Breast Cancer

Of the approximately 1 million benign breast biopsies obtained annually from US women, some 10% yield a diagnosis of atypical hyperplasia, microscopically classified as ductal or lobular. Atypical hyperplasia represents a “proliferation of dysplastic, mono­tonous epithelial-cell populations that include clonal subpopulations. In models of breast carcinogenesis, atypical hyperplasia occupies a transitional zone between benign and malignant disease,” write Hartmann and colleagues, the authors of a recent special report in the New England Journal of Medicine.¹

Long-term follow-up studies have found atypical hyperplasia to confer a relative risk for breast cancer of 4.0. Although these findings are well established, the cumulative absolute risk for breast cancer conferred by a diagnosis of atypical hyperplasia only recently has been described. Hartmann and colleagues note that it approaches 30% over 25 years.¹

Recommendations for clinical practice
The authors of this special report do a service to women and their clinicians by pointing out the high long-term risk of malignancy faced by women with atypical hyperplasia of the breast. They also make a number of important recommendations for practice:

Most women will not develop breast malignancy
As Hartmann and colleagues point out, all is not dire once a woman is diagnosed with atypical hyperplasia of the breast. In most of these women, breast cancer will not develop—and if it does develop, it may occur at an age when mortality from other causes is more likely than from breast cancer. In this respect, women with atypical hyperplasia of the breast are different from carriers of BRCA mutations. Although women with atypical hyperplasia as well as mutation carriers are both at high lifetime risk for breast cancer, breast malignancies occur at an earlier age in mutation carriers. Accordingly, as the authors of this special report advise, in general, a diagnosis of atypical hyperplasia should not be considered an indication for risk-reducing bilateral mastectomy.

Share your thoughts on this article! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

Of the approximately 1 million benign breast biopsies obtained annually from US women, some 10% yield a diagnosis of atypical hyperplasia, microscopically classified as ductal or lobular. Atypical hyperplasia represents a “proliferation of dysplastic, mono­tonous epithelial-cell populations that include clonal subpopulations. In models of breast carcinogenesis, atypical hyperplasia occupies a transitional zone between benign and malignant disease,” write Hartmann and colleagues, the authors of a recent special report in the New England Journal of Medicine.¹

Long-term follow-up studies have found atypical hyperplasia to confer a relative risk for breast cancer of 4.0. Although these findings are well established, the cumulative absolute risk for breast cancer conferred by a diagnosis of atypical hyperplasia only recently has been described. Hartmann and colleagues note that it approaches 30% over 25 years.¹

Recommendations for clinical practice
The authors of this special report do a service to women and their clinicians by pointing out the high long-term risk of malignancy faced by women with atypical hyperplasia of the breast. They also make a number of important recommendations for practice:

Most women will not develop breast malignancy
As Hartmann and colleagues point out, all is not dire once a woman is diagnosed with atypical hyperplasia of the breast. In most of these women, breast cancer will not develop—and if it does develop, it may occur at an age when mortality from other causes is more likely than from breast cancer. In this respect, women with atypical hyperplasia of the breast are different from carriers of BRCA mutations. Although women with atypical hyperplasia as well as mutation carriers are both at high lifetime risk for breast cancer, breast malignancies occur at an earlier age in mutation carriers. Accordingly, as the authors of this special report advise, in general, a diagnosis of atypical hyperplasia should not be considered an indication for risk-reducing bilateral mastectomy.

Share your thoughts on this article! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

Of the approximately 1 million benign breast biopsies obtained annually from US women, some 10% yield a diagnosis of atypical hyperplasia, microscopically classified as ductal or lobular. Atypical hyperplasia represents a “proliferation of dysplastic, mono­tonous epithelial-cell populations that include clonal subpopulations. In models of breast carcinogenesis, atypical hyperplasia occupies a transitional zone between benign and malignant disease,” write Hartmann and colleagues, the authors of a recent special report in the New England Journal of Medicine.¹

Long-term follow-up studies have found atypical hyperplasia to confer a relative risk for breast cancer of 4.0. Although these findings are well established, the cumulative absolute risk for breast cancer conferred by a diagnosis of atypical hyperplasia only recently has been described. Hartmann and colleagues note that it approaches 30% over 25 years.¹

Recommendations for clinical practice
The authors of this special report do a service to women and their clinicians by pointing out the high long-term risk of malignancy faced by women with atypical hyperplasia of the breast. They also make a number of important recommendations for practice:

Most women will not develop breast malignancy
As Hartmann and colleagues point out, all is not dire once a woman is diagnosed with atypical hyperplasia of the breast. In most of these women, breast cancer will not develop—and if it does develop, it may occur at an age when mortality from other causes is more likely than from breast cancer. In this respect, women with atypical hyperplasia of the breast are different from carriers of BRCA mutations. Although women with atypical hyperplasia as well as mutation carriers are both at high lifetime risk for breast cancer, breast malignancies occur at an earlier age in mutation carriers. Accordingly, as the authors of this special report advise, in general, a diagnosis of atypical hyperplasia should not be considered an indication for risk-reducing bilateral mastectomy.

Share your thoughts on this article! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

The rates of breast-conserving surgery have increased over the last 2 decades among women with early-stage breast cancers in the United States, but disparities persist, based on an analysis of data from the National Cancer Data Base.

The rate of breast-conserving surgery has risen from approximately 54% in 1998 to 60% in 2011, but this rate may have been affected by “technical advances and changes in societal norms [that] include genetic testing for BRCA1 and BRCA2 mutation, advances in reconstruction techniques, breast magnetic resonance imaging, and increased patient interest in contralateral prophylactic mastectomy,” Dr. Meeghan Lautner and her colleagues at University of Texas MD Anderson Cancer Care Center, Houston, wrote.

“Among the most encouraging findings from our analysis is the considerable improvement of disparities based on facility type and the options afforded to older populations … however, insurance, income, and travel distance to treatment facilities persist as key barriers to [breast-conserving therapy] use,” the researchers said.

Their analysis of a cohort of 727,927 women, published online June 17 in JAMA Surgery, showed that women with early breast cancer were less likely to receive breast-conserving surgery if they had a low educational level, public or no health insurance, and low income.

Women aged 52-61 years were 14% more likely to be treated with breast-conserving surgery, compared with younger women. White race, fewer comorbidities, and living closer to a treatment facility were all positively associated with being treated with breast-conserving surgery.

Those in southern regions of the United States were significantly less likely to receive breast-conserving surgery, compared with those in the Northeast. The researchers said their data suggest the lower rates are because of the greater travel distances to treatment facilities in the South.

Women with no insurance were 25% less likely than those with private insurance to have breast-conserving therapy (JAMA Surgery 2015 June 17 [doi:10.1001/jamasurg.2015.1102]).

The researchers declared no conflicts of interest.

The rates of breast-conserving surgery have increased over the last 2 decades among women with early-stage breast cancers in the United States, but disparities persist, based on an analysis of data from the National Cancer Data Base.

The rate of breast-conserving surgery has risen from approximately 54% in 1998 to 60% in 2011, but this rate may have been affected by “technical advances and changes in societal norms [that] include genetic testing for BRCA1 and BRCA2 mutation, advances in reconstruction techniques, breast magnetic resonance imaging, and increased patient interest in contralateral prophylactic mastectomy,” Dr. Meeghan Lautner and her colleagues at University of Texas MD Anderson Cancer Care Center, Houston, wrote.

“Among the most encouraging findings from our analysis is the considerable improvement of disparities based on facility type and the options afforded to older populations … however, insurance, income, and travel distance to treatment facilities persist as key barriers to [breast-conserving therapy] use,” the researchers said.

Their analysis of a cohort of 727,927 women, published online June 17 in JAMA Surgery, showed that women with early breast cancer were less likely to receive breast-conserving surgery if they had a low educational level, public or no health insurance, and low income.

Women aged 52-61 years were 14% more likely to be treated with breast-conserving surgery, compared with younger women. White race, fewer comorbidities, and living closer to a treatment facility were all positively associated with being treated with breast-conserving surgery.

Those in southern regions of the United States were significantly less likely to receive breast-conserving surgery, compared with those in the Northeast. The researchers said their data suggest the lower rates are because of the greater travel distances to treatment facilities in the South.

Women with no insurance were 25% less likely than those with private insurance to have breast-conserving therapy (JAMA Surgery 2015 June 17 [doi:10.1001/jamasurg.2015.1102]).

The researchers declared no conflicts of interest.

The rates of breast-conserving surgery have increased over the last 2 decades among women with early-stage breast cancers in the United States, but disparities persist, based on an analysis of data from the National Cancer Data Base.

