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Pyrotinib bests lapatinib in HER2+ metastatic breast cancer treatment
Among women with HER2-positive metastatic breast cancer enrolled in a phase 2 randomized trial, the pan-ErbB inhibitor pyrotinib plus capecitabine had manageable toxicity and a significantly higher overall response rate (ORR) than lapatinib plus capecitabine, investigators reported.
The pyrotinib/capecitabine combination also led to significantly longer progression-free survival (PFS) versus that of standard lapatinib/capecitabine treatment in these women, who had previously received treatment with taxanes, anthracyclines, and in some cases trastuzumab, the investigators wrote in the Journal of Clinical Oncology.
“To our knowledge, this is the first trial to demonstrate that a novel epidermal growth factor receptor/HER2–targeting tyrosine kinase inhibitor provides ORR and PFS benefits over lapatinib,” wrote Fei Ma, MD, of the National Cancer Center, State Key Laboratory of Molecular Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking, and colleagues.
In the phase 2 study, a total of 128 Chinese women with histologically confirmed relapsed or metastatic breast cancer were randomized to receive the pyrotinib- or lapatinib-containing regimens given in 21-day cycles.
Overall response rates, the primary end point, were 78% (51 of 65 patients) in the pyrotinib arm and 57.1% (36 of 63 patients) in the lapatinib arm (P = .01), Dr. Yu and colleagues reported.
Median PFS was 18.1 months versus 7.0 months in the pyrotinib and lapatinib arms, respectively (P less than .001). A “potential trend” toward improved overall survival was noted in the pyrotinib arm, though the data were premature and not statistically significant at the time of data analysis, according to the investigators.
Altogether, these efficacy results tracked with those of an earlier phase 1 investigation, and currently, a randomized phase 3 study is underway to confirm the findings, reported Dr. Yu and coauthors.
Hand-foot syndrome and diarrhea were the most common grade 3 adverse events seen with pyrotinib. The rate of grade 3 hand-foot syndrome wit pyrotinib was 24.6% versus 20.6% for the lapatinib group, and the rate of grade 3 diarrhea for the two groups was 15.4% and 4.8%, respectively.
Overall, grade 3 or 4 adverse events were seen in 61% of patients receiving pyrotinib, of which 3.1% were grade 4; they were seen in 47.6% of patients receiving lapatinib, of which 3.2% were grade 4.
Diarrhea of grade 3 severity occurred mainly in the first treatment cycle for both the pyrotinib and lapatinib groups, investigators said.
While the protocol for this randomized phase 2 study did not permit diarrhea prophylaxis, the use of prophylactic loperamide is being studied in a phase 3 study of pyrotinib plus trastuzumab and docetaxel in women with HER2-positive metastatic disease and no prior systemic therapy
Investigators said patients are told to interrupt capecitabine if they experience ongoing grade 3 diarrhea or grade 1 or 2 diarrhea with complications such as dehydration, nausea, vomiting, or fever. If the diarrhea persists after 3 days, pyrotinib should then be interrupted, they said.
Similar advice was given for hand-foot syndrome.
“To date, the only method proven to effectively manage hand-foot syndrome is interruption of treatment and, if necessary, dose reduction,” said the investigators, who recommended first interrupting capecitabine and later pyrotinib.
The study was sponsored by Jiangsu Hengrui Medicine and supported by the CAMS Initiative for Innovative Medicine and the National Science and Technology Major Project of the Ministry of Science and Technology in China. The corresponding author of this study, Binghe Xu, MD, PHD, reported institutional research funding from Jiangsu Hengrui Medicine and other disclosures related to AstraZeneca, Pfizer, Roche, and Eisai. Two study coauthors reported employment with Jiangsu Hengrui Medicine.
SOURCE: Ma F et al. J Clin Oncol. 2019 Aug 20. doi: 10.1200/JCO.19.00108.
Among women with HER2-positive metastatic breast cancer enrolled in a phase 2 randomized trial, the pan-ErbB inhibitor pyrotinib plus capecitabine had manageable toxicity and a significantly higher overall response rate (ORR) than lapatinib plus capecitabine, investigators reported.
The pyrotinib/capecitabine combination also led to significantly longer progression-free survival (PFS) versus that of standard lapatinib/capecitabine treatment in these women, who had previously received treatment with taxanes, anthracyclines, and in some cases trastuzumab, the investigators wrote in the Journal of Clinical Oncology.
“To our knowledge, this is the first trial to demonstrate that a novel epidermal growth factor receptor/HER2–targeting tyrosine kinase inhibitor provides ORR and PFS benefits over lapatinib,” wrote Fei Ma, MD, of the National Cancer Center, State Key Laboratory of Molecular Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking, and colleagues.
In the phase 2 study, a total of 128 Chinese women with histologically confirmed relapsed or metastatic breast cancer were randomized to receive the pyrotinib- or lapatinib-containing regimens given in 21-day cycles.
Overall response rates, the primary end point, were 78% (51 of 65 patients) in the pyrotinib arm and 57.1% (36 of 63 patients) in the lapatinib arm (P = .01), Dr. Yu and colleagues reported.
Median PFS was 18.1 months versus 7.0 months in the pyrotinib and lapatinib arms, respectively (P less than .001). A “potential trend” toward improved overall survival was noted in the pyrotinib arm, though the data were premature and not statistically significant at the time of data analysis, according to the investigators.
Altogether, these efficacy results tracked with those of an earlier phase 1 investigation, and currently, a randomized phase 3 study is underway to confirm the findings, reported Dr. Yu and coauthors.
Hand-foot syndrome and diarrhea were the most common grade 3 adverse events seen with pyrotinib. The rate of grade 3 hand-foot syndrome wit pyrotinib was 24.6% versus 20.6% for the lapatinib group, and the rate of grade 3 diarrhea for the two groups was 15.4% and 4.8%, respectively.
Overall, grade 3 or 4 adverse events were seen in 61% of patients receiving pyrotinib, of which 3.1% were grade 4; they were seen in 47.6% of patients receiving lapatinib, of which 3.2% were grade 4.
Diarrhea of grade 3 severity occurred mainly in the first treatment cycle for both the pyrotinib and lapatinib groups, investigators said.
While the protocol for this randomized phase 2 study did not permit diarrhea prophylaxis, the use of prophylactic loperamide is being studied in a phase 3 study of pyrotinib plus trastuzumab and docetaxel in women with HER2-positive metastatic disease and no prior systemic therapy
Investigators said patients are told to interrupt capecitabine if they experience ongoing grade 3 diarrhea or grade 1 or 2 diarrhea with complications such as dehydration, nausea, vomiting, or fever. If the diarrhea persists after 3 days, pyrotinib should then be interrupted, they said.
Similar advice was given for hand-foot syndrome.
“To date, the only method proven to effectively manage hand-foot syndrome is interruption of treatment and, if necessary, dose reduction,” said the investigators, who recommended first interrupting capecitabine and later pyrotinib.
The study was sponsored by Jiangsu Hengrui Medicine and supported by the CAMS Initiative for Innovative Medicine and the National Science and Technology Major Project of the Ministry of Science and Technology in China. The corresponding author of this study, Binghe Xu, MD, PHD, reported institutional research funding from Jiangsu Hengrui Medicine and other disclosures related to AstraZeneca, Pfizer, Roche, and Eisai. Two study coauthors reported employment with Jiangsu Hengrui Medicine.
SOURCE: Ma F et al. J Clin Oncol. 2019 Aug 20. doi: 10.1200/JCO.19.00108.
Among women with HER2-positive metastatic breast cancer enrolled in a phase 2 randomized trial, the pan-ErbB inhibitor pyrotinib plus capecitabine had manageable toxicity and a significantly higher overall response rate (ORR) than lapatinib plus capecitabine, investigators reported.
The pyrotinib/capecitabine combination also led to significantly longer progression-free survival (PFS) versus that of standard lapatinib/capecitabine treatment in these women, who had previously received treatment with taxanes, anthracyclines, and in some cases trastuzumab, the investigators wrote in the Journal of Clinical Oncology.
“To our knowledge, this is the first trial to demonstrate that a novel epidermal growth factor receptor/HER2–targeting tyrosine kinase inhibitor provides ORR and PFS benefits over lapatinib,” wrote Fei Ma, MD, of the National Cancer Center, State Key Laboratory of Molecular Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking, and colleagues.
In the phase 2 study, a total of 128 Chinese women with histologically confirmed relapsed or metastatic breast cancer were randomized to receive the pyrotinib- or lapatinib-containing regimens given in 21-day cycles.
Overall response rates, the primary end point, were 78% (51 of 65 patients) in the pyrotinib arm and 57.1% (36 of 63 patients) in the lapatinib arm (P = .01), Dr. Yu and colleagues reported.
Median PFS was 18.1 months versus 7.0 months in the pyrotinib and lapatinib arms, respectively (P less than .001). A “potential trend” toward improved overall survival was noted in the pyrotinib arm, though the data were premature and not statistically significant at the time of data analysis, according to the investigators.
Altogether, these efficacy results tracked with those of an earlier phase 1 investigation, and currently, a randomized phase 3 study is underway to confirm the findings, reported Dr. Yu and coauthors.
Hand-foot syndrome and diarrhea were the most common grade 3 adverse events seen with pyrotinib. The rate of grade 3 hand-foot syndrome wit pyrotinib was 24.6% versus 20.6% for the lapatinib group, and the rate of grade 3 diarrhea for the two groups was 15.4% and 4.8%, respectively.
Overall, grade 3 or 4 adverse events were seen in 61% of patients receiving pyrotinib, of which 3.1% were grade 4; they were seen in 47.6% of patients receiving lapatinib, of which 3.2% were grade 4.
Diarrhea of grade 3 severity occurred mainly in the first treatment cycle for both the pyrotinib and lapatinib groups, investigators said.
While the protocol for this randomized phase 2 study did not permit diarrhea prophylaxis, the use of prophylactic loperamide is being studied in a phase 3 study of pyrotinib plus trastuzumab and docetaxel in women with HER2-positive metastatic disease and no prior systemic therapy
Investigators said patients are told to interrupt capecitabine if they experience ongoing grade 3 diarrhea or grade 1 or 2 diarrhea with complications such as dehydration, nausea, vomiting, or fever. If the diarrhea persists after 3 days, pyrotinib should then be interrupted, they said.
Similar advice was given for hand-foot syndrome.
“To date, the only method proven to effectively manage hand-foot syndrome is interruption of treatment and, if necessary, dose reduction,” said the investigators, who recommended first interrupting capecitabine and later pyrotinib.
The study was sponsored by Jiangsu Hengrui Medicine and supported by the CAMS Initiative for Innovative Medicine and the National Science and Technology Major Project of the Ministry of Science and Technology in China. The corresponding author of this study, Binghe Xu, MD, PHD, reported institutional research funding from Jiangsu Hengrui Medicine and other disclosures related to AstraZeneca, Pfizer, Roche, and Eisai. Two study coauthors reported employment with Jiangsu Hengrui Medicine.
SOURCE: Ma F et al. J Clin Oncol. 2019 Aug 20. doi: 10.1200/JCO.19.00108.
FROM THE JOURNAL OF CLINICAL ONCOLOGY
USPSTF recommends preventive breast cancer medications only for women at risk
Medication to help prevent breast cancer is not recommended for women without increased risk, but could benefit women at increased risk for the disease, according to an update from the U.S. Preventive Services Task Force.
“Although evidence on the best interval at which to reassess risk and indications for risk-reducing medications is not available, a pragmatic approach would be to repeat risk assessment when there is a significant change in breast cancer risk factors; for instance, when a family member is diagnosed with breast cancer or when there is a new diagnosis of atypical hyperplasia or lobular carcinoma in situ on breast biopsy,” wrote Douglas K. Owens, MD, of Stanford (Calif.) University and members of the task force.
The recommendation applies to asymptomatic women aged 35 years and older, including women with a history of benign breast lesions, but does not apply to women with current or previous breast cancer or ductal carcinoma in situ. The recommendation remains essentially unchanged from the 2013 version, with the addition of aromatase inhibitors (AIs) in the list of options for risk-reducing medications.
In an evidence report accompanying the recommendation, researchers reviewed data from 46 studies including 82 articles and more than 5 million individuals. Overall, among 10 placebo-controlled trials, tamoxifen, raloxifene, and AIs were associated with lower incidence of invasive breast cancer, with risk ratios of 0.69, 0.44, and 0.45, respectively.
