oncologists use to identify adverse events.”

In a linked editorial (J Am Coll Cardiol. 2020;75:629-31), Dr. Lippman and cardiologist Nanette Bishopric, MD, of the Medstar Heart and Vascular Institute in Washington, D.C., suggested it may also be time to organize a consortium that can carry out “rigorous multicenter clinical investigations to evaluate the cardiotoxicity of emerging cancer treatments,” similar to the Thrombosis in Myocardial Infarction Study Group.

“The success of this consortium in pioneering and targeting multiple generations of drugs for the treatment of MI, involving tens of thousands of patients and thousands of collaborations across multiple national borders, is a model for how to move forward in providing the new hope of cancer cure without the trade-off of years lost to heart disease,” the editorialists concluded.

The study was supported in part by National Institutes of Health grants, including a K12-CA133250 grant to Dr. Addison. Dr. Bishopric reported being on the scientific board of C&C Biopharma. Dr. Lippman reports being on the board of directors of and holding stock in Seattle Genetics. Dr. Moslehi reported having served on advisory boards for Pfizer, Novartis, Bristol-Myers Squibb, Deciphera, Audentes Pharmaceuticals, Nektar, Takeda, Ipsen, Myokardia, AstraZeneca, GlaxoSmithKline, Intrexon, and Regeneron.

This article first appeared on Medscape.com.