The rate of breast-conserving surgery has risen from approximately 54% in 1998 to 60% in 2011, but this rate may have been affected by “technical advances and changes in societal norms [that] include genetic testing for BRCA1 and BRCA2 mutation, advances in reconstruction techniques, breast magnetic resonance imaging, and increased patient interest in contralateral prophylactic mastectomy,” Dr. Meeghan Lautner and her colleagues at University of Texas MD Anderson Cancer Care Center, Houston, wrote.

“Among the most encouraging findings from our analysis is the considerable improvement of disparities based on facility type and the options afforded to older populations … however, insurance, income, and travel distance to treatment facilities persist as key barriers to [breast-conserving therapy] use,” the researchers said.

Their analysis of a cohort of 727,927 women, published online June 17 in JAMA Surgery, showed that women with early breast cancer were less likely to receive breast-conserving surgery if they had a low educational level, public or no health insurance, and low income.

Women aged 52-61 years were 14% more likely to be treated with breast-conserving surgery, compared with younger women. White race, fewer comorbidities, and living closer to a treatment facility were all positively associated with being treated with breast-conserving surgery.

Those in southern regions of the United States were significantly less likely to receive breast-conserving surgery, compared with those in the Northeast. The researchers said their data suggest the lower rates are because of the greater travel distances to treatment facilities in the South.

Women with no insurance were 25% less likely than those with private insurance to have breast-conserving therapy (JAMA Surgery 2015 June 17 [doi:10.1001/jamasurg.2015.1102]).

The researchers declared no conflicts of interest.

CHICAGO – Homologous recombination (HR) deficiency is a biomarker for benefit from neoadjuvant chemotherapy in women with triple-negative breast cancer (TNBC), suggest data from the GeparSixto trial presented at the annual meeting of the American Society of Clinical Oncology.

Roughly two-thirds of women were found to have HR-deficient tumors, impairing their ability to repair DNA and thereby rendering them susceptible to DNA-damaging agents. These women had more than double the odds of a pathologic complete response (pCR).

“HR deficiency in triple-negative breast cancer appears to be an independent predictor of high pCR rates to the chemotherapies that were given in this study,” summarized Dr. Gunter von Minckwitz on behalf of the German Breast Group and Arbeitsgemeinschaft Gynakologische Onkologie-B (AGO-B) study group.

However, the findings were somewhat inconsistent. Additionally, although the highest pCR rate, at about 65%, was seen in women who had HR-deficient tumors and received carboplatin, women whose tumors were nondeficient also had some benefit from addition of this agent.

“This is why these data have to be confirmed by other studies, for example, the same measurements are currently ongoing in the CALGB 40603 study,” commented Dr. von Minckwitz, a senior physician at the University Women’s Hospital in Frankfurt. “And finally, they have to be set into the context with survival data that we expect at the end of 2015 or beginning of 2016.”

Invited discussant Dr. Pamela N. Munster, a professor at the University of California, San Francisco, noted, “Homologous recombination deficiency mediated through the host or tumor predicts for high responses to chemotherapy and platinum salts in early-stage triple-negative breast cancer.” However, “the role of carboplatin and its optimal setting remains complex.”

She asked about the prevailing clinical practice regarding this agent’s use. “Based on your presentation and your work, what’s the landscape in Europe on the incorporation of carboplatin in the neoadjuvant therapy in triple-negative breast cancer or a subselect group?”

“We made a survey in our group half a year ago, and all members said that they are using carboplatin in triple-negative disease when they get neoadjuvant treatment,” Dr. von Minckwitz replied. “I’m not sure if this was 100% of patients, but I believe it was a more general quote, and this is in concordance with our AGO guideline, which allows the use of carboplatin in general in triple-negative [breast cancer]. It still says in patients with germline mutations, there is a somewhat stronger recommendation to use it, but it’s of course not a must.”

Session attendee Dr. Rebecca Dent of the National Cancer Centre Singapore and the University of Toronto asked whether oncologists should begin clinically applying HR deficiency for patient selection.

“I don’t think that currently these data or the sample size is sufficient to support clinical use tomorrow. … We have to wait for a confirmative study,” Dr. von Minckwitz replied.

Dr. Munster, the discussant, agreed, saying, “I think the HRD percentage is actually quite high in [this] set, so the test may not be as robust as we like to see. So I think part of it is refinement of biomarkers has to be the focus of what we do in the next 10 years.”

Previous results of the randomized phase 2/3 GeparSixto trial have shown that adding carboplatin to a neoadjuvant chemotherapy backbone (paclitaxel, liposomal doxorubicin, and bevacizumab) improves the pCR rate in patients with triple-negative breast cancer, but at the cost of added toxicity (Lancet Oncol. 2014;15:747-56). “Therefore it is of importance to better define the group of patients that might have a higher benefit from the addition of carboplatin,” Dr. von Minckwitz explained.

“We know from previous studies that tumors with a decreased DNA repair capacity, for example, due to a mutation of the BRCA1 or BRCA2 gene are expected to have a higher sensitivity to DNA-damaging agents like platinum compounds. A more extensive way to measure DNA repair capacity is now possible using the HRD assay,” he noted.

The investigators assessed tumor HR deficiency among the 315 trial participants with triple-negative breast cancer. Overall, 70.5% had tumors that were HR deficient (meaning they had a high HRD score or a tumor BRCA mutation).

In the entire cohort, women with HR-deficient tumors were more likely to have a pCR, defined as absence of invasive residual disease in the breast or nodes (ypT0/is ypN0), than peers with HR-nondeficient tumors (55.9% vs. 29.8%). In multivariate analysis, HR deficiency independently predicted pCR (odds ratio, 2.51; P = .009).

Adding carboplatin improved the pCR rate significantly in women who had HR-deficient tumors (from 45.2% to 64.9%, P = .025) but also somewhat in women who had HR-nondeficient tumors (from 20.0% and 40.7%, P = .146). And there was no significant interaction between HR deficiency and carboplatin benefit.

In further analyses, carboplatin had a significant benefit in patients with a high HRD score but intact tumor BRCA, but not in patients with mutated tumor BRCA.

Findings differed slightly when the investigators repeated analyses but instead used a stricter definition of pCR that calls for absence of both invasive and noninvasive (ductal carcinoma in situ) residual disease in the breast and nodes (ypT0 ypN0), according to Dr. von Minckwitz.

Given that the majority of HR-deficient tumors did not have a BRCA mutation, the investigators plan to assess other drivers of HR deficiency, he said.

Dr. von Minckwitz disclosed employment, leadership, and stock ownership relationships with GBG Forschungs GmbH and research funding to his institution by Amgen, AstraZeneca, Boehringer Ingelheim, Celgene, GlaxoSmithKline, Novartis, Pfizer, Roche, Sanofi, and Teva. The trial was funded by Teva, Roche Pharma AG, and GlaxoSmithKline.

CHICAGO – Homologous recombination (HR) deficiency is a biomarker for benefit from neoadjuvant chemotherapy in women with triple-negative breast cancer (TNBC), suggest data from the GeparSixto trial presented at the annual meeting of the American Society of Clinical Oncology.

Roughly two-thirds of women were found to have HR-deficient tumors, impairing their ability to repair DNA and thereby rendering them susceptible to DNA-damaging agents. These women had more than double the odds of a pathologic complete response (pCR).

“HR deficiency in triple-negative breast cancer appears to be an independent predictor of high pCR rates to the chemotherapies that were given in this study,” summarized Dr. Gunter von Minckwitz on behalf of the German Breast Group and Arbeitsgemeinschaft Gynakologische Onkologie-B (AGO-B) study group.

However, the findings were somewhat inconsistent. Additionally, although the highest pCR rate, at about 65%, was seen in women who had HR-deficient tumors and received carboplatin, women whose tumors were nondeficient also had some benefit from addition of this agent.

“This is why these data have to be confirmed by other studies, for example, the same measurements are currently ongoing in the CALGB 40603 study,” commented Dr. von Minckwitz, a senior physician at the University Women’s Hospital in Frankfurt. “And finally, they have to be set into the context with survival data that we expect at the end of 2015 or beginning of 2016.”

Invited discussant Dr. Pamela N. Munster, a professor at the University of California, San Francisco, noted, “Homologous recombination deficiency mediated through the host or tumor predicts for high responses to chemotherapy and platinum salts in early-stage triple-negative breast cancer.” However, “the role of carboplatin and its optimal setting remains complex.”

She asked about the prevailing clinical practice regarding this agent’s use. “Based on your presentation and your work, what’s the landscape in Europe on the incorporation of carboplatin in the neoadjuvant therapy in triple-negative breast cancer or a subselect group?”