However, based on the risk of adverse effects including thromboembolic events, endometrial cancer, and cataracts, the task force determined that the benefits of these medications were no greater than small in women with no risk factors. In addition, 18 risk assessments in 25 studies showed low levels of accuracy in predicting breast cancer risk.
Data from the studies reviewed by the USPSTF showed that the harms of AIs included vasomotor symptoms, GI symptoms, musculoskeletal pain, and potential increased risk of cardiovascular events and fractures. Potential harms of other medications to help prevent breast cancer (tamoxifen and raloxifene) included increased risk for venous thromboembolic events, endometrial cancer, cataracts, and hot flashes.
The findings were limited by several factors including possible publication bias, variation in risk assessment studies, and inability to conduct subgroup analysis, wrote Heidi D. Nelson, MD, of Oregon Health & Sciences University, Portland, and colleagues in the evidence report.
“Although most results are consistent with the 2013 USPSTF review, this update provides additional evidence of the inaccuracy of risk assessment methods,” they noted.
“The USPSTF recommendations, and the accompanying systematic evidence review by Nelson and colleagues rightfully focus on the need to identify women for whom the benefits are likely to outweigh harms, but they also underscore persistent uncertainties about how to accomplish that goal,” wrote Lydia E. Pace, MD, and Nancy L. Keating, MD, both of Brigham and Women’s Hospital in Boston, in an accompanying editorial (JAMA. 2019 Sept 3;322:821-23).
“Identifying safer and more effective preventive medications would help mitigate the low discriminatory accuracy of existing breast cancer risk models,” the editorialists wrote. “Meanwhile, considering risk-reducing medications for women with 5-year risk greater than 3% seems reasonable, as well as for women with atypical hyperplasia and [lobular carcinoma in situ].”
The research was funded by the Agency for Healthcare Research and Quality. Neither the task force researchers nor the editorialists reported relevant financial conflicts.
SOURCEs: Owens DK et al. JAMA. 2019 Sept 3. doi: 10.1001/jama.2019.11885; Nelson HD et al. JAMA. 2019 Sept 3. doi: 10.1001/jama.2019.5780.
Medication to help prevent breast cancer is not recommended for women without increased risk, but could benefit women at increased risk for the disease, according to an update from the U.S. Preventive Services Task Force.
“Although evidence on the best interval at which to reassess risk and indications for risk-reducing medications is not available, a pragmatic approach would be to repeat risk assessment when there is a significant change in breast cancer risk factors; for instance, when a family member is diagnosed with breast cancer or when there is a new diagnosis of atypical hyperplasia or lobular carcinoma in situ on breast biopsy,” wrote Douglas K. Owens, MD, of Stanford (Calif.) University and members of the task force.
The recommendation applies to asymptomatic women aged 35 years and older, including women with a history of benign breast lesions, but does not apply to women with current or previous breast cancer or ductal carcinoma in situ. The recommendation remains essentially unchanged from the 2013 version, with the addition of aromatase inhibitors (AIs) in the list of options for risk-reducing medications.
In an evidence report accompanying the recommendation, researchers reviewed data from 46 studies including 82 articles and more than 5 million individuals. Overall, among 10 placebo-controlled trials, tamoxifen, raloxifene, and AIs were associated with lower incidence of invasive breast cancer, with risk ratios of 0.69, 0.44, and 0.45, respectively.
However, based on the risk of adverse effects including thromboembolic events, endometrial cancer, and cataracts, the task force determined that the benefits of these medications were no greater than small in women with no risk factors. In addition, 18 risk assessments in 25 studies showed low levels of accuracy in predicting breast cancer risk.
Data from the studies reviewed by the USPSTF showed that the harms of AIs included vasomotor symptoms, GI symptoms, musculoskeletal pain, and potential increased risk of cardiovascular events and fractures. Potential harms of other medications to help prevent breast cancer (tamoxifen and raloxifene) included increased risk for venous thromboembolic events, endometrial cancer, cataracts, and hot flashes.
The findings were limited by several factors including possible publication bias, variation in risk assessment studies, and inability to conduct subgroup analysis, wrote Heidi D. Nelson, MD, of Oregon Health & Sciences University, Portland, and colleagues in the evidence report.
“Although most results are consistent with the 2013 USPSTF review, this update provides additional evidence of the inaccuracy of risk assessment methods,” they noted.
“The USPSTF recommendations, and the accompanying systematic evidence review by Nelson and colleagues rightfully focus on the need to identify women for whom the benefits are likely to outweigh harms, but they also underscore persistent uncertainties about how to accomplish that goal,” wrote Lydia E. Pace, MD, and Nancy L. Keating, MD, both of Brigham and Women’s Hospital in Boston, in an accompanying editorial (JAMA. 2019 Sept 3;322:821-23).
“Identifying safer and more effective preventive medications would help mitigate the low discriminatory accuracy of existing breast cancer risk models,” the editorialists wrote. “Meanwhile, considering risk-reducing medications for women with 5-year risk greater than 3% seems reasonable, as well as for women with atypical hyperplasia and [lobular carcinoma in situ].”
The research was funded by the Agency for Healthcare Research and Quality. Neither the task force researchers nor the editorialists reported relevant financial conflicts.
SOURCEs: Owens DK et al. JAMA. 2019 Sept 3. doi: 10.1001/jama.2019.11885; Nelson HD et al. JAMA. 2019 Sept 3. doi: 10.1001/jama.2019.5780.
Medication to help prevent breast cancer is not recommended for women without increased risk, but could benefit women at increased risk for the disease, according to an update from the U.S. Preventive Services Task Force.
“Although evidence on the best interval at which to reassess risk and indications for risk-reducing medications is not available, a pragmatic approach would be to repeat risk assessment when there is a significant change in breast cancer risk factors; for instance, when a family member is diagnosed with breast cancer or when there is a new diagnosis of atypical hyperplasia or lobular carcinoma in situ on breast biopsy,” wrote Douglas K. Owens, MD, of Stanford (Calif.) University and members of the task force.
The recommendation applies to asymptomatic women aged 35 years and older, including women with a history of benign breast lesions, but does not apply to women with current or previous breast cancer or ductal carcinoma in situ. The recommendation remains essentially unchanged from the 2013 version, with the addition of aromatase inhibitors (AIs) in the list of options for risk-reducing medications.
In an evidence report accompanying the recommendation, researchers reviewed data from 46 studies including 82 articles and more than 5 million individuals. Overall, among 10 placebo-controlled trials, tamoxifen, raloxifene, and AIs were associated with lower incidence of invasive breast cancer, with risk ratios of 0.69, 0.44, and 0.45, respectively.
However, based on the risk of adverse effects including thromboembolic events, endometrial cancer, and cataracts, the task force determined that the benefits of these medications were no greater than small in women with no risk factors. In addition, 18 risk assessments in 25 studies showed low levels of accuracy in predicting breast cancer risk.
Data from the studies reviewed by the USPSTF showed that the harms of AIs included vasomotor symptoms, GI symptoms, musculoskeletal pain, and potential increased risk of cardiovascular events and fractures. Potential harms of other medications to help prevent breast cancer (tamoxifen and raloxifene) included increased risk for venous thromboembolic events, endometrial cancer, cataracts, and hot flashes.
The findings were limited by several factors including possible publication bias, variation in risk assessment studies, and inability to conduct subgroup analysis, wrote Heidi D. Nelson, MD, of Oregon Health & Sciences University, Portland, and colleagues in the evidence report.
“Although most results are consistent with the 2013 USPSTF review, this update provides additional evidence of the inaccuracy of risk assessment methods,” they noted.
“The USPSTF recommendations, and the accompanying systematic evidence review by Nelson and colleagues rightfully focus on the need to identify women for whom the benefits are likely to outweigh harms, but they also underscore persistent uncertainties about how to accomplish that goal,” wrote Lydia E. Pace, MD, and Nancy L. Keating, MD, both of Brigham and Women’s Hospital in Boston, in an accompanying editorial (JAMA. 2019 Sept 3;322:821-23).
“Identifying safer and more effective preventive medications would help mitigate the low discriminatory accuracy of existing breast cancer risk models,” the editorialists wrote. “Meanwhile, considering risk-reducing medications for women with 5-year risk greater than 3% seems reasonable, as well as for women with atypical hyperplasia and [lobular carcinoma in situ].”
The research was funded by the Agency for Healthcare Research and Quality. Neither the task force researchers nor the editorialists reported relevant financial conflicts.
SOURCEs: Owens DK et al. JAMA. 2019 Sept 3. doi: 10.1001/jama.2019.11885; Nelson HD et al. JAMA. 2019 Sept 3. doi: 10.1001/jama.2019.5780.
FROM JAMA
Protons safe, effective for breast cancer control
In women with nonmetastatic breast cancer, postoperative regional node irradiation with proton-beam radiation was associated with low rates of toxicity and with disease control rates similar to those reported with conventional photon-based radiation therapy (RT), investigators in a small prospective clinical study reported.
Among 62 survivors of a cohort of 69 women with nonmetastatic breast cancer who required postoperative radiation to the internal mammary nodes (IMN) and for whom conventional radiation was thought to pose excess risks of toxicity, there were no cases of the primary endpoint of grade 3 or greater radiation pneumonitis and no grade 4 toxicities within 3 months of therapy, reported Rachel B. Jimenez, MD, of the Massachusetts General Hospital Cancer Center in Boston and colleagues.
“In our prospective trial of women with locally advanced breast cancer who required treatment of the IMNs, proton beam RT was safe and effective. Future research will provide needed information about the potential long-term normal tissue–sparing benefits of this complex treatment modality compared with conventional radiation,” they wrote in the Journal of Clinical Oncology.
Protons offer the theoretic advantage over photons of minimizing radiation dose to the heart and lungs when treating the breast, chest wall, or regional lymph nodes. Protons, unlike photons, deliver their maximum ionizing energy to tissues immediately before they come to rest, allowing for a more precise dose of radiation to local tissues.
“Multiple dosimetric planning studies that compared proton RT with photon RT have demonstrated superior delivery to targeted areas while sparing more of the heart and lungs. However, prospective clinical data are lacking to support the safety and efficacy of proton RT for breast cancer,” the investigators wrote.
To rectify this, they enrolled adult patients with nonmetastatic breast cancer who required postoperative radiation therapy inclusive of the IMNs and for whom the treating physician determined that either breast reconstruction would prevent adequate target coverage or conventional radiation would deliver 20 Gy or more to 5% or more of the heart and/or the left anterior descending artery (LAD).
A total of 69 patients (median age 45 years) were evaluable for the primary endpoint. In all, 63 of the 70 enrolled patients had left-sided breast cancer, 5 had right-sided breast cancer, and 2 had bilateral breast cancer. The majority of patients (65) had stage II-III disease. All but 2 patients underwent systemic chemotherapy, and 50 underwent immediate reconstruction.
The median of the mean proton radiation dose to the chest wall/breast was 49.7 Gy (relative biological effectiveness) and to the IMN was 48.8 Gy (relative biological effectiveness), indicating comprehensive coverage. The mean heart dose was a median of 0.50 Gy, and the mean dose to the LAD was a median of 1.16 Gy.
After a median follow-up of 55 months, the 5-year rate for locoregional failure among 62 surviving patients was 1.5%
As noted before, there were no cases of grade 3 radiation pneumonitis and no grade 4 toxicities of any type within 3 months of radiation therapy. One patient developed grade 2 radiation pneumonitis 4 months after therapy and was successfully treated with oral corticosteroids, and one developed a severe infection of the bilateral chest wall 4 months after radiation to the left-side chest wall. She was treated with intravenous antibiotics.
There were no significant changes in either echocardiography or cardiac biomarkers after radiotherapy.
The authors noted that the toxicity and disease control rates compared favorably with those of historical data on conventional radiation therapy from two studies published in 2015 (N Engl J Med. 2015;373:307-16; N Engl J Med. 2015;373:317-27).
The study was supported by a grant from the National Institutes of Health. Dr. Jimenez disclosed research funding from Focal Therapeutics.
SOURCE: Jimenez RB et al. J Clin Oncol 2019 Aug 26. doi: 10.1200/JCO.18.02366.
In women with nonmetastatic breast cancer, postoperative regional node irradiation with proton-beam radiation was associated with low rates of toxicity and with disease control rates similar to those reported with conventional photon-based radiation therapy (RT), investigators in a small prospective clinical study reported.
Among 62 survivors of a cohort of 69 women with nonmetastatic breast cancer who required postoperative radiation to the internal mammary nodes (IMN) and for whom conventional radiation was thought to pose excess risks of toxicity, there were no cases of the primary endpoint of grade 3 or greater radiation pneumonitis and no grade 4 toxicities within 3 months of therapy, reported Rachel B. Jimenez, MD, of the Massachusetts General Hospital Cancer Center in Boston and colleagues.