“We made a survey in our group half a year ago, and all members said that they are using carboplatin in triple-negative disease when they get neoadjuvant treatment,” Dr. von Minckwitz replied. “I’m not sure if this was 100% of patients, but I believe it was a more general quote, and this is in concordance with our AGO guideline, which allows the use of carboplatin in general in triple-negative [breast cancer]. It still says in patients with germline mutations, there is a somewhat stronger recommendation to use it, but it’s of course not a must.”

Session attendee Dr. Rebecca Dent of the National Cancer Centre Singapore and the University of Toronto asked whether oncologists should begin clinically applying HR deficiency for patient selection.

“I don’t think that currently these data or the sample size is sufficient to support clinical use tomorrow. … We have to wait for a confirmative study,” Dr. von Minckwitz replied.

Dr. Munster, the discussant, agreed, saying, “I think the HRD percentage is actually quite high in [this] set, so the test may not be as robust as we like to see. So I think part of it is refinement of biomarkers has to be the focus of what we do in the next 10 years.”

Previous results of the randomized phase 2/3 GeparSixto trial have shown that adding carboplatin to a neoadjuvant chemotherapy backbone (paclitaxel, liposomal doxorubicin, and bevacizumab) improves the pCR rate in patients with triple-negative breast cancer, but at the cost of added toxicity (Lancet Oncol. 2014;15:747-56). “Therefore it is of importance to better define the group of patients that might have a higher benefit from the addition of carboplatin,” Dr. von Minckwitz explained.

“We know from previous studies that tumors with a decreased DNA repair capacity, for example, due to a mutation of the BRCA1 or BRCA2 gene are expected to have a higher sensitivity to DNA-damaging agents like platinum compounds. A more extensive way to measure DNA repair capacity is now possible using the HRD assay,” he noted.

The investigators assessed tumor HR deficiency among the 315 trial participants with triple-negative breast cancer. Overall, 70.5% had tumors that were HR deficient (meaning they had a high HRD score or a tumor BRCA mutation).

In the entire cohort, women with HR-deficient tumors were more likely to have a pCR, defined as absence of invasive residual disease in the breast or nodes (ypT0/is ypN0), than peers with HR-nondeficient tumors (55.9% vs. 29.8%). In multivariate analysis, HR deficiency independently predicted pCR (odds ratio, 2.51; P = .009).

Adding carboplatin improved the pCR rate significantly in women who had HR-deficient tumors (from 45.2% to 64.9%, P = .025) but also somewhat in women who had HR-nondeficient tumors (from 20.0% and 40.7%, P = .146). And there was no significant interaction between HR deficiency and carboplatin benefit.

In further analyses, carboplatin had a significant benefit in patients with a high HRD score but intact tumor BRCA, but not in patients with mutated tumor BRCA.

Findings differed slightly when the investigators repeated analyses but instead used a stricter definition of pCR that calls for absence of both invasive and noninvasive (ductal carcinoma in situ) residual disease in the breast and nodes (ypT0 ypN0), according to Dr. von Minckwitz.

Given that the majority of HR-deficient tumors did not have a BRCA mutation, the investigators plan to assess other drivers of HR deficiency, he said.

Dr. von Minckwitz disclosed employment, leadership, and stock ownership relationships with GBG Forschungs GmbH and research funding to his institution by Amgen, AstraZeneca, Boehringer Ingelheim, Celgene, GlaxoSmithKline, Novartis, Pfizer, Roche, Sanofi, and Teva. The trial was funded by Teva, Roche Pharma AG, and GlaxoSmithKline.

CHICAGO – Homologous recombination (HR) deficiency is a biomarker for benefit from neoadjuvant chemotherapy in women with triple-negative breast cancer (TNBC), suggest data from the GeparSixto trial presented at the annual meeting of the American Society of Clinical Oncology.

Roughly two-thirds of women were found to have HR-deficient tumors, impairing their ability to repair DNA and thereby rendering them susceptible to DNA-damaging agents. These women had more than double the odds of a pathologic complete response (pCR).

“HR deficiency in triple-negative breast cancer appears to be an independent predictor of high pCR rates to the chemotherapies that were given in this study,” summarized Dr. Gunter von Minckwitz on behalf of the German Breast Group and Arbeitsgemeinschaft Gynakologische Onkologie-B (AGO-B) study group.

However, the findings were somewhat inconsistent. Additionally, although the highest pCR rate, at about 65%, was seen in women who had HR-deficient tumors and received carboplatin, women whose tumors were nondeficient also had some benefit from addition of this agent.

“This is why these data have to be confirmed by other studies, for example, the same measurements are currently ongoing in the CALGB 40603 study,” commented Dr. von Minckwitz, a senior physician at the University Women’s Hospital in Frankfurt. “And finally, they have to be set into the context with survival data that we expect at the end of 2015 or beginning of 2016.”

Invited discussant Dr. Pamela N. Munster, a professor at the University of California, San Francisco, noted, “Homologous recombination deficiency mediated through the host or tumor predicts for high responses to chemotherapy and platinum salts in early-stage triple-negative breast cancer.” However, “the role of carboplatin and its optimal setting remains complex.”

She asked about the prevailing clinical practice regarding this agent’s use. “Based on your presentation and your work, what’s the landscape in Europe on the incorporation of carboplatin in the neoadjuvant therapy in triple-negative breast cancer or a subselect group?”

“We made a survey in our group half a year ago, and all members said that they are using carboplatin in triple-negative disease when they get neoadjuvant treatment,” Dr. von Minckwitz replied. “I’m not sure if this was 100% of patients, but I believe it was a more general quote, and this is in concordance with our AGO guideline, which allows the use of carboplatin in general in triple-negative [breast cancer]. It still says in patients with germline mutations, there is a somewhat stronger recommendation to use it, but it’s of course not a must.”

Session attendee Dr. Rebecca Dent of the National Cancer Centre Singapore and the University of Toronto asked whether oncologists should begin clinically applying HR deficiency for patient selection.

“I don’t think that currently these data or the sample size is sufficient to support clinical use tomorrow. … We have to wait for a confirmative study,” Dr. von Minckwitz replied.

Dr. Munster, the discussant, agreed, saying, “I think the HRD percentage is actually quite high in [this] set, so the test may not be as robust as we like to see. So I think part of it is refinement of biomarkers has to be the focus of what we do in the next 10 years.”

Previous results of the randomized phase 2/3 GeparSixto trial have shown that adding carboplatin to a neoadjuvant chemotherapy backbone (paclitaxel, liposomal doxorubicin, and bevacizumab) improves the pCR rate in patients with triple-negative breast cancer, but at the cost of added toxicity (Lancet Oncol. 2014;15:747-56). “Therefore it is of importance to better define the group of patients that might have a higher benefit from the addition of carboplatin,” Dr. von Minckwitz explained.

“We know from previous studies that tumors with a decreased DNA repair capacity, for example, due to a mutation of the BRCA1 or BRCA2 gene are expected to have a higher sensitivity to DNA-damaging agents like platinum compounds. A more extensive way to measure DNA repair capacity is now possible using the HRD assay,” he noted.

The investigators assessed tumor HR deficiency among the 315 trial participants with triple-negative breast cancer. Overall, 70.5% had tumors that were HR deficient (meaning they had a high HRD score or a tumor BRCA mutation).

In the entire cohort, women with HR-deficient tumors were more likely to have a pCR, defined as absence of invasive residual disease in the breast or nodes (ypT0/is ypN0), than peers with HR-nondeficient tumors (55.9% vs. 29.8%). In multivariate analysis, HR deficiency independently predicted pCR (odds ratio, 2.51; P = .009).

Adding carboplatin improved the pCR rate significantly in women who had HR-deficient tumors (from 45.2% to 64.9%, P = .025) but also somewhat in women who had HR-nondeficient tumors (from 20.0% and 40.7%, P = .146). And there was no significant interaction between HR deficiency and carboplatin benefit.

In further analyses, carboplatin had a significant benefit in patients with a high HRD score but intact tumor BRCA, but not in patients with mutated tumor BRCA.

Findings differed slightly when the investigators repeated analyses but instead used a stricter definition of pCR that calls for absence of both invasive and noninvasive (ductal carcinoma in situ) residual disease in the breast and nodes (ypT0 ypN0), according to Dr. von Minckwitz.

Given that the majority of HR-deficient tumors did not have a BRCA mutation, the investigators plan to assess other drivers of HR deficiency, he said.

Dr. von Minckwitz disclosed employment, leadership, and stock ownership relationships with GBG Forschungs GmbH and research funding to his institution by Amgen, AstraZeneca, Boehringer Ingelheim, Celgene, GlaxoSmithKline, Novartis, Pfizer, Roche, Sanofi, and Teva. The trial was funded by Teva, Roche Pharma AG, and GlaxoSmithKline.