“In our prospective trial of women with locally advanced breast cancer who required treatment of the IMNs, proton beam RT was safe and effective. Future research will provide needed information about the potential long-term normal tissue–sparing benefits of this complex treatment modality compared with conventional radiation,” they wrote in the Journal of Clinical Oncology.
Protons offer the theoretic advantage over photons of minimizing radiation dose to the heart and lungs when treating the breast, chest wall, or regional lymph nodes. Protons, unlike photons, deliver their maximum ionizing energy to tissues immediately before they come to rest, allowing for a more precise dose of radiation to local tissues.
“Multiple dosimetric planning studies that compared proton RT with photon RT have demonstrated superior delivery to targeted areas while sparing more of the heart and lungs. However, prospective clinical data are lacking to support the safety and efficacy of proton RT for breast cancer,” the investigators wrote.
To rectify this, they enrolled adult patients with nonmetastatic breast cancer who required postoperative radiation therapy inclusive of the IMNs and for whom the treating physician determined that either breast reconstruction would prevent adequate target coverage or conventional radiation would deliver 20 Gy or more to 5% or more of the heart and/or the left anterior descending artery (LAD).
A total of 69 patients (median age 45 years) were evaluable for the primary endpoint. In all, 63 of the 70 enrolled patients had left-sided breast cancer, 5 had right-sided breast cancer, and 2 had bilateral breast cancer. The majority of patients (65) had stage II-III disease. All but 2 patients underwent systemic chemotherapy, and 50 underwent immediate reconstruction.
The median of the mean proton radiation dose to the chest wall/breast was 49.7 Gy (relative biological effectiveness) and to the IMN was 48.8 Gy (relative biological effectiveness), indicating comprehensive coverage. The mean heart dose was a median of 0.50 Gy, and the mean dose to the LAD was a median of 1.16 Gy.
After a median follow-up of 55 months, the 5-year rate for locoregional failure among 62 surviving patients was 1.5%
As noted before, there were no cases of grade 3 radiation pneumonitis and no grade 4 toxicities of any type within 3 months of radiation therapy. One patient developed grade 2 radiation pneumonitis 4 months after therapy and was successfully treated with oral corticosteroids, and one developed a severe infection of the bilateral chest wall 4 months after radiation to the left-side chest wall. She was treated with intravenous antibiotics.
There were no significant changes in either echocardiography or cardiac biomarkers after radiotherapy.
The authors noted that the toxicity and disease control rates compared favorably with those of historical data on conventional radiation therapy from two studies published in 2015 (N Engl J Med. 2015;373:307-16; N Engl J Med. 2015;373:317-27).
The study was supported by a grant from the National Institutes of Health. Dr. Jimenez disclosed research funding from Focal Therapeutics.
SOURCE: Jimenez RB et al. J Clin Oncol 2019 Aug 26. doi: 10.1200/JCO.18.02366.
In women with nonmetastatic breast cancer, postoperative regional node irradiation with proton-beam radiation was associated with low rates of toxicity and with disease control rates similar to those reported with conventional photon-based radiation therapy (RT), investigators in a small prospective clinical study reported.
Among 62 survivors of a cohort of 69 women with nonmetastatic breast cancer who required postoperative radiation to the internal mammary nodes (IMN) and for whom conventional radiation was thought to pose excess risks of toxicity, there were no cases of the primary endpoint of grade 3 or greater radiation pneumonitis and no grade 4 toxicities within 3 months of therapy, reported Rachel B. Jimenez, MD, of the Massachusetts General Hospital Cancer Center in Boston and colleagues.
“In our prospective trial of women with locally advanced breast cancer who required treatment of the IMNs, proton beam RT was safe and effective. Future research will provide needed information about the potential long-term normal tissue–sparing benefits of this complex treatment modality compared with conventional radiation,” they wrote in the Journal of Clinical Oncology.
Protons offer the theoretic advantage over photons of minimizing radiation dose to the heart and lungs when treating the breast, chest wall, or regional lymph nodes. Protons, unlike photons, deliver their maximum ionizing energy to tissues immediately before they come to rest, allowing for a more precise dose of radiation to local tissues.
“Multiple dosimetric planning studies that compared proton RT with photon RT have demonstrated superior delivery to targeted areas while sparing more of the heart and lungs. However, prospective clinical data are lacking to support the safety and efficacy of proton RT for breast cancer,” the investigators wrote.
To rectify this, they enrolled adult patients with nonmetastatic breast cancer who required postoperative radiation therapy inclusive of the IMNs and for whom the treating physician determined that either breast reconstruction would prevent adequate target coverage or conventional radiation would deliver 20 Gy or more to 5% or more of the heart and/or the left anterior descending artery (LAD).
A total of 69 patients (median age 45 years) were evaluable for the primary endpoint. In all, 63 of the 70 enrolled patients had left-sided breast cancer, 5 had right-sided breast cancer, and 2 had bilateral breast cancer. The majority of patients (65) had stage II-III disease. All but 2 patients underwent systemic chemotherapy, and 50 underwent immediate reconstruction.
The median of the mean proton radiation dose to the chest wall/breast was 49.7 Gy (relative biological effectiveness) and to the IMN was 48.8 Gy (relative biological effectiveness), indicating comprehensive coverage. The mean heart dose was a median of 0.50 Gy, and the mean dose to the LAD was a median of 1.16 Gy.
After a median follow-up of 55 months, the 5-year rate for locoregional failure among 62 surviving patients was 1.5%
As noted before, there were no cases of grade 3 radiation pneumonitis and no grade 4 toxicities of any type within 3 months of radiation therapy. One patient developed grade 2 radiation pneumonitis 4 months after therapy and was successfully treated with oral corticosteroids, and one developed a severe infection of the bilateral chest wall 4 months after radiation to the left-side chest wall. She was treated with intravenous antibiotics.
There were no significant changes in either echocardiography or cardiac biomarkers after radiotherapy.
The authors noted that the toxicity and disease control rates compared favorably with those of historical data on conventional radiation therapy from two studies published in 2015 (N Engl J Med. 2015;373:307-16; N Engl J Med. 2015;373:317-27).
The study was supported by a grant from the National Institutes of Health. Dr. Jimenez disclosed research funding from Focal Therapeutics.
SOURCE: Jimenez RB et al. J Clin Oncol 2019 Aug 26. doi: 10.1200/JCO.18.02366.
FROM JOURNAL OF CLINICAL ONCOLOGY
Neratinib in combo with T-DM1 shows promise for advanced HER2+ breast cancer
according to results from a phase 1b trial.
“The purpose of this study was to determine the safety and preliminary efficacy of the combination in patients previously treated with trastuzumab plus pertuzumab,” wrote Jame Abraham, MD, of the Cleveland Clinic and colleagues in the Journal of Clinical Oncology.
The open-label, dose-escalation study included 27 women with HER2-positive metastatic breast cancer who had hormone receptor–positive or hormone receptor–negative disease. All participants had demonstrated disease progression, despite prior treatment with combination pertuzumab and trastuzumab, plus a taxane. Among 19 response-evaluable patients, 12 patients (63%) had an objective response. Responses were observed across all neratinib doses, including a complete response in three patients, and partial response in nine patients.
“Deep and more durable responses occurred in patients with cell-free DNA ERBB2 amplification,” Dr. Abraham and associates noted.
“Alterations in the expression of specific HER2 species in ERBB2-amplified cancers, including p95HER2, may have therapeutic implications and require further investigation,” they wrote.
With respect to neratinib dosing, the initial cohort was started at 120 mg daily, which was increased to 240 mg daily in successive cohorts using a 3+3 design. T-DM1 was administered every 3 weeks at 3.6 mg/kg.
After analysis, the researchers proposed a phase 2 dose of neratinib 160 mg once daily and T-DM1 3.6 mg/kg for the combination.
Dose-limiting grade 3 diarrhea was reported in a total of six patients, which was most pronounced in cycle 1. At the phase 2 recommended dose of neratinib, 7 of 10 patients had early-onset diarrhea, which resolved within 24 hours. No grade 4-5 diarrheal toxicities were reported.
Other grade 3-4 adverse events observed were electrolyte abnormalities, thrombocytopenia, nausea, and dehydration.
Phase 2 studies are currently ongoing in order to better characterize the activity of combination T-DM1 and neratinib.
The study was funded by PUMA Biotechnology and the University of Pittsburgh. The authors reported financial affiliations with AstraZeneca, Eisai, Genentech, Guardant Health, Pfizer, Roche, Seattle Genetics, and several others.
SOURCE: Abraham J et al. J Clin Oncol. 2019 Aug 23. doi: 10.1200/JCO.19.00858.
according to results from a phase 1b trial.
“The purpose of this study was to determine the safety and preliminary efficacy of the combination in patients previously treated with trastuzumab plus pertuzumab,” wrote Jame Abraham, MD, of the Cleveland Clinic and colleagues in the Journal of Clinical Oncology.
The open-label, dose-escalation study included 27 women with HER2-positive metastatic breast cancer who had hormone receptor–positive or hormone receptor–negative disease. All participants had demonstrated disease progression, despite prior treatment with combination pertuzumab and trastuzumab, plus a taxane. Among 19 response-evaluable patients, 12 patients (63%) had an objective response. Responses were observed across all neratinib doses, including a complete response in three patients, and partial response in nine patients.
“Deep and more durable responses occurred in patients with cell-free DNA ERBB2 amplification,” Dr. Abraham and associates noted.
“Alterations in the expression of specific HER2 species in ERBB2-amplified cancers, including p95HER2, may have therapeutic implications and require further investigation,” they wrote.
With respect to neratinib dosing, the initial cohort was started at 120 mg daily, which was increased to 240 mg daily in successive cohorts using a 3+3 design. T-DM1 was administered every 3 weeks at 3.6 mg/kg.
After analysis, the researchers proposed a phase 2 dose of neratinib 160 mg once daily and T-DM1 3.6 mg/kg for the combination.
Dose-limiting grade 3 diarrhea was reported in a total of six patients, which was most pronounced in cycle 1. At the phase 2 recommended dose of neratinib, 7 of 10 patients had early-onset diarrhea, which resolved within 24 hours. No grade 4-5 diarrheal toxicities were reported.
Other grade 3-4 adverse events observed were electrolyte abnormalities, thrombocytopenia, nausea, and dehydration.
Phase 2 studies are currently ongoing in order to better characterize the activity of combination T-DM1 and neratinib.
The study was funded by PUMA Biotechnology and the University of Pittsburgh. The authors reported financial affiliations with AstraZeneca, Eisai, Genentech, Guardant Health, Pfizer, Roche, Seattle Genetics, and several others.
SOURCE: Abraham J et al. J Clin Oncol. 2019 Aug 23. doi: 10.1200/JCO.19.00858.
according to results from a phase 1b trial.
“The purpose of this study was to determine the safety and preliminary efficacy of the combination in patients previously treated with trastuzumab plus pertuzumab,” wrote Jame Abraham, MD, of the Cleveland Clinic and colleagues in the Journal of Clinical Oncology.
The open-label, dose-escalation study included 27 women with HER2-positive metastatic breast cancer who had hormone receptor–positive or hormone receptor–negative disease. All participants had demonstrated disease progression, despite prior treatment with combination pertuzumab and trastuzumab, plus a taxane. Among 19 response-evaluable patients, 12 patients (63%) had an objective response. Responses were observed across all neratinib doses, including a complete response in three patients, and partial response in nine patients.
“Deep and more durable responses occurred in patients with cell-free DNA ERBB2 amplification,” Dr. Abraham and associates noted.
“Alterations in the expression of specific HER2 species in ERBB2-amplified cancers, including p95HER2, may have therapeutic implications and require further investigation,” they wrote.
With respect to neratinib dosing, the initial cohort was started at 120 mg daily, which was increased to 240 mg daily in successive cohorts using a 3+3 design. T-DM1 was administered every 3 weeks at 3.6 mg/kg.
After analysis, the researchers proposed a phase 2 dose of neratinib 160 mg once daily and T-DM1 3.6 mg/kg for the combination.
Dose-limiting grade 3 diarrhea was reported in a total of six patients, which was most pronounced in cycle 1. At the phase 2 recommended dose of neratinib, 7 of 10 patients had early-onset diarrhea, which resolved within 24 hours. No grade 4-5 diarrheal toxicities were reported.