CHICAGO – Anastrozole may top tamoxifen in reducing the risk of disease recurrence in postmenopausal ductal carcinoma in situ (DCIS), particularly in younger women, but which drug holds a cost advantage?

“How much do you want to pay in dollars or in side effects to achieve the extra benefit is an individual decision that a woman has to make with her physician,” said Dr. Richard Margolese, professor of surgical oncology at Jewish General Hospital, McGill University, Montreal.

In a video interview at the annual meeting of the American Society of Clinical Oncology, Dr. Margolese discussed the cost and side effect considerations that could determine a decision between anastrozole and tamoxifen.

trudd@frontlinemedcom.com

CHICAGO – Anastrozole may top tamoxifen in reducing the risk of disease recurrence in postmenopausal ductal carcinoma in situ (DCIS), particularly in younger women, but which drug holds a cost advantage?

“How much do you want to pay in dollars or in side effects to achieve the extra benefit is an individual decision that a woman has to make with her physician,” said Dr. Richard Margolese, professor of surgical oncology at Jewish General Hospital, McGill University, Montreal.

In a video interview at the annual meeting of the American Society of Clinical Oncology, Dr. Margolese discussed the cost and side effect considerations that could determine a decision between anastrozole and tamoxifen.

trudd@frontlinemedcom.com

CHICAGO – Anastrozole may top tamoxifen in reducing the risk of disease recurrence in postmenopausal ductal carcinoma in situ (DCIS), particularly in younger women, but which drug holds a cost advantage?

“How much do you want to pay in dollars or in side effects to achieve the extra benefit is an individual decision that a woman has to make with her physician,” said Dr. Richard Margolese, professor of surgical oncology at Jewish General Hospital, McGill University, Montreal.

In a video interview at the annual meeting of the American Society of Clinical Oncology, Dr. Margolese discussed the cost and side effect considerations that could determine a decision between anastrozole and tamoxifen.

trudd@frontlinemedcom.com

Women who are overweight and obese have a significantly higher risk of invasive breast cancer after menopause compared with normal-weight women, according to secondary analysis of data from the Women’s Health Initiative.

An analysis of data from 67,142 postmenopausal women aged 50-79 years found that women with a body mass index greater than 35 had a 58% increased risk of invasive breast cancer, compared with women with a BMI lower than 25. Obese women with a BMI of greater than 35 were also at increased risk for estrogen- and progesterone-receptor–positive breast cancer compared to normal-weight women (hazard ratio, 1.86), but they were not at increased risk for hormone receptor–negative breast cancer.

Dr. Cecil Fox/National Cancer Institute

This group also had a twofold increase in the risk of being diagnosed with a larger tumor, and significantly higher risk of having positive lymph nodes, regional and/or distant stage, and also of dying after breast cancer, according to an article published June 11 in JAMA Oncology.

“Well-designed clinical trials are needed to definitively test whether weight loss and body composition changes in overweight and obese women or obesity prevention in women of normal weight will reduce breast cancer risk,” wrote Marian L. Neuhouser, Ph.D., of the Fred Hutchinson Cancer Research Center in Seattle, and her colleagues (JAMA Oncol. 2015. June 11 [doi: 10.1001/jamaoncol. 2015.1546]).

The Women’s Health Initiative programs are supported by the National Heart, Lung, and Blood Institute, part of the National Institutes of Health. One of the researchers disclosed having financial relationships with Novartis, Novo Nordisk, Pfizer, Genetech, and Amgen. The other researchers reported having no financial disclosures.

Women who are overweight and obese have a significantly higher risk of invasive breast cancer after menopause compared with normal-weight women, according to secondary analysis of data from the Women’s Health Initiative.

An analysis of data from 67,142 postmenopausal women aged 50-79 years found that women with a body mass index greater than 35 had a 58% increased risk of invasive breast cancer, compared with women with a BMI lower than 25. Obese women with a BMI of greater than 35 were also at increased risk for estrogen- and progesterone-receptor–positive breast cancer compared to normal-weight women (hazard ratio, 1.86), but they were not at increased risk for hormone receptor–negative breast cancer.

Dr. Cecil Fox/National Cancer Institute

This group also had a twofold increase in the risk of being diagnosed with a larger tumor, and significantly higher risk of having positive lymph nodes, regional and/or distant stage, and also of dying after breast cancer, according to an article published June 11 in JAMA Oncology.

“Well-designed clinical trials are needed to definitively test whether weight loss and body composition changes in overweight and obese women or obesity prevention in women of normal weight will reduce breast cancer risk,” wrote Marian L. Neuhouser, Ph.D., of the Fred Hutchinson Cancer Research Center in Seattle, and her colleagues (JAMA Oncol. 2015. June 11 [doi: 10.1001/jamaoncol. 2015.1546]).

The Women’s Health Initiative programs are supported by the National Heart, Lung, and Blood Institute, part of the National Institutes of Health. One of the researchers disclosed having financial relationships with Novartis, Novo Nordisk, Pfizer, Genetech, and Amgen. The other researchers reported having no financial disclosures.

Women who are overweight and obese have a significantly higher risk of invasive breast cancer after menopause compared with normal-weight women, according to secondary analysis of data from the Women’s Health Initiative.

An analysis of data from 67,142 postmenopausal women aged 50-79 years found that women with a body mass index greater than 35 had a 58% increased risk of invasive breast cancer, compared with women with a BMI lower than 25. Obese women with a BMI of greater than 35 were also at increased risk for estrogen- and progesterone-receptor–positive breast cancer compared to normal-weight women (hazard ratio, 1.86), but they were not at increased risk for hormone receptor–negative breast cancer.

Dr. Cecil Fox/National Cancer Institute

This group also had a twofold increase in the risk of being diagnosed with a larger tumor, and significantly higher risk of having positive lymph nodes, regional and/or distant stage, and also of dying after breast cancer, according to an article published June 11 in JAMA Oncology.

“Well-designed clinical trials are needed to definitively test whether weight loss and body composition changes in overweight and obese women or obesity prevention in women of normal weight will reduce breast cancer risk,” wrote Marian L. Neuhouser, Ph.D., of the Fred Hutchinson Cancer Research Center in Seattle, and her colleagues (JAMA Oncol. 2015. June 11 [doi: 10.1001/jamaoncol. 2015.1546]).

The Women’s Health Initiative programs are supported by the National Heart, Lung, and Blood Institute, part of the National Institutes of Health. One of the researchers disclosed having financial relationships with Novartis, Novo Nordisk, Pfizer, Genetech, and Amgen. The other researchers reported having no financial disclosures.

CHICAGO – Etirinotecan pegol is an efficacious treatment option for selected women with heavily pretreated advanced breast cancer, suggests the international phase III BEACON study (Breast Cancer Outcomes With NKTR-102).

Compared with a treatment of the physician’s choice, the novel drug – an encapsulated form of irinotecan that inhibits topoisomerase 1—did not significantly improve overall survival in the trial population as a whole, first author Dr. Edith A. Perez reported at the annual meeting of the American Society of Clinical Oncology. But it reduced the risk of death by nearly half for the subset of women with a history of brain metastases and by more than a quarter for the subset of women with a history of liver metastases, with less toxicity and better quality of life.

“Etirinotecan pegol … [has] clinical activity and good tolerability in patients with heavily pretreated advanced breast cancer,” summarized Dr. Perez, who is deputy director at large for the Mayo Clinic Cancer Center in Jacksonville, Florida, as well as director of the Mayo Clinic Breast Cancer Translational Genomics Program and chair of the Breast Cancer Specialty Council.

“The 2.1-month improvement in median survival favoring etirinotecan pegol did not reach statistical significance. However, provocative and potentially very important survival results in predefined subgroups of patients deserve further study, specifically, patients with brain metastases or liver metastases,” she said. “Exploration of potential predictive biomarkers is ongoing.”

The findings regarding brain metastases are “an intriguing nugget,” according to invited discussant Dr. Harold J. Burstein, a senior physician at the Dana-Farber Cancer Institute and an associate professor of medicine at Harvard Medical School, both in Boston. “I think these data and the growing literature on the effectiveness of systemic therapy for brain metastases … suggest that it’s time for us to be doing trials where we are comparing standards of care of radiotherapy against chemotherapy, trying to optimize our chemotherapy regimens for the palliation of metastatic disease of the brain.”

He pointed to a set of trials in patients with advanced lung cancer testing the benefits of early palliative care on outcomes and finding improvements in overall survival or in quality of life with no detriment to overall survival.