Other grade 3-4 adverse events observed were electrolyte abnormalities, thrombocytopenia, nausea, and dehydration.
Phase 2 studies are currently ongoing in order to better characterize the activity of combination T-DM1 and neratinib.
The study was funded by PUMA Biotechnology and the University of Pittsburgh. The authors reported financial affiliations with AstraZeneca, Eisai, Genentech, Guardant Health, Pfizer, Roche, Seattle Genetics, and several others.
SOURCE: Abraham J et al. J Clin Oncol. 2019 Aug 23. doi: 10.1200/JCO.19.00858.
REPORTING FROM THE JOURNAL OF CLINICAL ONCOLOGY
Oncologists agree with AI treatment decisions about half the time
When it comes to treatment recommendations for high-risk breast cancer, oncologists agree with a leading artificial intelligence platform about half the time, according to investigators.
In the first study of its kind, involving 10 Chinese oncologists, recommendation concordance with the Watson for Oncology treatment advisory tool (WfO) was generally lower for hormone receptor–positive and metastatic cancers than hormone receptor–negative and nonmetastatic cases, reported Fengrui Xu, MD, of the Academy of Military Medical Sciences in Beijing, and colleagues. Refinement could enable broad use of Watson, not to dictate treatment decisions, but instead to propose alternate treatment approaches and offer point-of-care access to relevant evidence.
“[WfO] is an example of a quantitative oncology clinical decision support that leverages the clinical expertise of oncologists at Memorial Sloan Kettering Cancer Center [MSKCC],” the investigators wrote in JCO Clinical Cancer Informatics. The platform uses machine-learning software to interpret patient scenarios in light from MSKCC training cases, MSKCC treatment guidelines, and more than 300 medical textbooks and journals.
To compare WfO with real-world decision makers, the investigators recruited three chief physicians, four attending physicians, and three fellows to provide treatment recommendations for 1,977 patients with complex breast cancer who were treated at 10 hospitals in China. Participating physicians shared the workload; each evaluated an average of 198 different cases.
On average, oncologists and WfO made the same treatment recommendations 56% of the time. Out of the different types of physicians, fellows were most likely to agree with WfO, based on a 68% concordance rate, compared with 54% for chief physicians and 49% for attending physicians. Including all physicians, concordance was lowest for hormone receptor–positive/HER2-positive disease (48%) and highest for triple-negative cases (71%). Adjuvant and metastatic therapies were also evaluated, with high concordance for adjuvant endocrine (78%) and targeted therapy (100%), compared with moderate concordance for first- (52%) and second-line metastatic therapy (50%). The investigators described concordance results as generally “modest;” however, they noted that such levels are promising.
“This degree of concordance is encouraging because therapeutic decisions in these cases are often difficult as a result of the current limits of medical knowledge for treating complex breast cancers and the presence of local contextual factors that affect physician treatment choices,” the investigators wrote. “It is important to note that nonconcordance does not imply that one treatment is correct for a given patient and another is not, nor does it necessarily diminish the potential value of a decision support system that provides access to supporting evidence and insight into its reasoning process.”
The study was funded by Zefei Jiang. The investigators reported affiliations with IBM Watson Health, Pharmaceutical Manufacturer Institution, Merck, and others.
SOURCE: Xu F et al. JCO Clin Cancer Inform. 2019 Aug 16. doi: 10.1200/CCI.18.00159.
When it comes to treatment recommendations for high-risk breast cancer, oncologists agree with a leading artificial intelligence platform about half the time, according to investigators.
In the first study of its kind, involving 10 Chinese oncologists, recommendation concordance with the Watson for Oncology treatment advisory tool (WfO) was generally lower for hormone receptor–positive and metastatic cancers than hormone receptor–negative and nonmetastatic cases, reported Fengrui Xu, MD, of the Academy of Military Medical Sciences in Beijing, and colleagues. Refinement could enable broad use of Watson, not to dictate treatment decisions, but instead to propose alternate treatment approaches and offer point-of-care access to relevant evidence.
“[WfO] is an example of a quantitative oncology clinical decision support that leverages the clinical expertise of oncologists at Memorial Sloan Kettering Cancer Center [MSKCC],” the investigators wrote in JCO Clinical Cancer Informatics. The platform uses machine-learning software to interpret patient scenarios in light from MSKCC training cases, MSKCC treatment guidelines, and more than 300 medical textbooks and journals.
To compare WfO with real-world decision makers, the investigators recruited three chief physicians, four attending physicians, and three fellows to provide treatment recommendations for 1,977 patients with complex breast cancer who were treated at 10 hospitals in China. Participating physicians shared the workload; each evaluated an average of 198 different cases.
On average, oncologists and WfO made the same treatment recommendations 56% of the time. Out of the different types of physicians, fellows were most likely to agree with WfO, based on a 68% concordance rate, compared with 54% for chief physicians and 49% for attending physicians. Including all physicians, concordance was lowest for hormone receptor–positive/HER2-positive disease (48%) and highest for triple-negative cases (71%). Adjuvant and metastatic therapies were also evaluated, with high concordance for adjuvant endocrine (78%) and targeted therapy (100%), compared with moderate concordance for first- (52%) and second-line metastatic therapy (50%). The investigators described concordance results as generally “modest;” however, they noted that such levels are promising.
“This degree of concordance is encouraging because therapeutic decisions in these cases are often difficult as a result of the current limits of medical knowledge for treating complex breast cancers and the presence of local contextual factors that affect physician treatment choices,” the investigators wrote. “It is important to note that nonconcordance does not imply that one treatment is correct for a given patient and another is not, nor does it necessarily diminish the potential value of a decision support system that provides access to supporting evidence and insight into its reasoning process.”
The study was funded by Zefei Jiang. The investigators reported affiliations with IBM Watson Health, Pharmaceutical Manufacturer Institution, Merck, and others.
SOURCE: Xu F et al. JCO Clin Cancer Inform. 2019 Aug 16. doi: 10.1200/CCI.18.00159.
When it comes to treatment recommendations for high-risk breast cancer, oncologists agree with a leading artificial intelligence platform about half the time, according to investigators.
In the first study of its kind, involving 10 Chinese oncologists, recommendation concordance with the Watson for Oncology treatment advisory tool (WfO) was generally lower for hormone receptor–positive and metastatic cancers than hormone receptor–negative and nonmetastatic cases, reported Fengrui Xu, MD, of the Academy of Military Medical Sciences in Beijing, and colleagues. Refinement could enable broad use of Watson, not to dictate treatment decisions, but instead to propose alternate treatment approaches and offer point-of-care access to relevant evidence.
“[WfO] is an example of a quantitative oncology clinical decision support that leverages the clinical expertise of oncologists at Memorial Sloan Kettering Cancer Center [MSKCC],” the investigators wrote in JCO Clinical Cancer Informatics. The platform uses machine-learning software to interpret patient scenarios in light from MSKCC training cases, MSKCC treatment guidelines, and more than 300 medical textbooks and journals.
To compare WfO with real-world decision makers, the investigators recruited three chief physicians, four attending physicians, and three fellows to provide treatment recommendations for 1,977 patients with complex breast cancer who were treated at 10 hospitals in China. Participating physicians shared the workload; each evaluated an average of 198 different cases.
On average, oncologists and WfO made the same treatment recommendations 56% of the time. Out of the different types of physicians, fellows were most likely to agree with WfO, based on a 68% concordance rate, compared with 54% for chief physicians and 49% for attending physicians. Including all physicians, concordance was lowest for hormone receptor–positive/HER2-positive disease (48%) and highest for triple-negative cases (71%). Adjuvant and metastatic therapies were also evaluated, with high concordance for adjuvant endocrine (78%) and targeted therapy (100%), compared with moderate concordance for first- (52%) and second-line metastatic therapy (50%). The investigators described concordance results as generally “modest;” however, they noted that such levels are promising.
“This degree of concordance is encouraging because therapeutic decisions in these cases are often difficult as a result of the current limits of medical knowledge for treating complex breast cancers and the presence of local contextual factors that affect physician treatment choices,” the investigators wrote. “It is important to note that nonconcordance does not imply that one treatment is correct for a given patient and another is not, nor does it necessarily diminish the potential value of a decision support system that provides access to supporting evidence and insight into its reasoning process.”
The study was funded by Zefei Jiang. The investigators reported affiliations with IBM Watson Health, Pharmaceutical Manufacturer Institution, Merck, and others.
SOURCE: Xu F et al. JCO Clin Cancer Inform. 2019 Aug 16. doi: 10.1200/CCI.18.00159.
FROM JCO CLINICAL CANCER INFORMATICS
Cancer survivors face more age-related deficits
Long-term survivors of cancer have more age-related functional deficits than do those who have not experienced cancer, and these deficits – as well as their cancer history – are both associated with a higher risk of all-cause mortality, a study has found.
A paper published in Cancer reported the outcomes of a population-based cohort study involving 1,723 female cancer survivors and 11,145 cancer-free women enrolled in the Iowa Women’s Health Study, who were followed for 10 years.
The analysis revealed that women with a history of cancer had significantly more deficits on a geriatric assessment compared with their age-matched controls without a history of cancer. While 66% of women without a cancer history had one or more deficits, 70% of those with a history had at least one age-related deficit, and they were significantly more likely to have two or more deficits.
Cancer survivors were significantly more likely to have two or more physical function limitations than were those without a history of cancer (42.4% vs. 36.9%, P less than .0001), to have two or more comorbidities (41.3% vs. 38.2%, P = .02) and to have poor general health (23.3% vs. 17.4%, P less than .0001). They were also significantly less likely to be underweight.
The study found that both cancer history and age-related functional deficits were predictors of mortality, even after adjustment for confounders such as chronological age, smoking, and physical activity levels. The highest mortality risk was seen in cancer survivors with two or more age-related health deficits, who had a twofold greater mortality risk compared with the noncancer controls with fewer than two health deficits.
Even individuals with a history of cancer but without any health deficits still had a 1.3-1.4-fold increased risk of mortality compared with individuals without a history of cancer and without health deficits.
“These results confirm the increased risk of mortality associated with GA domain deficits and extend the research by demonstrating that a cancer history is associated with an older functional age compared with aged-matched cancer-free individuals,” wrote Cindy K. Blair, PhD, of the department of internal medicine at the University of New Mexico, Albuquerque, and coauthors.
They noted that the study included very long-term cancer survivors who had survived for an average of 11 years before they underwent the geriatric assessment and were then followed for 10 years after that point.
“Further research is needed to identify older cancer survivors who are at risk of accelerated aging,” the authors wrote. “Interventions that target physical function, comorbidity, nutritional status, and general health are greatly needed to improve or maintain the quality of survivorship in older cancer survivors.”
The National Cancer Institute, the University of Minnesota Cancer Center, and the University of New Mexico Comprehensive Cancer Center supported the study. Two authors declared grants from the National Institutes of Health related to the study.
SOURCE: Blair C et al. Cancer 2019, Aug 16. doi: 10.1002/cncr.32449.
Long-term survivors of cancer have more age-related functional deficits than do those who have not experienced cancer, and these deficits – as well as their cancer history – are both associated with a higher risk of all-cause mortality, a study has found.
A paper published in Cancer reported the outcomes of a population-based cohort study involving 1,723 female cancer survivors and 11,145 cancer-free women enrolled in the Iowa Women’s Health Study, who were followed for 10 years.
The analysis revealed that women with a history of cancer had significantly more deficits on a geriatric assessment compared with their age-matched controls without a history of cancer. While 66% of women without a cancer history had one or more deficits, 70% of those with a history had at least one age-related deficit, and they were significantly more likely to have two or more deficits.
Cancer survivors were significantly more likely to have two or more physical function limitations than were those without a history of cancer (42.4% vs. 36.9%, P less than .0001), to have two or more comorbidities (41.3% vs. 38.2%, P = .02) and to have poor general health (23.3% vs. 17.4%, P less than .0001). They were also significantly less likely to be underweight.
The study found that both cancer history and age-related functional deficits were predictors of mortality, even after adjustment for confounders such as chronological age, smoking, and physical activity levels. The highest mortality risk was seen in cancer survivors with two or more age-related health deficits, who had a twofold greater mortality risk compared with the noncancer controls with fewer than two health deficits.
Even individuals with a history of cancer but without any health deficits still had a 1.3-1.4-fold increased risk of mortality compared with individuals without a history of cancer and without health deficits.
“These results confirm the increased risk of mortality associated with GA domain deficits and extend the research by demonstrating that a cancer history is associated with an older functional age compared with aged-matched cancer-free individuals,” wrote Cindy K. Blair, PhD, of the department of internal medicine at the University of New Mexico, Albuquerque, and coauthors.
They noted that the study included very long-term cancer survivors who had survived for an average of 11 years before they underwent the geriatric assessment and were then followed for 10 years after that point.
“Further research is needed to identify older cancer survivors who are at risk of accelerated aging,” the authors wrote. “Interventions that target physical function, comorbidity, nutritional status, and general health are greatly needed to improve or maintain the quality of survivorship in older cancer survivors.”
The National Cancer Institute, the University of Minnesota Cancer Center, and the University of New Mexico Comprehensive Cancer Center supported the study. Two authors declared grants from the National Institutes of Health related to the study.
SOURCE: Blair C et al. Cancer 2019, Aug 16. doi: 10.1002/cncr.32449.
Long-term survivors of cancer have more age-related functional deficits than do those who have not experienced cancer, and these deficits – as well as their cancer history – are both associated with a higher risk of all-cause mortality, a study has found.
A paper published in Cancer reported the outcomes of a population-based cohort study involving 1,723 female cancer survivors and 11,145 cancer-free women enrolled in the Iowa Women’s Health Study, who were followed for 10 years.
The analysis revealed that women with a history of cancer had significantly more deficits on a geriatric assessment compared with their age-matched controls without a history of cancer. While 66% of women without a cancer history had one or more deficits, 70% of those with a history had at least one age-related deficit, and they were significantly more likely to have two or more deficits.
Cancer survivors were significantly more likely to have two or more physical function limitations than were those without a history of cancer (42.4% vs. 36.9%, P less than .0001), to have two or more comorbidities (41.3% vs. 38.2%, P = .02) and to have poor general health (23.3% vs. 17.4%, P less than .0001). They were also significantly less likely to be underweight.
The study found that both cancer history and age-related functional deficits were predictors of mortality, even after adjustment for confounders such as chronological age, smoking, and physical activity levels. The highest mortality risk was seen in cancer survivors with two or more age-related health deficits, who had a twofold greater mortality risk compared with the noncancer controls with fewer than two health deficits.
Even individuals with a history of cancer but without any health deficits still had a 1.3-1.4-fold increased risk of mortality compared with individuals without a history of cancer and without health deficits.
“These results confirm the increased risk of mortality associated with GA domain deficits and extend the research by demonstrating that a cancer history is associated with an older functional age compared with aged-matched cancer-free individuals,” wrote Cindy K. Blair, PhD, of the department of internal medicine at the University of New Mexico, Albuquerque, and coauthors.
They noted that the study included very long-term cancer survivors who had survived for an average of 11 years before they underwent the geriatric assessment and were then followed for 10 years after that point.
“Further research is needed to identify older cancer survivors who are at risk of accelerated aging,” the authors wrote. “Interventions that target physical function, comorbidity, nutritional status, and general health are greatly needed to improve or maintain the quality of survivorship in older cancer survivors.”
The National Cancer Institute, the University of Minnesota Cancer Center, and the University of New Mexico Comprehensive Cancer Center supported the study. Two authors declared grants from the National Institutes of Health related to the study.
SOURCE: Blair C et al. Cancer 2019, Aug 16. doi: 10.1002/cncr.32449.
FROM CANCER
Diet, exercise don’t improve breast cancer-related lymphedema
Neither weight-loss nor home-based exercise programs improved outcomes for women with breast cancer–related lymphedema, investigators found.
Among 351 overweight breast cancer survivors with breast cancer–related lymphedema (BCRL), there were no significant differences at 1 year of follow-up in the percentage difference between limb volumes from baseline, regardless of whether patients had been randomly assigned to a home-based exercise program, weight-loss program, combined interventions, or to a facility-based lymphedema care–only program, reported Kathryn H. Schmitz, PhD, MPH, from Penn State University, Hershey, and colleagues.
“Our findings are contradictory to our own clinical experience, as we have received reports from patients with BCRL who have noted improvements in their lymphedema symptoms after weight loss. Possible explanations for this mismatch of clinical experience and empirical evidence include alterations in aspects of lymphedema, such as tissue composition, that remain challenging to measure with high reliability and validity,” they wrote in JAMA Oncology.
The findings suggest that breast cancer survivors with lymphedema may benefit more from facility-based exercise than home-based lymphedema care, the investigators wrote.
In the randomized Women in Steady Exercise Research (WISER) Survivor trial, the investigators enrolled 351 overweight breast cancer survivors with lymphedema and randomly assigned them to a 52-week home-based exercise program consisting of strength and resistance training twice per week and 180 minutes per week of walking (87 patients), a weight-loss program consisting of 20 weeks of meal replacement and 1 year of lifestyle-modification counseling (87 patients), a combination of the two programs (87 patients), or a facility-based lymphedema care program only (90 patients, control group).
The primary endpoint was originally intended to be lymphedema clinical events such as incident flare-ups or cellulitis, but was changed to the percentage of interlimb difference (that is, between the affected and unaffected limb) because of a reduction in funding that led to a reduction in the sample size.
There were no significant between-group differences at either baseline or 12 months in either the percentage of interlimb differences or in absolute differences, the investigators found.
Women assigned to the diet and exercise intervention lost significantly more weight than controls (P less than .001), but saw significant improvements in fitness only in the maximum amount of weight they could lift (P = .01).
“Multiple national organizations currently advise overweight women to achieve and maintain a healthy weight to improve the outcomes of previously diagnosed BCRL. The empirical evidence base, including data from the present study, does not support the assertion that weight loss as an intervention improves the hallmark measure of BCRL severity, percentage of interlimb difference,” Dr. Schmitz and colleagues wrote.
They acknowledged that BCRL is a long-term condition and that the 1-year follow-up period may have been too short to observe lymphedema exacerbation or related clinical events; therefore, the results may not apply to women with severe lymphedema, such as those with interlimb differences of greater than 30%.
The study was supported by various National Institutes of Health grants. Compression garments were supplied by BSN Medical. Dr. Schmitz reported receiving grants from the National Cancer Institute and nonfinancial support from BSN Medical during the conduct of the study, personal fees from Klose Training outside the submitted work, and a licensed patent for a Strength After Breast Cancer course.
SOURCE: Schmitz KH et al. JAMA Oncol. 2019 Aug 15. doi: 10.1001/jamaoncol.2019.2109..
Neither weight-loss nor home-based exercise programs improved outcomes for women with breast cancer–related lymphedema, investigators found.
Among 351 overweight breast cancer survivors with breast cancer–related lymphedema (BCRL), there were no significant differences at 1 year of follow-up in the percentage difference between limb volumes from baseline, regardless of whether patients had been randomly assigned to a home-based exercise program, weight-loss program, combined interventions, or to a facility-based lymphedema care–only program, reported Kathryn H. Schmitz, PhD, MPH, from Penn State University, Hershey, and colleagues.
“Our findings are contradictory to our own clinical experience, as we have received reports from patients with BCRL who have noted improvements in their lymphedema symptoms after weight loss. Possible explanations for this mismatch of clinical experience and empirical evidence include alterations in aspects of lymphedema, such as tissue composition, that remain challenging to measure with high reliability and validity,” they wrote in JAMA Oncology.
The findings suggest that breast cancer survivors with lymphedema may benefit more from facility-based exercise than home-based lymphedema care, the investigators wrote.
In the randomized Women in Steady Exercise Research (WISER) Survivor trial, the investigators enrolled 351 overweight breast cancer survivors with lymphedema and randomly assigned them to a 52-week home-based exercise program consisting of strength and resistance training twice per week and 180 minutes per week of walking (87 patients), a weight-loss program consisting of 20 weeks of meal replacement and 1 year of lifestyle-modification counseling (87 patients), a combination of the two programs (87 patients), or a facility-based lymphedema care program only (90 patients, control group).
The primary endpoint was originally intended to be lymphedema clinical events such as incident flare-ups or cellulitis, but was changed to the percentage of interlimb difference (that is, between the affected and unaffected limb) because of a reduction in funding that led to a reduction in the sample size.
There were no significant between-group differences at either baseline or 12 months in either the percentage of interlimb differences or in absolute differences, the investigators found.
Women assigned to the diet and exercise intervention lost significantly more weight than controls (P less than .001), but saw significant improvements in fitness only in the maximum amount of weight they could lift (P = .01).
“Multiple national organizations currently advise overweight women to achieve and maintain a healthy weight to improve the outcomes of previously diagnosed BCRL. The empirical evidence base, including data from the present study, does not support the assertion that weight loss as an intervention improves the hallmark measure of BCRL severity, percentage of interlimb difference,” Dr. Schmitz and colleagues wrote.
They acknowledged that BCRL is a long-term condition and that the 1-year follow-up period may have been too short to observe lymphedema exacerbation or related clinical events; therefore, the results may not apply to women with severe lymphedema, such as those with interlimb differences of greater than 30%.
The study was supported by various National Institutes of Health grants. Compression garments were supplied by BSN Medical. Dr. Schmitz reported receiving grants from the National Cancer Institute and nonfinancial support from BSN Medical during the conduct of the study, personal fees from Klose Training outside the submitted work, and a licensed patent for a Strength After Breast Cancer course.
SOURCE: Schmitz KH et al. JAMA Oncol. 2019 Aug 15. doi: 10.1001/jamaoncol.2019.2109..
Neither weight-loss nor home-based exercise programs improved outcomes for women with breast cancer–related lymphedema, investigators found.
Among 351 overweight breast cancer survivors with breast cancer–related lymphedema (BCRL), there were no significant differences at 1 year of follow-up in the percentage difference between limb volumes from baseline, regardless of whether patients had been randomly assigned to a home-based exercise program, weight-loss program, combined interventions, or to a facility-based lymphedema care–only program, reported Kathryn H. Schmitz, PhD, MPH, from Penn State University, Hershey, and colleagues.
“Our findings are contradictory to our own clinical experience, as we have received reports from patients with BCRL who have noted improvements in their lymphedema symptoms after weight loss. Possible explanations for this mismatch of clinical experience and empirical evidence include alterations in aspects of lymphedema, such as tissue composition, that remain challenging to measure with high reliability and validity,” they wrote in JAMA Oncology.
The findings suggest that breast cancer survivors with lymphedema may benefit more from facility-based exercise than home-based lymphedema care, the investigators wrote.
In the randomized Women in Steady Exercise Research (WISER) Survivor trial, the investigators enrolled 351 overweight breast cancer survivors with lymphedema and randomly assigned them to a 52-week home-based exercise program consisting of strength and resistance training twice per week and 180 minutes per week of walking (87 patients), a weight-loss program consisting of 20 weeks of meal replacement and 1 year of lifestyle-modification counseling (87 patients), a combination of the two programs (87 patients), or a facility-based lymphedema care program only (90 patients, control group).
The primary endpoint was originally intended to be lymphedema clinical events such as incident flare-ups or cellulitis, but was changed to the percentage of interlimb difference (that is, between the affected and unaffected limb) because of a reduction in funding that led to a reduction in the sample size.
There were no significant between-group differences at either baseline or 12 months in either the percentage of interlimb differences or in absolute differences, the investigators found.
Women assigned to the diet and exercise intervention lost significantly more weight than controls (P less than .001), but saw significant improvements in fitness only in the maximum amount of weight they could lift (P = .01).
“Multiple national organizations currently advise overweight women to achieve and maintain a healthy weight to improve the outcomes of previously diagnosed BCRL. The empirical evidence base, including data from the present study, does not support the assertion that weight loss as an intervention improves the hallmark measure of BCRL severity, percentage of interlimb difference,” Dr. Schmitz and colleagues wrote.
They acknowledged that BCRL is a long-term condition and that the 1-year follow-up period may have been too short to observe lymphedema exacerbation or related clinical events; therefore, the results may not apply to women with severe lymphedema, such as those with interlimb differences of greater than 30%.
The study was supported by various National Institutes of Health grants. Compression garments were supplied by BSN Medical. Dr. Schmitz reported receiving grants from the National Cancer Institute and nonfinancial support from BSN Medical during the conduct of the study, personal fees from Klose Training outside the submitted work, and a licensed patent for a Strength After Breast Cancer course.
SOURCE: Schmitz KH et al. JAMA Oncol. 2019 Aug 15. doi: 10.1001/jamaoncol.2019.2109..
FROM JAMA ONCOLOGY
Recurrence score may help predict chemotherapy benefit in grade 3 breast cancers
For patients with grade 3 breast cancer, recurrence score testing may have significant clinical value in determining which patients are likely to benefit from chemotherapy, according to investigators who recently reported results of a large, national cohort study.