“I used to look at these and think this didn’t really speak to the breast cancer population. But when you start to see data in the heavily refractory patients as we have observed today, it turns out that their survival is unfortunately essentially the same as for all the patients who participated in these trials,” he said. “So when we think about what direction we should go for advanced breast cancer that’s heavily refractory to chemotherapy, in addition to exploring a variety of exciting new immunologic therapies, and targeted therapies … I think we need to begin to lean more on our palliation care specialists and colleagues to help us truly take optimal care of these patients.”

The 852 women studied in the BEACON trial had experienced progression after anthracycline, taxane, and capecitabine therapy and had received two to five prior therapies for their advanced disease. The trial, sponsored by Nektar Therapeutics, was unusual in that it allowed patients with stable brain metastases to enroll and set a high bar of overall survival as its primary endpoint, Dr. Perez noted.

The patients were randomized evenly to receive single-agent etirinotecan pegol or a single agent of the physician’s choice, which was most commonly eribulin.

Main results showed no significant improvement in overall survival among the entire trial population comparing etirinotecan pegol with physician’s choice (12.4 vs. 10.3 months; hazard ratio, 0.87; P = .08).

However, preplanned subgroup analyses showed that in the 8% of women who had a history of brain metastases, median overall survival was 10.0 months with the drug and 4.8 months with physician’s choice (HR, 0.51; P = .0099). The curves began to separate within 3 months of randomization, and the difference in the proportion of women alive at 12 months was “pretty amazing,” Dr. Perez noted, at 44% versus 19%.

There was a similar although smaller survival advantage of etirinotecan pegol among the 53% of patients with a history of liver metastases (10.9 vs. 8.3 months; HR, 0.73; P = .002).

A variety of biomarkers for etirinotecan benefit are still being analyzed, according to Dr. Perez. The most promising signal thus far has been a reduction in the number of topoisomerase 1–positive circulating tumor cells, with patients going from high (above the baseline median) to low (below the baseline median) numbers surviving significantly longer than peers having persistently high numbers (14.9 vs. 10.7 months; HR, 0.54; P = .007).

The rate of grade 3 or worse toxicity was lower with etirinotecan pegol than with physician’s choice (48% vs. 63%). The former was associated with a higher rate of diarrhea, whereas the latter was associated with higher rates of neutropenia and peripheral neuropathy.

Patients in the etirinotecan pegol group had a more favorable change from baseline in global health status and in physical functioning, reported Dr. Perez.

CHICAGO – Etirinotecan pegol is an efficacious treatment option for selected women with heavily pretreated advanced breast cancer, suggests the international phase III BEACON study (Breast Cancer Outcomes With NKTR-102).

Compared with a treatment of the physician’s choice, the novel drug – an encapsulated form of irinotecan that inhibits topoisomerase 1—did not significantly improve overall survival in the trial population as a whole, first author Dr. Edith A. Perez reported at the annual meeting of the American Society of Clinical Oncology. But it reduced the risk of death by nearly half for the subset of women with a history of brain metastases and by more than a quarter for the subset of women with a history of liver metastases, with less toxicity and better quality of life.

“Etirinotecan pegol … [has] clinical activity and good tolerability in patients with heavily pretreated advanced breast cancer,” summarized Dr. Perez, who is deputy director at large for the Mayo Clinic Cancer Center in Jacksonville, Florida, as well as director of the Mayo Clinic Breast Cancer Translational Genomics Program and chair of the Breast Cancer Specialty Council.

“The 2.1-month improvement in median survival favoring etirinotecan pegol did not reach statistical significance. However, provocative and potentially very important survival results in predefined subgroups of patients deserve further study, specifically, patients with brain metastases or liver metastases,” she said. “Exploration of potential predictive biomarkers is ongoing.”

The findings regarding brain metastases are “an intriguing nugget,” according to invited discussant Dr. Harold J. Burstein, a senior physician at the Dana-Farber Cancer Institute and an associate professor of medicine at Harvard Medical School, both in Boston. “I think these data and the growing literature on the effectiveness of systemic therapy for brain metastases … suggest that it’s time for us to be doing trials where we are comparing standards of care of radiotherapy against chemotherapy, trying to optimize our chemotherapy regimens for the palliation of metastatic disease of the brain.”

He pointed to a set of trials in patients with advanced lung cancer testing the benefits of early palliative care on outcomes and finding improvements in overall survival or in quality of life with no detriment to overall survival.

“I used to look at these and think this didn’t really speak to the breast cancer population. But when you start to see data in the heavily refractory patients as we have observed today, it turns out that their survival is unfortunately essentially the same as for all the patients who participated in these trials,” he said. “So when we think about what direction we should go for advanced breast cancer that’s heavily refractory to chemotherapy, in addition to exploring a variety of exciting new immunologic therapies, and targeted therapies … I think we need to begin to lean more on our palliation care specialists and colleagues to help us truly take optimal care of these patients.”

The 852 women studied in the BEACON trial had experienced progression after anthracycline, taxane, and capecitabine therapy and had received two to five prior therapies for their advanced disease. The trial, sponsored by Nektar Therapeutics, was unusual in that it allowed patients with stable brain metastases to enroll and set a high bar of overall survival as its primary endpoint, Dr. Perez noted.

The patients were randomized evenly to receive single-agent etirinotecan pegol or a single agent of the physician’s choice, which was most commonly eribulin.

Main results showed no significant improvement in overall survival among the entire trial population comparing etirinotecan pegol with physician’s choice (12.4 vs. 10.3 months; hazard ratio, 0.87; P = .08).

However, preplanned subgroup analyses showed that in the 8% of women who had a history of brain metastases, median overall survival was 10.0 months with the drug and 4.8 months with physician’s choice (HR, 0.51; P = .0099). The curves began to separate within 3 months of randomization, and the difference in the proportion of women alive at 12 months was “pretty amazing,” Dr. Perez noted, at 44% versus 19%.

There was a similar although smaller survival advantage of etirinotecan pegol among the 53% of patients with a history of liver metastases (10.9 vs. 8.3 months; HR, 0.73; P = .002).

A variety of biomarkers for etirinotecan benefit are still being analyzed, according to Dr. Perez. The most promising signal thus far has been a reduction in the number of topoisomerase 1–positive circulating tumor cells, with patients going from high (above the baseline median) to low (below the baseline median) numbers surviving significantly longer than peers having persistently high numbers (14.9 vs. 10.7 months; HR, 0.54; P = .007).

The rate of grade 3 or worse toxicity was lower with etirinotecan pegol than with physician’s choice (48% vs. 63%). The former was associated with a higher rate of diarrhea, whereas the latter was associated with higher rates of neutropenia and peripheral neuropathy.

Patients in the etirinotecan pegol group had a more favorable change from baseline in global health status and in physical functioning, reported Dr. Perez.

CHICAGO – Etirinotecan pegol is an efficacious treatment option for selected women with heavily pretreated advanced breast cancer, suggests the international phase III BEACON study (Breast Cancer Outcomes With NKTR-102).

Compared with a treatment of the physician’s choice, the novel drug – an encapsulated form of irinotecan that inhibits topoisomerase 1—did not significantly improve overall survival in the trial population as a whole, first author Dr. Edith A. Perez reported at the annual meeting of the American Society of Clinical Oncology. But it reduced the risk of death by nearly half for the subset of women with a history of brain metastases and by more than a quarter for the subset of women with a history of liver metastases, with less toxicity and better quality of life.

“Etirinotecan pegol … [has] clinical activity and good tolerability in patients with heavily pretreated advanced breast cancer,” summarized Dr. Perez, who is deputy director at large for the Mayo Clinic Cancer Center in Jacksonville, Florida, as well as director of the Mayo Clinic Breast Cancer Translational Genomics Program and chair of the Breast Cancer Specialty Council.

“The 2.1-month improvement in median survival favoring etirinotecan pegol did not reach statistical significance. However, provocative and potentially very important survival results in predefined subgroups of patients deserve further study, specifically, patients with brain metastases or liver metastases,” she said. “Exploration of potential predictive biomarkers is ongoing.”

The findings regarding brain metastases are “an intriguing nugget,” according to invited discussant Dr. Harold J. Burstein, a senior physician at the Dana-Farber Cancer Institute and an associate professor of medicine at Harvard Medical School, both in Boston. “I think these data and the growing literature on the effectiveness of systemic therapy for brain metastases … suggest that it’s time for us to be doing trials where we are comparing standards of care of radiotherapy against chemotherapy, trying to optimize our chemotherapy regimens for the palliation of metastatic disease of the brain.”

He pointed to a set of trials in patients with advanced lung cancer testing the benefits of early palliative care on outcomes and finding improvements in overall survival or in quality of life with no detriment to overall survival.

“I used to look at these and think this didn’t really speak to the breast cancer population. But when you start to see data in the heavily refractory patients as we have observed today, it turns out that their survival is unfortunately essentially the same as for all the patients who participated in these trials,” he said. “So when we think about what direction we should go for advanced breast cancer that’s heavily refractory to chemotherapy, in addition to exploring a variety of exciting new immunologic therapies, and targeted therapies … I think we need to begin to lean more on our palliation care specialists and colleagues to help us truly take optimal care of these patients.”

The 852 women studied in the BEACON trial had experienced progression after anthracycline, taxane, and capecitabine therapy and had received two to five prior therapies for their advanced disease. The trial, sponsored by Nektar Therapeutics, was unusual in that it allowed patients with stable brain metastases to enroll and set a high bar of overall survival as its primary endpoint, Dr. Perez noted.

The patients were randomized evenly to receive single-agent etirinotecan pegol or a single agent of the physician’s choice, which was most commonly eribulin.

Main results showed no significant improvement in overall survival among the entire trial population comparing etirinotecan pegol with physician’s choice (12.4 vs. 10.3 months; hazard ratio, 0.87; P = .08).

However, preplanned subgroup analyses showed that in the 8% of women who had a history of brain metastases, median overall survival was 10.0 months with the drug and 4.8 months with physician’s choice (HR, 0.51; P = .0099). The curves began to separate within 3 months of randomization, and the difference in the proportion of women alive at 12 months was “pretty amazing,” Dr. Perez noted, at 44% versus 19%.

There was a similar although smaller survival advantage of etirinotecan pegol among the 53% of patients with a history of liver metastases (10.9 vs. 8.3 months; HR, 0.73; P = .002).

A variety of biomarkers for etirinotecan benefit are still being analyzed, according to Dr. Perez. The most promising signal thus far has been a reduction in the number of topoisomerase 1–positive circulating tumor cells, with patients going from high (above the baseline median) to low (below the baseline median) numbers surviving significantly longer than peers having persistently high numbers (14.9 vs. 10.7 months; HR, 0.54; P = .007).

The rate of grade 3 or worse toxicity was lower with etirinotecan pegol than with physician’s choice (48% vs. 63%). The former was associated with a higher rate of diarrhea, whereas the latter was associated with higher rates of neutropenia and peripheral neuropathy.

Patients in the etirinotecan pegol group had a more favorable change from baseline in global health status and in physical functioning, reported Dr. Perez.

CHICAGO – Women with breast cancer treated with neoadjuvant chemotherapy and surgery are more likely to have a recurrence in the breast, chest wall, or axilla or to die if they don’t receive adjuvant radiation therapy, even if they had a pathologic complete response to the chemotherapy, new data show.

In a meta-analysis of three Gepar trials conducted by the German Breast Group, radiation therapy was associated with a 38% lower multivariate risk of locoregional recurrence or death, investigators reported at the annual meeting of the American Society of Clinical Oncology. Significant benefit was seen regardless of pathologic complete response, although findings across other subgroups were not consistent, possibly due to selection bias or underlying confounders.

“Radiotherapy is an independent prognostic factor for locoregional recurrence–free survival after neoadjuvant chemotherapy in breast cancer. However, the optimal selection criteria remain unclear,” commented first author Dr. David Krug of University Hospital Heidelberg (Germany).

“We are eagerly awaiting the results of prospective studies that are currently recruiting patients,” he added, referring to the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-51 trial and the Radiotherapy After Primary Chemotherapy for Breast Cancer (RAPCHEM) trial.

Findings of this meta-analysis are not practice changing, according to invited discussant Dr. Monica Morrow, chief of the breast service, department of surgery, and the Anne Burnett Windfohr Chair of Clinical Oncology at the Memorial Sloan Kettering Cancer Center in New York. “The Gepar data is not consistent enough across subsets to draw any different conclusions other than we need more data,” she said.

Focusing on the women who underwent mastectomy, she noted that only a small number who had a pathologic complete response did not receive radiation therapy, “so this study unfortunately lacks the power to tell us anything about the ability to eliminate radiation in this group.”

“What we’d really like to know about local control after neoadjuvant therapy is what’s the relative contribution of pretreatment stage and posttreatment stage to the risk of locoregional recurrence, especially in patients who achieve pathologic complete response? And if we try to address that question with this study, the results were a little murky,” Dr. Morrow further noted. For example, patients with higher–T stage primary tumors benefited from postmastectomy radiation, but patients who were clinically node positive did not.

“I think right now, what we have to say is we need to continue to do what we have been doing up until the present time, namely, patients whose presenting stage clearly indicates the need for radiotherapy should receive it, and patients who have lower-stage disease perhaps not,” she concluded, agreeing that the NSABP B-51 trial should help put this issue to rest.

Dr. Krug and his colleagues performed a pooled meta-analysis of data from the GeparTrio, GeparQuattro, and GeparQuinto trials of neoadjuvant chemotherapy, in which guidelines specified when adjuvant radiation therapy should be used. Those guidelines called for whole-breast radiation therapy with a boost after breast-conserving surgery (with omission of the boost in low-risk patients); radiation therapy after mastectomy for patients having more extensive disease before neoadjuvant chemotherapy; and radiation therapy for those with greater involvement of the regional lymphatics.

The meta-analysis was based on a total of 3,370 women. Overall, 94% received radiation therapy (99% of those who had undergone breast-conserving surgery and 85% of those who had undergone mastectomy).

With a median follow-up of 4.2 years, the 5-year rate of locoregional recurrence–free survival was 89.2% in the entire study population, according to Dr. Krug.

Women who did not receive radiation therapy had a significantly elevated risk of such recurrence or death compared with peers who received it. In subgroups analyses, benefit was significant whether women had had a pathologic complete response to neoadjuvant chemotherapy or not. Greatest absolute benefit was seen in those with a pathologic complete response, clinically positive nodes, or pathologically negative nodes.

The 5-year rate of disease-free survival was 74.0% in the entire study population. Here, there was only a trend toward a higher risk of events for women who did not receive radiation therapy.

In multivariate analyses, radiation therapy independently predicted better locoregional recurrence–free survival (hazard ratio, 0.62; P = .038) but not disease-free survival.

When analyses were restricted to women who had undergone mastectomy, radiation therapy was associated with significantly better locoregional recurrence–free survival among those with clinical stage T3/4 disease, pathologically negative nodes, a conversion from clinically positive to pathologically negative nodes, or hormone receptor–negative, HER2-positive disease.

It was associated with poorer disease-free survival for patients who did not achieve a pathologic complete response, had clinical stage T1/2 disease, or were clinically node negative.

Multivariate analysis here again showed that radiation therapy independently predicted better locoregional recurrence–free survival (HR, 0.56; P = .029) but not disease-free survival.

CHICAGO – Women with breast cancer treated with neoadjuvant chemotherapy and surgery are more likely to have a recurrence in the breast, chest wall, or axilla or to die if they don’t receive adjuvant radiation therapy, even if they had a pathologic complete response to the chemotherapy, new data show.

In a meta-analysis of three Gepar trials conducted by the German Breast Group, radiation therapy was associated with a 38% lower multivariate risk of locoregional recurrence or death, investigators reported at the annual meeting of the American Society of Clinical Oncology. Significant benefit was seen regardless of pathologic complete response, although findings across other subgroups were not consistent, possibly due to selection bias or underlying confounders.

“Radiotherapy is an independent prognostic factor for locoregional recurrence–free survival after neoadjuvant chemotherapy in breast cancer. However, the optimal selection criteria remain unclear,” commented first author Dr. David Krug of University Hospital Heidelberg (Germany).

“We are eagerly awaiting the results of prospective studies that are currently recruiting patients,” he added, referring to the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-51 trial and the Radiotherapy After Primary Chemotherapy for Breast Cancer (RAPCHEM) trial.

Findings of this meta-analysis are not practice changing, according to invited discussant Dr. Monica Morrow, chief of the breast service, department of surgery, and the Anne Burnett Windfohr Chair of Clinical Oncology at the Memorial Sloan Kettering Cancer Center in New York. “The Gepar data is not consistent enough across subsets to draw any different conclusions other than we need more data,” she said.

Focusing on the women who underwent mastectomy, she noted that only a small number who had a pathologic complete response did not receive radiation therapy, “so this study unfortunately lacks the power to tell us anything about the ability to eliminate radiation in this group.”

“What we’d really like to know about local control after neoadjuvant therapy is what’s the relative contribution of pretreatment stage and posttreatment stage to the risk of locoregional recurrence, especially in patients who achieve pathologic complete response? And if we try to address that question with this study, the results were a little murky,” Dr. Morrow further noted. For example, patients with higher–T stage primary tumors benefited from postmastectomy radiation, but patients who were clinically node positive did not.