Among patients with pN0/1 grade 3 invasive breast cancers, about one-third had a low recurrence score, which was associated with no early benefit from the addition of chemotherapy, wrote senior study author Jane E. Brock, MBBS, PhD, of Harvard Medical School, Boston, and coauthors.
Incorporating recurrence score testing into clinical decision making may help “tailor treatment recommendations” for patients with grade 3 invasive breast cancers, Dr. Brock and coauthors reported in JCO Precision Oncology.
“To our knowledge, these findings represent the largest analysis to date of the potential impact of recurrence score on the outcomes and management of grade 3 tumors, and suggest that the assumption that all pT1c/2 pN0/1, [estrogen receptor–positive] histopathologic grade 3 tumors are high risk and will consequently benefit from adjuvant chemotherapy may be unmerited,” the Dr. Brock and coauthors wrote in the report.
These findings “fill a gap” as the final results of the RxPONDER trial are awaited, according to investigators. Specifically, RxPONDER is designed to evaluate the potential benefit of adjuvant chemotherapy in pN0/1 patients with intermediate range recurrence scores.
Moreover, the findings complement the reported results of the TAILORx trial, which showed that chemotherapy does not provide a benefit in most low and intermediate recurrence score tumors, which suggests some patients may safely omit chemotherapy without affecting outcomes, the investigators added.
The present analysis included a total of 30,864 grade 3 breast cancers from the National Cancer Database, which represents more than 70% of new diagnoses in the United States, according to investigators.
Testing using the 21-gene Oncotype DX Breast Recurrence Score increased over time for pN0 cancers, from 53% in 2010 to 72% in 2015, investigators found; likewise, for pN1 cancers, testing increased from 16% to 36% over that time period. They also found that, overall, 30% of pN0 and 27.1% of pN1 cancers had a low recurrence score.
Adjuvant chemotherapy was not associated with any additional benefit in patients with low recurrence scores, according to the analysis.
For patients with intermediate recurrence scores, chemotherapy was linked to improved survival in univariable analyses, but following adjustment for clinical and pathologic characteristics, intermediate scores were not predictive of a significant overall survival benefit, investigators found.
By contrast, chemotherapy was associated with additional benefit in patients with high recurrence scores in both univariable and multivariable analyses.
For patients with pN0 grade 3 disease and high recurrence score, chemotherapy was linked to significantly improved overall survival, compared with that of patients who received no chemotherapy (hazard ratio, 0.63; 95% confidence interval, 0.43-0.90; P = .01), while a similar survival benefit was reported among patients with pN1 disease and high recurrence scores (HR, 0.24; 95% CI, 0.13-0.47; P less than .001).
These results suggest that recurrence score may aid in determining the anticipated benefit of chemotherapy in this heterogeneous cohort of patients, investigators wrote.
“Furthermore, our findings show significant variability in national patterns of recurrence testing and chemotherapy use for grade 3 disease, which suggests opportunities for more comprehensive national guidelines for recurrence score testing in high-grade tumors,” they concluded.
Dr. Brock reported no potential conflicts of interest. Coauthors provided disclosures related to AstraZeneca, Blade Therapeutics, Eisai, EMD Serono, Galena Biopharma, Genentech, Genomic Health, Novartis, Novartis Institutes for BioMedical Research, Peregrine, Puma Biotechnology, resTORbio, Roche, and others.
SOURCE: Brock JE et al. JCO Precis Oncol. 2019 Aug 14. doi: 10.1200/PO.19.00029.
For patients with grade 3 breast cancer, recurrence score testing may have significant clinical value in determining which patients are likely to benefit from chemotherapy, according to investigators who recently reported results of a large, national cohort study.
Among patients with pN0/1 grade 3 invasive breast cancers, about one-third had a low recurrence score, which was associated with no early benefit from the addition of chemotherapy, wrote senior study author Jane E. Brock, MBBS, PhD, of Harvard Medical School, Boston, and coauthors.
Incorporating recurrence score testing into clinical decision making may help “tailor treatment recommendations” for patients with grade 3 invasive breast cancers, Dr. Brock and coauthors reported in JCO Precision Oncology.
“To our knowledge, these findings represent the largest analysis to date of the potential impact of recurrence score on the outcomes and management of grade 3 tumors, and suggest that the assumption that all pT1c/2 pN0/1, [estrogen receptor–positive] histopathologic grade 3 tumors are high risk and will consequently benefit from adjuvant chemotherapy may be unmerited,” the Dr. Brock and coauthors wrote in the report.
These findings “fill a gap” as the final results of the RxPONDER trial are awaited, according to investigators. Specifically, RxPONDER is designed to evaluate the potential benefit of adjuvant chemotherapy in pN0/1 patients with intermediate range recurrence scores.
Moreover, the findings complement the reported results of the TAILORx trial, which showed that chemotherapy does not provide a benefit in most low and intermediate recurrence score tumors, which suggests some patients may safely omit chemotherapy without affecting outcomes, the investigators added.
The present analysis included a total of 30,864 grade 3 breast cancers from the National Cancer Database, which represents more than 70% of new diagnoses in the United States, according to investigators.
Testing using the 21-gene Oncotype DX Breast Recurrence Score increased over time for pN0 cancers, from 53% in 2010 to 72% in 2015, investigators found; likewise, for pN1 cancers, testing increased from 16% to 36% over that time period. They also found that, overall, 30% of pN0 and 27.1% of pN1 cancers had a low recurrence score.
Adjuvant chemotherapy was not associated with any additional benefit in patients with low recurrence scores, according to the analysis.
For patients with intermediate recurrence scores, chemotherapy was linked to improved survival in univariable analyses, but following adjustment for clinical and pathologic characteristics, intermediate scores were not predictive of a significant overall survival benefit, investigators found.
By contrast, chemotherapy was associated with additional benefit in patients with high recurrence scores in both univariable and multivariable analyses.
For patients with pN0 grade 3 disease and high recurrence score, chemotherapy was linked to significantly improved overall survival, compared with that of patients who received no chemotherapy (hazard ratio, 0.63; 95% confidence interval, 0.43-0.90; P = .01), while a similar survival benefit was reported among patients with pN1 disease and high recurrence scores (HR, 0.24; 95% CI, 0.13-0.47; P less than .001).
These results suggest that recurrence score may aid in determining the anticipated benefit of chemotherapy in this heterogeneous cohort of patients, investigators wrote.
“Furthermore, our findings show significant variability in national patterns of recurrence testing and chemotherapy use for grade 3 disease, which suggests opportunities for more comprehensive national guidelines for recurrence score testing in high-grade tumors,” they concluded.
Dr. Brock reported no potential conflicts of interest. Coauthors provided disclosures related to AstraZeneca, Blade Therapeutics, Eisai, EMD Serono, Galena Biopharma, Genentech, Genomic Health, Novartis, Novartis Institutes for BioMedical Research, Peregrine, Puma Biotechnology, resTORbio, Roche, and others.
SOURCE: Brock JE et al. JCO Precis Oncol. 2019 Aug 14. doi: 10.1200/PO.19.00029.
For patients with grade 3 breast cancer, recurrence score testing may have significant clinical value in determining which patients are likely to benefit from chemotherapy, according to investigators who recently reported results of a large, national cohort study.
Among patients with pN0/1 grade 3 invasive breast cancers, about one-third had a low recurrence score, which was associated with no early benefit from the addition of chemotherapy, wrote senior study author Jane E. Brock, MBBS, PhD, of Harvard Medical School, Boston, and coauthors.
Incorporating recurrence score testing into clinical decision making may help “tailor treatment recommendations” for patients with grade 3 invasive breast cancers, Dr. Brock and coauthors reported in JCO Precision Oncology.
“To our knowledge, these findings represent the largest analysis to date of the potential impact of recurrence score on the outcomes and management of grade 3 tumors, and suggest that the assumption that all pT1c/2 pN0/1, [estrogen receptor–positive] histopathologic grade 3 tumors are high risk and will consequently benefit from adjuvant chemotherapy may be unmerited,” the Dr. Brock and coauthors wrote in the report.
These findings “fill a gap” as the final results of the RxPONDER trial are awaited, according to investigators. Specifically, RxPONDER is designed to evaluate the potential benefit of adjuvant chemotherapy in pN0/1 patients with intermediate range recurrence scores.
Moreover, the findings complement the reported results of the TAILORx trial, which showed that chemotherapy does not provide a benefit in most low and intermediate recurrence score tumors, which suggests some patients may safely omit chemotherapy without affecting outcomes, the investigators added.
The present analysis included a total of 30,864 grade 3 breast cancers from the National Cancer Database, which represents more than 70% of new diagnoses in the United States, according to investigators.
Testing using the 21-gene Oncotype DX Breast Recurrence Score increased over time for pN0 cancers, from 53% in 2010 to 72% in 2015, investigators found; likewise, for pN1 cancers, testing increased from 16% to 36% over that time period. They also found that, overall, 30% of pN0 and 27.1% of pN1 cancers had a low recurrence score.
Adjuvant chemotherapy was not associated with any additional benefit in patients with low recurrence scores, according to the analysis.
For patients with intermediate recurrence scores, chemotherapy was linked to improved survival in univariable analyses, but following adjustment for clinical and pathologic characteristics, intermediate scores were not predictive of a significant overall survival benefit, investigators found.
By contrast, chemotherapy was associated with additional benefit in patients with high recurrence scores in both univariable and multivariable analyses.
For patients with pN0 grade 3 disease and high recurrence score, chemotherapy was linked to significantly improved overall survival, compared with that of patients who received no chemotherapy (hazard ratio, 0.63; 95% confidence interval, 0.43-0.90; P = .01), while a similar survival benefit was reported among patients with pN1 disease and high recurrence scores (HR, 0.24; 95% CI, 0.13-0.47; P less than .001).
These results suggest that recurrence score may aid in determining the anticipated benefit of chemotherapy in this heterogeneous cohort of patients, investigators wrote.
“Furthermore, our findings show significant variability in national patterns of recurrence testing and chemotherapy use for grade 3 disease, which suggests opportunities for more comprehensive national guidelines for recurrence score testing in high-grade tumors,” they concluded.
Dr. Brock reported no potential conflicts of interest. Coauthors provided disclosures related to AstraZeneca, Blade Therapeutics, Eisai, EMD Serono, Galena Biopharma, Genentech, Genomic Health, Novartis, Novartis Institutes for BioMedical Research, Peregrine, Puma Biotechnology, resTORbio, Roche, and others.
SOURCE: Brock JE et al. JCO Precis Oncol. 2019 Aug 14. doi: 10.1200/PO.19.00029.
FROM JCO PRECISION ONCOLOGY
USPSTF expands BRCA1/2 testing recommendations
The U.S. Preventive Services Task Force (USPSTF) has updated its recommendations on assessment of breast cancer susceptibility gene (BRCA)-related cancer, substantially expanding the pool of individuals for whom risk assessment, testing, and counseling would be warranted.
In its 2013 recommendation, the USPSTF said referral for genetic counseling and evaluation for BRCA1/2 testing was warranted for women who had a family history linked to increased risk of potentially harmful BRCA1/2 mutations.
The updated recommendations, just published in JAMA, expand the screening-eligible population to include those with personal cancer history, and more specifically call out ancestry linked to BRCA1/2 mutations as a risk factor (JAMA. 2019;322[7]:652-65. doi: 10.1001/jama.2019.10987).
“The USPSTF recommends that primary care clinicians assess women with a personal or family history of breast, ovarian, tubal, or peritoneal cancer or who have an ancestry associated with BRCA1/2 gene mutations with an appropriate brief familial risk assessment tool,” wrote Douglas K. Owens, MD, of Stanford (Calif.) University, and coauthors of the task force report.
Positive results on the risk assessment tool should prompt genetic counseling, and genetic testing if indicated after counseling, the USPSTF added in its statement.
By contrast, the task force recommends against routine assessment, counseling, and testing in women with no family history, personal history, or ancestry linked to possibly harmful BRCA1/2 gene mutations, consistent with their previous recommendation.
Mutations of BRCA1/2 genes occur in an estimated 1 in 300-500 women in the general population, and account for 15% of ovarian cancer and up to 10% of breast cancer cases, according to the USPSTF.
Breast cancer risk is increased up to 65% by 70 years in those women with clinically significant BRCA1/2 mutations, while risk of ovarian, fallopian tube, or peritoneal cancer are increased by up to 39%, according to studies cited by the USPSTF.
Important step forward
Including women with prior breast and ovarian cancer in the screening-eligible population is an “important step forward,” Susan Domcheck, MD, and Mark Robson, MD, said in a related editorial.
“While further expansion of the USPSTF recommendation should be considered, the importance is clear: Identification of individuals at risk of carrying a BRCA1/2 mutation can be lifesaving and should be a part of routine medical care,” Dr. Domcheck and Dr. Robson said in their editorial, which appears in JAMA.
While the updated recommendations explicitly call out ancestry as a risk factor, they stop short of endorsing testing for unaffected Ashkenazi Jewish women with no family history, the authors said.
“However, the statement may be interpreted as a step toward supporting unselected testing in this group,” they added.
Among unselected individuals of Ashkenazi Jewish descent, 1 in 40 have 1 of 3 specific BRCA1 or BRCA2 founder mutations, according to one study cited by Dr. Domcheck and Dr. Robson.
More research needed
Current research is still “limited or lacking” to address many key questions about the benefits and harms of risk assessment, genetic counseling, and genetic testing in women without BRCA1/2-related cancer, according to authors of a literature review used by the USPSTF.
Notably, the ability of risk assessment, testing, and counseling to reduce cancer incidence and mortality among such women has not been directly evaluated by studies to date, said the review authors, led by Heidi D. Nelson, MD, MPH, of Oregon Health & Science University, Portland.
“Without effectiveness trials of intensive screening, practice standards have preceded supporting evidence,” said Dr. Nelson and coauthors noted in a report on the review findings.
In observational studies, mastectomy and oophorectomy have been associated with substantial reductions in subsequent cancer incidence and mortality; however, they are invasive procedures with potential complications, the authors noted.
“To determine the appropriateness of risk assessment and genetic testing for BRCA1/2 mutations as a preventive service in primary care, more information is needed about mutation prevalence and the effect of testing in the general population,” they added.
Researchers studying BRCA1/2 assessment as preventive service in primary care have generally looked at highly selected patient populations in referral centers, and have reported relatively short-term outcomes, they said.
Research is additionally needed on access to genetic testing and follow-up, effectiveness of risk stratification and multigene panels, and the impact of direct-to-consumer genetic testing, among other key questions, the authors of the review added.
Treatment implications
While the USPSTF recommendations do not mention systemic therapy, finding a BRCA mutation in a cancer patient today has important implications for treatment, said Rachel L. Yung, MD, and Larissa A. Korde, MD, MPH
Specifically, poly (ADP-ribose) polymerase (PARP) inhibitors have proved effective in certain BRCA-related cancers, Dr. Yung and Dr. Korde said in an editorial on the updated recommendations appearing in JAMA Oncology.
The Food and Drug Administration has already approved several PARP inhibitors for treatment of BRCA-linked metastatic breast or ovarian cancers, and studies are underway for other tumor types, including prostate and pancreatic cancers that harbor a BRCA mutation.
“Increasing awareness of BRCA mutation as a target for treatment will likely lead to an increase in the identification of patients with cancer harboring germline BRCA mutations, which in turn will increase the need for cascade testing for relatives of affected probands,” wrote Dr. Yung and Dr. Korde.
Addressing disparities in care
The USPSTF recommendations for BRCA risk assessment do not address disparities in testing referral and variation in breast cancer phenotypes among women of African ancestry, owing to lack of evidence, according to Lisa Newman, MD, MPH, of the Interdisciplinary Breast Program at New York–Presbyterian/Weill Cornell Medical Center, New York.
“Paradoxically, the data-driven basis for the USPSTF recommendation statement may magnify existing genetic testing disparities,” Dr. Newman wrote in an editorial that appears in JAMA Surgery.
Non-Hispanic black women in the United States have a twofold higher incidence of triple-negative breast cancer, which is a well documented risk factor for BRCA1 mutation carrier status, according to Dr. Newman.
Despite this, she added, genetic counseling and testing referrals remain “disproportionately low” among U.S. patients of African ancestry.
“It remains imperative for clinicians to exercise clinical judgment and to be mindful of patient subsets that do not necessarily fit into recommendations designed for the majority or general populations,” Dr. Newman concluded in her editorial.
The USPSTF is funded by the Agency for Healthcare Research and Quality. Members of the task force receive travel reimbursement and honoraria for participating in USPSTF meetings.
The U.S. Preventive Services Task Force (USPSTF) has updated its recommendations on assessment of breast cancer susceptibility gene (BRCA)-related cancer, substantially expanding the pool of individuals for whom risk assessment, testing, and counseling would be warranted.
In its 2013 recommendation, the USPSTF said referral for genetic counseling and evaluation for BRCA1/2 testing was warranted for women who had a family history linked to increased risk of potentially harmful BRCA1/2 mutations.
The updated recommendations, just published in JAMA, expand the screening-eligible population to include those with personal cancer history, and more specifically call out ancestry linked to BRCA1/2 mutations as a risk factor (JAMA. 2019;322[7]:652-65. doi: 10.1001/jama.2019.10987).
“The USPSTF recommends that primary care clinicians assess women with a personal or family history of breast, ovarian, tubal, or peritoneal cancer or who have an ancestry associated with BRCA1/2 gene mutations with an appropriate brief familial risk assessment tool,” wrote Douglas K. Owens, MD, of Stanford (Calif.) University, and coauthors of the task force report.
Positive results on the risk assessment tool should prompt genetic counseling, and genetic testing if indicated after counseling, the USPSTF added in its statement.
By contrast, the task force recommends against routine assessment, counseling, and testing in women with no family history, personal history, or ancestry linked to possibly harmful BRCA1/2 gene mutations, consistent with their previous recommendation.
Mutations of BRCA1/2 genes occur in an estimated 1 in 300-500 women in the general population, and account for 15% of ovarian cancer and up to 10% of breast cancer cases, according to the USPSTF.
Breast cancer risk is increased up to 65% by 70 years in those women with clinically significant BRCA1/2 mutations, while risk of ovarian, fallopian tube, or peritoneal cancer are increased by up to 39%, according to studies cited by the USPSTF.
Important step forward
Including women with prior breast and ovarian cancer in the screening-eligible population is an “important step forward,” Susan Domcheck, MD, and Mark Robson, MD, said in a related editorial.
“While further expansion of the USPSTF recommendation should be considered, the importance is clear: Identification of individuals at risk of carrying a BRCA1/2 mutation can be lifesaving and should be a part of routine medical care,” Dr. Domcheck and Dr. Robson said in their editorial, which appears in JAMA.
While the updated recommendations explicitly call out ancestry as a risk factor, they stop short of endorsing testing for unaffected Ashkenazi Jewish women with no family history, the authors said.
“However, the statement may be interpreted as a step toward supporting unselected testing in this group,” they added.
Among unselected individuals of Ashkenazi Jewish descent, 1 in 40 have 1 of 3 specific BRCA1 or BRCA2 founder mutations, according to one study cited by Dr. Domcheck and Dr. Robson.
More research needed
Current research is still “limited or lacking” to address many key questions about the benefits and harms of risk assessment, genetic counseling, and genetic testing in women without BRCA1/2-related cancer, according to authors of a literature review used by the USPSTF.
Notably, the ability of risk assessment, testing, and counseling to reduce cancer incidence and mortality among such women has not been directly evaluated by studies to date, said the review authors, led by Heidi D. Nelson, MD, MPH, of Oregon Health & Science University, Portland.
“Without effectiveness trials of intensive screening, practice standards have preceded supporting evidence,” said Dr. Nelson and coauthors noted in a report on the review findings.
In observational studies, mastectomy and oophorectomy have been associated with substantial reductions in subsequent cancer incidence and mortality; however, they are invasive procedures with potential complications, the authors noted.
“To determine the appropriateness of risk assessment and genetic testing for BRCA1/2 mutations as a preventive service in primary care, more information is needed about mutation prevalence and the effect of testing in the general population,” they added.
Researchers studying BRCA1/2 assessment as preventive service in primary care have generally looked at highly selected patient populations in referral centers, and have reported relatively short-term outcomes, they said.
Research is additionally needed on access to genetic testing and follow-up, effectiveness of risk stratification and multigene panels, and the impact of direct-to-consumer genetic testing, among other key questions, the authors of the review added.
Treatment implications
While the USPSTF recommendations do not mention systemic therapy, finding a BRCA mutation in a cancer patient today has important implications for treatment, said Rachel L. Yung, MD, and Larissa A. Korde, MD, MPH
Specifically, poly (ADP-ribose) polymerase (PARP) inhibitors have proved effective in certain BRCA-related cancers, Dr. Yung and Dr. Korde said in an editorial on the updated recommendations appearing in JAMA Oncology.
The Food and Drug Administration has already approved several PARP inhibitors for treatment of BRCA-linked metastatic breast or ovarian cancers, and studies are underway for other tumor types, including prostate and pancreatic cancers that harbor a BRCA mutation.
“Increasing awareness of BRCA mutation as a target for treatment will likely lead to an increase in the identification of patients with cancer harboring germline BRCA mutations, which in turn will increase the need for cascade testing for relatives of affected probands,” wrote Dr. Yung and Dr. Korde.
Addressing disparities in care
The USPSTF recommendations for BRCA risk assessment do not address disparities in testing referral and variation in breast cancer phenotypes among women of African ancestry, owing to lack of evidence, according to Lisa Newman, MD, MPH, of the Interdisciplinary Breast Program at New York–Presbyterian/Weill Cornell Medical Center, New York.
“Paradoxically, the data-driven basis for the USPSTF recommendation statement may magnify existing genetic testing disparities,” Dr. Newman wrote in an editorial that appears in JAMA Surgery.
Non-Hispanic black women in the United States have a twofold higher incidence of triple-negative breast cancer, which is a well documented risk factor for BRCA1 mutation carrier status, according to Dr. Newman.
Despite this, she added, genetic counseling and testing referrals remain “disproportionately low” among U.S. patients of African ancestry.
“It remains imperative for clinicians to exercise clinical judgment and to be mindful of patient subsets that do not necessarily fit into recommendations designed for the majority or general populations,” Dr. Newman concluded in her editorial.
The USPSTF is funded by the Agency for Healthcare Research and Quality. Members of the task force receive travel reimbursement and honoraria for participating in USPSTF meetings.
The U.S. Preventive Services Task Force (USPSTF) has updated its recommendations on assessment of breast cancer susceptibility gene (BRCA)-related cancer, substantially expanding the pool of individuals for whom risk assessment, testing, and counseling would be warranted.
In its 2013 recommendation, the USPSTF said referral for genetic counseling and evaluation for BRCA1/2 testing was warranted for women who had a family history linked to increased risk of potentially harmful BRCA1/2 mutations.
The updated recommendations, just published in JAMA, expand the screening-eligible population to include those with personal cancer history, and more specifically call out ancestry linked to BRCA1/2 mutations as a risk factor (JAMA. 2019;322[7]:652-65. doi: 10.1001/jama.2019.10987).
“The USPSTF recommends that primary care clinicians assess women with a personal or family history of breast, ovarian, tubal, or peritoneal cancer or who have an ancestry associated with BRCA1/2 gene mutations with an appropriate brief familial risk assessment tool,” wrote Douglas K. Owens, MD, of Stanford (Calif.) University, and coauthors of the task force report.
Positive results on the risk assessment tool should prompt genetic counseling, and genetic testing if indicated after counseling, the USPSTF added in its statement.
By contrast, the task force recommends against routine assessment, counseling, and testing in women with no family history, personal history, or ancestry linked to possibly harmful BRCA1/2 gene mutations, consistent with their previous recommendation.
Mutations of BRCA1/2 genes occur in an estimated 1 in 300-500 women in the general population, and account for 15% of ovarian cancer and up to 10% of breast cancer cases, according to the USPSTF.
Breast cancer risk is increased up to 65% by 70 years in those women with clinically significant BRCA1/2 mutations, while risk of ovarian, fallopian tube, or peritoneal cancer are increased by up to 39%, according to studies cited by the USPSTF.
Important step forward
Including women with prior breast and ovarian cancer in the screening-eligible population is an “important step forward,” Susan Domcheck, MD, and Mark Robson, MD, said in a related editorial.
“While further expansion of the USPSTF recommendation should be considered, the importance is clear: Identification of individuals at risk of carrying a BRCA1/2 mutation can be lifesaving and should be a part of routine medical care,” Dr. Domcheck and Dr. Robson said in their editorial, which appears in JAMA.