“I think right now, what we have to say is we need to continue to do what we have been doing up until the present time, namely, patients whose presenting stage clearly indicates the need for radiotherapy should receive it, and patients who have lower-stage disease perhaps not,” she concluded, agreeing that the NSABP B-51 trial should help put this issue to rest.

Dr. Krug and his colleagues performed a pooled meta-analysis of data from the GeparTrio, GeparQuattro, and GeparQuinto trials of neoadjuvant chemotherapy, in which guidelines specified when adjuvant radiation therapy should be used. Those guidelines called for whole-breast radiation therapy with a boost after breast-conserving surgery (with omission of the boost in low-risk patients); radiation therapy after mastectomy for patients having more extensive disease before neoadjuvant chemotherapy; and radiation therapy for those with greater involvement of the regional lymphatics.

The meta-analysis was based on a total of 3,370 women. Overall, 94% received radiation therapy (99% of those who had undergone breast-conserving surgery and 85% of those who had undergone mastectomy).

With a median follow-up of 4.2 years, the 5-year rate of locoregional recurrence–free survival was 89.2% in the entire study population, according to Dr. Krug.

Women who did not receive radiation therapy had a significantly elevated risk of such recurrence or death compared with peers who received it. In subgroups analyses, benefit was significant whether women had had a pathologic complete response to neoadjuvant chemotherapy or not. Greatest absolute benefit was seen in those with a pathologic complete response, clinically positive nodes, or pathologically negative nodes.

The 5-year rate of disease-free survival was 74.0% in the entire study population. Here, there was only a trend toward a higher risk of events for women who did not receive radiation therapy.

In multivariate analyses, radiation therapy independently predicted better locoregional recurrence–free survival (hazard ratio, 0.62; P = .038) but not disease-free survival.

When analyses were restricted to women who had undergone mastectomy, radiation therapy was associated with significantly better locoregional recurrence–free survival among those with clinical stage T3/4 disease, pathologically negative nodes, a conversion from clinically positive to pathologically negative nodes, or hormone receptor–negative, HER2-positive disease.

It was associated with poorer disease-free survival for patients who did not achieve a pathologic complete response, had clinical stage T1/2 disease, or were clinically node negative.

Multivariate analysis here again showed that radiation therapy independently predicted better locoregional recurrence–free survival (HR, 0.56; P = .029) but not disease-free survival.

CHICAGO – Women with breast cancer treated with neoadjuvant chemotherapy and surgery are more likely to have a recurrence in the breast, chest wall, or axilla or to die if they don’t receive adjuvant radiation therapy, even if they had a pathologic complete response to the chemotherapy, new data show.

In a meta-analysis of three Gepar trials conducted by the German Breast Group, radiation therapy was associated with a 38% lower multivariate risk of locoregional recurrence or death, investigators reported at the annual meeting of the American Society of Clinical Oncology. Significant benefit was seen regardless of pathologic complete response, although findings across other subgroups were not consistent, possibly due to selection bias or underlying confounders.

“Radiotherapy is an independent prognostic factor for locoregional recurrence–free survival after neoadjuvant chemotherapy in breast cancer. However, the optimal selection criteria remain unclear,” commented first author Dr. David Krug of University Hospital Heidelberg (Germany).

“We are eagerly awaiting the results of prospective studies that are currently recruiting patients,” he added, referring to the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-51 trial and the Radiotherapy After Primary Chemotherapy for Breast Cancer (RAPCHEM) trial.

Findings of this meta-analysis are not practice changing, according to invited discussant Dr. Monica Morrow, chief of the breast service, department of surgery, and the Anne Burnett Windfohr Chair of Clinical Oncology at the Memorial Sloan Kettering Cancer Center in New York. “The Gepar data is not consistent enough across subsets to draw any different conclusions other than we need more data,” she said.

Focusing on the women who underwent mastectomy, she noted that only a small number who had a pathologic complete response did not receive radiation therapy, “so this study unfortunately lacks the power to tell us anything about the ability to eliminate radiation in this group.”

“What we’d really like to know about local control after neoadjuvant therapy is what’s the relative contribution of pretreatment stage and posttreatment stage to the risk of locoregional recurrence, especially in patients who achieve pathologic complete response? And if we try to address that question with this study, the results were a little murky,” Dr. Morrow further noted. For example, patients with higher–T stage primary tumors benefited from postmastectomy radiation, but patients who were clinically node positive did not.

“I think right now, what we have to say is we need to continue to do what we have been doing up until the present time, namely, patients whose presenting stage clearly indicates the need for radiotherapy should receive it, and patients who have lower-stage disease perhaps not,” she concluded, agreeing that the NSABP B-51 trial should help put this issue to rest.

Dr. Krug and his colleagues performed a pooled meta-analysis of data from the GeparTrio, GeparQuattro, and GeparQuinto trials of neoadjuvant chemotherapy, in which guidelines specified when adjuvant radiation therapy should be used. Those guidelines called for whole-breast radiation therapy with a boost after breast-conserving surgery (with omission of the boost in low-risk patients); radiation therapy after mastectomy for patients having more extensive disease before neoadjuvant chemotherapy; and radiation therapy for those with greater involvement of the regional lymphatics.

The meta-analysis was based on a total of 3,370 women. Overall, 94% received radiation therapy (99% of those who had undergone breast-conserving surgery and 85% of those who had undergone mastectomy).

With a median follow-up of 4.2 years, the 5-year rate of locoregional recurrence–free survival was 89.2% in the entire study population, according to Dr. Krug.

Women who did not receive radiation therapy had a significantly elevated risk of such recurrence or death compared with peers who received it. In subgroups analyses, benefit was significant whether women had had a pathologic complete response to neoadjuvant chemotherapy or not. Greatest absolute benefit was seen in those with a pathologic complete response, clinically positive nodes, or pathologically negative nodes.

The 5-year rate of disease-free survival was 74.0% in the entire study population. Here, there was only a trend toward a higher risk of events for women who did not receive radiation therapy.

In multivariate analyses, radiation therapy independently predicted better locoregional recurrence–free survival (hazard ratio, 0.62; P = .038) but not disease-free survival.

When analyses were restricted to women who had undergone mastectomy, radiation therapy was associated with significantly better locoregional recurrence–free survival among those with clinical stage T3/4 disease, pathologically negative nodes, a conversion from clinically positive to pathologically negative nodes, or hormone receptor–negative, HER2-positive disease.

It was associated with poorer disease-free survival for patients who did not achieve a pathologic complete response, had clinical stage T1/2 disease, or were clinically node negative.

Multivariate analysis here again showed that radiation therapy independently predicted better locoregional recurrence–free survival (HR, 0.56; P = .029) but not disease-free survival.

Two newly developed agents, nab-paclitaxel and ixabepilone, both proved inferior to standard once-weekly paclitaxel and caused more toxicities in a phase III trial involving 783 patients with advanced chemotherapy-naive breast cancer, which was reported online June 8 in Journal of Clinical Oncology.

“On the basis of our data, once-per-week paclitaxel should remain the preferred microtubule inhibitor for patients with metastatic breast cancer in the first-line setting,” said Dr. Hope S. Rugo of the University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center and her associates.

Nab-paclitaxel is a novel, solvent-free formulation of paclitaxel in albumin-bound nanoparticles, which precludes the need for premedication to prevent hypersensitivity reactions. Ixabepilone is a semisynthetic analog of epothilone B that binds to the same beta-tubulin site as does paclitaxel.

In phase II studies, both agents appeared to be more potent than paclitaxel and to have similar or superior toxicity profiles. In this trial, patients with metastatic or recurrent breast cancer not amenable to local therapy were randomly assigned to receive nab-paclitaxel (267 participants), ixabepilone (241 participants), or standard paclitaxel (275 participants) as well as bevacizumab; they were followed for a median of 25 months (maximum, 50 months).

The trial was halted early when interim analyses showed that both of the new agents crossed the futility boundary for superiority. The primary endpoint, progression-free survival, was 11 months with paclitaxel. Ixabepilone was clearly inferior, with a median progression-free survival of 7.4 months (HR, 1.59), and nab-paclitaxel trended toward inferiority, with a median progression-free survival of 9.3 months (HR, 1.20). Overall survival rates followed the same pattern. In addition, treatment response rates were lower with both new agents than with paclitaxel, as was palliation of disease-related symptoms.

Both hematologic and nonhematologic toxicities were more severe with the novel drugs than with paclitaxel. These included neutropenia, anemia, sensory neuropathy, fatigue, hypertension, motor neuropathy, pain, and nausea, the investigators said (J. Clin. Oncol. 2015 June 8 [doi:10.1200/JCO.2014.59.5298]).

Unfortunately, before these negative findings were published, the promising results of the phase II studies “led to widespread use of more costly and higher-dose nab-paclitaxel in many clinical practices,” Dr. Rugo and her associates noted.

“Our trial illustrates the importance of adequately powered prospective trials to confirm phase II reports. In addition, these results remind clinicians to be cautious when incorporating new agents, particularly those that are more expensive and potentially more toxic,” they added.

This study was supported by grants from the National Cancer Institute, the Alliance for Clinical Trials in Oncology’s Statistics and Data Center, and the Breast Cancer Research Foundation. Dr. Rugo reported ties to Genomic Health, Plexxikon, MacroGenics, OBI Pharma, Eisai, Pfizer, Novartis, Eli Lilly, GlaxoSmithKline, Genentech, Celsion, Nektar, Merck, Roche, OBI Ontology, and Mylan; her associates reported ties to some of those companies and to Myriad Genetics, Amgen, Celgene, and Verastem.

Two newly developed agents, nab-paclitaxel and ixabepilone, both proved inferior to standard once-weekly paclitaxel and caused more toxicities in a phase III trial involving 783 patients with advanced chemotherapy-naive breast cancer, which was reported online June 8 in Journal of Clinical Oncology.

“On the basis of our data, once-per-week paclitaxel should remain the preferred microtubule inhibitor for patients with metastatic breast cancer in the first-line setting,” said Dr. Hope S. Rugo of the University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center and her associates.

Nab-paclitaxel is a novel, solvent-free formulation of paclitaxel in albumin-bound nanoparticles, which precludes the need for premedication to prevent hypersensitivity reactions. Ixabepilone is a semisynthetic analog of epothilone B that binds to the same beta-tubulin site as does paclitaxel.

In phase II studies, both agents appeared to be more potent than paclitaxel and to have similar or superior toxicity profiles. In this trial, patients with metastatic or recurrent breast cancer not amenable to local therapy were randomly assigned to receive nab-paclitaxel (267 participants), ixabepilone (241 participants), or standard paclitaxel (275 participants) as well as bevacizumab; they were followed for a median of 25 months (maximum, 50 months).

The trial was halted early when interim analyses showed that both of the new agents crossed the futility boundary for superiority. The primary endpoint, progression-free survival, was 11 months with paclitaxel. Ixabepilone was clearly inferior, with a median progression-free survival of 7.4 months (HR, 1.59), and nab-paclitaxel trended toward inferiority, with a median progression-free survival of 9.3 months (HR, 1.20). Overall survival rates followed the same pattern. In addition, treatment response rates were lower with both new agents than with paclitaxel, as was palliation of disease-related symptoms.

Both hematologic and nonhematologic toxicities were more severe with the novel drugs than with paclitaxel. These included neutropenia, anemia, sensory neuropathy, fatigue, hypertension, motor neuropathy, pain, and nausea, the investigators said (J. Clin. Oncol. 2015 June 8 [doi:10.1200/JCO.2014.59.5298]).

Unfortunately, before these negative findings were published, the promising results of the phase II studies “led to widespread use of more costly and higher-dose nab-paclitaxel in many clinical practices,” Dr. Rugo and her associates noted.

“Our trial illustrates the importance of adequately powered prospective trials to confirm phase II reports. In addition, these results remind clinicians to be cautious when incorporating new agents, particularly those that are more expensive and potentially more toxic,” they added.

This study was supported by grants from the National Cancer Institute, the Alliance for Clinical Trials in Oncology’s Statistics and Data Center, and the Breast Cancer Research Foundation. Dr. Rugo reported ties to Genomic Health, Plexxikon, MacroGenics, OBI Pharma, Eisai, Pfizer, Novartis, Eli Lilly, GlaxoSmithKline, Genentech, Celsion, Nektar, Merck, Roche, OBI Ontology, and Mylan; her associates reported ties to some of those companies and to Myriad Genetics, Amgen, Celgene, and Verastem.

Two newly developed agents, nab-paclitaxel and ixabepilone, both proved inferior to standard once-weekly paclitaxel and caused more toxicities in a phase III trial involving 783 patients with advanced chemotherapy-naive breast cancer, which was reported online June 8 in Journal of Clinical Oncology.

“On the basis of our data, once-per-week paclitaxel should remain the preferred microtubule inhibitor for patients with metastatic breast cancer in the first-line setting,” said Dr. Hope S. Rugo of the University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center and her associates.

Nab-paclitaxel is a novel, solvent-free formulation of paclitaxel in albumin-bound nanoparticles, which precludes the need for premedication to prevent hypersensitivity reactions. Ixabepilone is a semisynthetic analog of epothilone B that binds to the same beta-tubulin site as does paclitaxel.

In phase II studies, both agents appeared to be more potent than paclitaxel and to have similar or superior toxicity profiles. In this trial, patients with metastatic or recurrent breast cancer not amenable to local therapy were randomly assigned to receive nab-paclitaxel (267 participants), ixabepilone (241 participants), or standard paclitaxel (275 participants) as well as bevacizumab; they were followed for a median of 25 months (maximum, 50 months).

The trial was halted early when interim analyses showed that both of the new agents crossed the futility boundary for superiority. The primary endpoint, progression-free survival, was 11 months with paclitaxel. Ixabepilone was clearly inferior, with a median progression-free survival of 7.4 months (HR, 1.59), and nab-paclitaxel trended toward inferiority, with a median progression-free survival of 9.3 months (HR, 1.20). Overall survival rates followed the same pattern. In addition, treatment response rates were lower with both new agents than with paclitaxel, as was palliation of disease-related symptoms.

Both hematologic and nonhematologic toxicities were more severe with the novel drugs than with paclitaxel. These included neutropenia, anemia, sensory neuropathy, fatigue, hypertension, motor neuropathy, pain, and nausea, the investigators said (J. Clin. Oncol. 2015 June 8 [doi:10.1200/JCO.2014.59.5298]).

Unfortunately, before these negative findings were published, the promising results of the phase II studies “led to widespread use of more costly and higher-dose nab-paclitaxel in many clinical practices,” Dr. Rugo and her associates noted.

“Our trial illustrates the importance of adequately powered prospective trials to confirm phase II reports. In addition, these results remind clinicians to be cautious when incorporating new agents, particularly those that are more expensive and potentially more toxic,” they added.

This study was supported by grants from the National Cancer Institute, the Alliance for Clinical Trials in Oncology’s Statistics and Data Center, and the Breast Cancer Research Foundation. Dr. Rugo reported ties to Genomic Health, Plexxikon, MacroGenics, OBI Pharma, Eisai, Pfizer, Novartis, Eli Lilly, GlaxoSmithKline, Genentech, Celsion, Nektar, Merck, Roche, OBI Ontology, and Mylan; her associates reported ties to some of those companies and to Myriad Genetics, Amgen, Celgene, and Verastem.

CHICAGO – Dr. William J. Gradishar says bevacizumab may not be dead, T-DM1 is definitely not dead, and the jury is still out on bisphosphonates preventing recurrence, based on presentations at the annual meeting of the American Society of Clinical Oncology.

In a video interview, Dr. Gradishar, the Betsy Bramsen Professor of Breast Oncology at Northwestern University, Chicago, also outlines results presented on newer agents, including the CKD 4/6 inhibitor palbociclib and neratinib, a pan-HER tyrosine kinase inhibitor.

Dr. Gradishar had no financial disclosures related to these studies.

lnikolaides@frontlinemedcom.com

On Twitter @nikolaideslaura

CHICAGO – Dr. William J. Gradishar says bevacizumab may not be dead, T-DM1 is definitely not dead, and the jury is still out on bisphosphonates preventing recurrence, based on presentations at the annual meeting of the American Society of Clinical Oncology.

In a video interview, Dr. Gradishar, the Betsy Bramsen Professor of Breast Oncology at Northwestern University, Chicago, also outlines results presented on newer agents, including the CKD 4/6 inhibitor palbociclib and neratinib, a pan-HER tyrosine kinase inhibitor.

Dr. Gradishar had no financial disclosures related to these studies.

lnikolaides@frontlinemedcom.com

On Twitter @nikolaideslaura

CHICAGO – Dr. William J. Gradishar says bevacizumab may not be dead, T-DM1 is definitely not dead, and the jury is still out on bisphosphonates preventing recurrence, based on presentations at the annual meeting of the American Society of Clinical Oncology.

In a video interview, Dr. Gradishar, the Betsy Bramsen Professor of Breast Oncology at Northwestern University, Chicago, also outlines results presented on newer agents, including the CKD 4/6 inhibitor palbociclib and neratinib, a pan-HER tyrosine kinase inhibitor.

Dr. Gradishar had no financial disclosures related to these studies.

lnikolaides@frontlinemedcom.com

On Twitter @nikolaideslaura