While the updated recommendations explicitly call out ancestry as a risk factor, they stop short of endorsing testing for unaffected Ashkenazi Jewish women with no family history, the authors said.
“However, the statement may be interpreted as a step toward supporting unselected testing in this group,” they added.
Among unselected individuals of Ashkenazi Jewish descent, 1 in 40 have 1 of 3 specific BRCA1 or BRCA2 founder mutations, according to one study cited by Dr. Domcheck and Dr. Robson.
More research needed
Current research is still “limited or lacking” to address many key questions about the benefits and harms of risk assessment, genetic counseling, and genetic testing in women without BRCA1/2-related cancer, according to authors of a literature review used by the USPSTF.
Notably, the ability of risk assessment, testing, and counseling to reduce cancer incidence and mortality among such women has not been directly evaluated by studies to date, said the review authors, led by Heidi D. Nelson, MD, MPH, of Oregon Health & Science University, Portland.
“Without effectiveness trials of intensive screening, practice standards have preceded supporting evidence,” said Dr. Nelson and coauthors noted in a report on the review findings.
In observational studies, mastectomy and oophorectomy have been associated with substantial reductions in subsequent cancer incidence and mortality; however, they are invasive procedures with potential complications, the authors noted.
“To determine the appropriateness of risk assessment and genetic testing for BRCA1/2 mutations as a preventive service in primary care, more information is needed about mutation prevalence and the effect of testing in the general population,” they added.
Researchers studying BRCA1/2 assessment as preventive service in primary care have generally looked at highly selected patient populations in referral centers, and have reported relatively short-term outcomes, they said.
Research is additionally needed on access to genetic testing and follow-up, effectiveness of risk stratification and multigene panels, and the impact of direct-to-consumer genetic testing, among other key questions, the authors of the review added.
Treatment implications
While the USPSTF recommendations do not mention systemic therapy, finding a BRCA mutation in a cancer patient today has important implications for treatment, said Rachel L. Yung, MD, and Larissa A. Korde, MD, MPH
Specifically, poly (ADP-ribose) polymerase (PARP) inhibitors have proved effective in certain BRCA-related cancers, Dr. Yung and Dr. Korde said in an editorial on the updated recommendations appearing in JAMA Oncology.
The Food and Drug Administration has already approved several PARP inhibitors for treatment of BRCA-linked metastatic breast or ovarian cancers, and studies are underway for other tumor types, including prostate and pancreatic cancers that harbor a BRCA mutation.
“Increasing awareness of BRCA mutation as a target for treatment will likely lead to an increase in the identification of patients with cancer harboring germline BRCA mutations, which in turn will increase the need for cascade testing for relatives of affected probands,” wrote Dr. Yung and Dr. Korde.
Addressing disparities in care
The USPSTF recommendations for BRCA risk assessment do not address disparities in testing referral and variation in breast cancer phenotypes among women of African ancestry, owing to lack of evidence, according to Lisa Newman, MD, MPH, of the Interdisciplinary Breast Program at New York–Presbyterian/Weill Cornell Medical Center, New York.
“Paradoxically, the data-driven basis for the USPSTF recommendation statement may magnify existing genetic testing disparities,” Dr. Newman wrote in an editorial that appears in JAMA Surgery.
Non-Hispanic black women in the United States have a twofold higher incidence of triple-negative breast cancer, which is a well documented risk factor for BRCA1 mutation carrier status, according to Dr. Newman.
Despite this, she added, genetic counseling and testing referrals remain “disproportionately low” among U.S. patients of African ancestry.
“It remains imperative for clinicians to exercise clinical judgment and to be mindful of patient subsets that do not necessarily fit into recommendations designed for the majority or general populations,” Dr. Newman concluded in her editorial.
The USPSTF is funded by the Agency for Healthcare Research and Quality. Members of the task force receive travel reimbursement and honoraria for participating in USPSTF meetings.
FROM JAMA
Tamoxifen benefit in lower-risk breast cancer varies by intrinsic subtype
, finds a secondary analysis of the Stockholm Tamoxifen (STO-3) trial.
“Patients with estrogen receptor (ER)–positive breast cancer have a long-term risk for fatal disease. However, the tumor biological factors that influence the long-term risk and the benefit associated with endocrine therapy are not well understood,” noted the investigators, who conducted the research under senior investigator Linda Lindström, MSc, PhD, department of biosciences and nutrition, Karolinska Institutet, Stockholm.
The STO-3 trial spanned 1976 to 1990 and randomized postmenopausal patients with lymph node–negative breast cancer to receive at least 2 years of adjuvant tamoxifen or no endocrine therapy.
Dr. Lindström and coinvestigators used immunohistochemistry and Agilent microarrays to define tumor molecular subtype. Analyses were based on 462 patients with ER-positive disease: 336 with luminal A subtype tumors and 126 with luminal B subtype tumors.
Results reported in JAMA Oncology showed that the distant recurrence–free interval (DRFI) was significantly better with tamoxifen than with no endocrine therapy in both the luminal A group (P less than .001) and the luminal B group (P = .04).
Among patients given tamoxifen, the 25-year DRFI rate was 87% (95% confidence interval, 82%-93%) for those with luminal A tumors vs. 67% (95% CI, 56%-82%) for those with luminal B tumors. Among patients not given any endocrine therapy, it was 70% (95% CI, 62%-79%) vs. 54% (95% CI, 42%-70%), respectively.
Tamoxifen had a significant DRFI benefit for 15 years after diagnosis in the luminal A group (hazard ratio, 0.57; 95% CI, 0.35-0.94). In contrast, the benefit was significant for only 5 years in the luminal B group (HR, 0.38; 95% CI, 0.24-0.59).
“We conclude that tamoxifen appears to confer a long-term benefit for patients with lymph node–negative, ER-positive, luminal A subtype tumors, and a short-term benefit for patients with luminal B subtype tumors. Given that the risk of distant metastatic disease is low for patients with the luminal A subtype but persists in the long term, whereas the risk for patients with luminal B subtype is higher initially but decreases after 5 years, tamoxifen treatment is beneficial for patients with luminal A or luminal B subtype tumors,” Dr. Lindström and coinvestigators maintained.
“In patients with luminal B subtype, up-front chemotherapy should be discussed and endocrine therapy potentially extended for up to 10 years, particularly in those in the higher risk strata according to other tumor characteristics,” they recommended.
Dr. Lindström disclosed no conflicts of interest. The study was supported by the Swedish Research Council, FORTE, The Gösta Milton Donation Fund, the California Breast Cancer Research Program, The Iris, Stig och Gerry Castenbäcks Stiftelse för Cancerforskning, and Konung Gustaf V:s Jubileumsfond from Radiumhemmets Forskningsfonder.
SOURCE: Yu NY et al. JAMA Oncol. 2019 Aug 8. doi: 10.1001/jamaoncol.2019.1856.
, finds a secondary analysis of the Stockholm Tamoxifen (STO-3) trial.
“Patients with estrogen receptor (ER)–positive breast cancer have a long-term risk for fatal disease. However, the tumor biological factors that influence the long-term risk and the benefit associated with endocrine therapy are not well understood,” noted the investigators, who conducted the research under senior investigator Linda Lindström, MSc, PhD, department of biosciences and nutrition, Karolinska Institutet, Stockholm.
The STO-3 trial spanned 1976 to 1990 and randomized postmenopausal patients with lymph node–negative breast cancer to receive at least 2 years of adjuvant tamoxifen or no endocrine therapy.
Dr. Lindström and coinvestigators used immunohistochemistry and Agilent microarrays to define tumor molecular subtype. Analyses were based on 462 patients with ER-positive disease: 336 with luminal A subtype tumors and 126 with luminal B subtype tumors.
Results reported in JAMA Oncology showed that the distant recurrence–free interval (DRFI) was significantly better with tamoxifen than with no endocrine therapy in both the luminal A group (P less than .001) and the luminal B group (P = .04).
Among patients given tamoxifen, the 25-year DRFI rate was 87% (95% confidence interval, 82%-93%) for those with luminal A tumors vs. 67% (95% CI, 56%-82%) for those with luminal B tumors. Among patients not given any endocrine therapy, it was 70% (95% CI, 62%-79%) vs. 54% (95% CI, 42%-70%), respectively.
Tamoxifen had a significant DRFI benefit for 15 years after diagnosis in the luminal A group (hazard ratio, 0.57; 95% CI, 0.35-0.94). In contrast, the benefit was significant for only 5 years in the luminal B group (HR, 0.38; 95% CI, 0.24-0.59).
“We conclude that tamoxifen appears to confer a long-term benefit for patients with lymph node–negative, ER-positive, luminal A subtype tumors, and a short-term benefit for patients with luminal B subtype tumors. Given that the risk of distant metastatic disease is low for patients with the luminal A subtype but persists in the long term, whereas the risk for patients with luminal B subtype is higher initially but decreases after 5 years, tamoxifen treatment is beneficial for patients with luminal A or luminal B subtype tumors,” Dr. Lindström and coinvestigators maintained.
“In patients with luminal B subtype, up-front chemotherapy should be discussed and endocrine therapy potentially extended for up to 10 years, particularly in those in the higher risk strata according to other tumor characteristics,” they recommended.
Dr. Lindström disclosed no conflicts of interest. The study was supported by the Swedish Research Council, FORTE, The Gösta Milton Donation Fund, the California Breast Cancer Research Program, The Iris, Stig och Gerry Castenbäcks Stiftelse för Cancerforskning, and Konung Gustaf V:s Jubileumsfond from Radiumhemmets Forskningsfonder.
SOURCE: Yu NY et al. JAMA Oncol. 2019 Aug 8. doi: 10.1001/jamaoncol.2019.1856.
, finds a secondary analysis of the Stockholm Tamoxifen (STO-3) trial.
“Patients with estrogen receptor (ER)–positive breast cancer have a long-term risk for fatal disease. However, the tumor biological factors that influence the long-term risk and the benefit associated with endocrine therapy are not well understood,” noted the investigators, who conducted the research under senior investigator Linda Lindström, MSc, PhD, department of biosciences and nutrition, Karolinska Institutet, Stockholm.
The STO-3 trial spanned 1976 to 1990 and randomized postmenopausal patients with lymph node–negative breast cancer to receive at least 2 years of adjuvant tamoxifen or no endocrine therapy.
Dr. Lindström and coinvestigators used immunohistochemistry and Agilent microarrays to define tumor molecular subtype. Analyses were based on 462 patients with ER-positive disease: 336 with luminal A subtype tumors and 126 with luminal B subtype tumors.
Results reported in JAMA Oncology showed that the distant recurrence–free interval (DRFI) was significantly better with tamoxifen than with no endocrine therapy in both the luminal A group (P less than .001) and the luminal B group (P = .04).
Among patients given tamoxifen, the 25-year DRFI rate was 87% (95% confidence interval, 82%-93%) for those with luminal A tumors vs. 67% (95% CI, 56%-82%) for those with luminal B tumors. Among patients not given any endocrine therapy, it was 70% (95% CI, 62%-79%) vs. 54% (95% CI, 42%-70%), respectively.
Tamoxifen had a significant DRFI benefit for 15 years after diagnosis in the luminal A group (hazard ratio, 0.57; 95% CI, 0.35-0.94). In contrast, the benefit was significant for only 5 years in the luminal B group (HR, 0.38; 95% CI, 0.24-0.59).
“We conclude that tamoxifen appears to confer a long-term benefit for patients with lymph node–negative, ER-positive, luminal A subtype tumors, and a short-term benefit for patients with luminal B subtype tumors. Given that the risk of distant metastatic disease is low for patients with the luminal A subtype but persists in the long term, whereas the risk for patients with luminal B subtype is higher initially but decreases after 5 years, tamoxifen treatment is beneficial for patients with luminal A or luminal B subtype tumors,” Dr. Lindström and coinvestigators maintained.
“In patients with luminal B subtype, up-front chemotherapy should be discussed and endocrine therapy potentially extended for up to 10 years, particularly in those in the higher risk strata according to other tumor characteristics,” they recommended.
Dr. Lindström disclosed no conflicts of interest. The study was supported by the Swedish Research Council, FORTE, The Gösta Milton Donation Fund, the California Breast Cancer Research Program, The Iris, Stig och Gerry Castenbäcks Stiftelse för Cancerforskning, and Konung Gustaf V:s Jubileumsfond from Radiumhemmets Forskningsfonder.
SOURCE: Yu NY et al. JAMA Oncol. 2019 Aug 8. doi: 10.1001/jamaoncol.2019.1856.
FROM JAMA ONCOLOGY