Breast Cancer

Disease progression is associated with worsening health-related quality of life (HRQOL) among patients with metastatic cancers, results of an observational study suggest.

The findings highlight the importance of patient-relevant outcomes when evaluating novel therapies for patients with metastatic cancers, according to Norbert Marschner, MD, of Praxis für interdisziplinäre onkologie und hämatologie in Freiburg, Germany, and colleagues. The researchers reported the findings in JAMA Network Open.

They used four nationwide German registries to evaluate the association of disease progression with HRQOL in patients receiving systemic therapy for metastatic colorectal, lung, pancreatic, or breast cancer.

The analysis included 2,314 adults with documented disease progression across 203 institutions in Germany. Data collection occurred during routine follow-up visits at participating centers during 2011-2018.

Various patient-reported outcome questionnaires were used to measure HRQOL and symptom severity among participants. For the present study, the team enrolled patients at the start of any systemic palliative treatment, defined as targeted therapy, chemotherapy, or endocrine therapy.

Mixed-model analyses of more than 8,000 questionnaires showed that the first disease progression was associated with significant deterioration in 37 of 45 HRQOL scales overall, 17 of which were considered clinically meaningful.

With respect to cancer type, significant worsening after the first progression occurred in 12 of 14 colorectal cancer HRQOL scales, 11 of 14 lung cancer scales, 10 of 10 pancreatic cancer scales, and 4 of 7 breast cancer scales.

The deterioration in global HRQOL associated with the first progression was of greatest magnitude in lung cancer (6.7 points; P < .001), followed by pancreatic cancer (5.4 points; P < .001), colorectal cancer (3.5 points; P = .002), and breast cancer (2.4 points; P = .001).

The researchers also found that 38 of 45 HRQOL scales showed a greater degree of worsening after the second disease progression than after the first. They observed significant worsening after the second disease progression in 32 of 45 HRQOL scales, and all 32 were considered clinically meaningful.

The researchers acknowledged that a key limitation of this study was the observational design. As a result, the study did not include specifications related to tumor assessment, such as frequency, timing, or criteria.

“We suggest that progression-related endpoints in metastatic breast, colorectal, lung, or pancreatic cancer should be considered when evaluating the benefit of novel treatments, in addition to survival, morbidity, and HRQOL outcomes,” the researchers concluded.

The registries used in this study are funded by iOMEDICO and industry sponsors. The authors disclosed relationships with iOMEDICO and several pharmaceutical companies.

SOURCE: Marschner N et al. JAMA Netw Open. 2020 Mar 10. doi: 10.1001/jamanetworkopen.2020.0643.

Disease progression is associated with worsening health-related quality of life (HRQOL) among patients with metastatic cancers, results of an observational study suggest.

The findings highlight the importance of patient-relevant outcomes when evaluating novel therapies for patients with metastatic cancers, according to Norbert Marschner, MD, of Praxis für interdisziplinäre onkologie und hämatologie in Freiburg, Germany, and colleagues. The researchers reported the findings in JAMA Network Open.

They used four nationwide German registries to evaluate the association of disease progression with HRQOL in patients receiving systemic therapy for metastatic colorectal, lung, pancreatic, or breast cancer.

The analysis included 2,314 adults with documented disease progression across 203 institutions in Germany. Data collection occurred during routine follow-up visits at participating centers during 2011-2018.

Various patient-reported outcome questionnaires were used to measure HRQOL and symptom severity among participants. For the present study, the team enrolled patients at the start of any systemic palliative treatment, defined as targeted therapy, chemotherapy, or endocrine therapy.

Mixed-model analyses of more than 8,000 questionnaires showed that the first disease progression was associated with significant deterioration in 37 of 45 HRQOL scales overall, 17 of which were considered clinically meaningful.

With respect to cancer type, significant worsening after the first progression occurred in 12 of 14 colorectal cancer HRQOL scales, 11 of 14 lung cancer scales, 10 of 10 pancreatic cancer scales, and 4 of 7 breast cancer scales.

The deterioration in global HRQOL associated with the first progression was of greatest magnitude in lung cancer (6.7 points; P < .001), followed by pancreatic cancer (5.4 points; P < .001), colorectal cancer (3.5 points; P = .002), and breast cancer (2.4 points; P = .001).

The researchers also found that 38 of 45 HRQOL scales showed a greater degree of worsening after the second disease progression than after the first. They observed significant worsening after the second disease progression in 32 of 45 HRQOL scales, and all 32 were considered clinically meaningful.

The researchers acknowledged that a key limitation of this study was the observational design. As a result, the study did not include specifications related to tumor assessment, such as frequency, timing, or criteria.

“We suggest that progression-related endpoints in metastatic breast, colorectal, lung, or pancreatic cancer should be considered when evaluating the benefit of novel treatments, in addition to survival, morbidity, and HRQOL outcomes,” the researchers concluded.

The registries used in this study are funded by iOMEDICO and industry sponsors. The authors disclosed relationships with iOMEDICO and several pharmaceutical companies.

SOURCE: Marschner N et al. JAMA Netw Open. 2020 Mar 10. doi: 10.1001/jamanetworkopen.2020.0643.

Disease progression is associated with worsening health-related quality of life (HRQOL) among patients with metastatic cancers, results of an observational study suggest.

The findings highlight the importance of patient-relevant outcomes when evaluating novel therapies for patients with metastatic cancers, according to Norbert Marschner, MD, of Praxis für interdisziplinäre onkologie und hämatologie in Freiburg, Germany, and colleagues. The researchers reported the findings in JAMA Network Open.

They used four nationwide German registries to evaluate the association of disease progression with HRQOL in patients receiving systemic therapy for metastatic colorectal, lung, pancreatic, or breast cancer.

The analysis included 2,314 adults with documented disease progression across 203 institutions in Germany. Data collection occurred during routine follow-up visits at participating centers during 2011-2018.

Various patient-reported outcome questionnaires were used to measure HRQOL and symptom severity among participants. For the present study, the team enrolled patients at the start of any systemic palliative treatment, defined as targeted therapy, chemotherapy, or endocrine therapy.

Mixed-model analyses of more than 8,000 questionnaires showed that the first disease progression was associated with significant deterioration in 37 of 45 HRQOL scales overall, 17 of which were considered clinically meaningful.

With respect to cancer type, significant worsening after the first progression occurred in 12 of 14 colorectal cancer HRQOL scales, 11 of 14 lung cancer scales, 10 of 10 pancreatic cancer scales, and 4 of 7 breast cancer scales.

The deterioration in global HRQOL associated with the first progression was of greatest magnitude in lung cancer (6.7 points; P < .001), followed by pancreatic cancer (5.4 points; P < .001), colorectal cancer (3.5 points; P = .002), and breast cancer (2.4 points; P = .001).

The researchers also found that 38 of 45 HRQOL scales showed a greater degree of worsening after the second disease progression than after the first. They observed significant worsening after the second disease progression in 32 of 45 HRQOL scales, and all 32 were considered clinically meaningful.

The researchers acknowledged that a key limitation of this study was the observational design. As a result, the study did not include specifications related to tumor assessment, such as frequency, timing, or criteria.

“We suggest that progression-related endpoints in metastatic breast, colorectal, lung, or pancreatic cancer should be considered when evaluating the benefit of novel treatments, in addition to survival, morbidity, and HRQOL outcomes,” the researchers concluded.

The registries used in this study are funded by iOMEDICO and industry sponsors. The authors disclosed relationships with iOMEDICO and several pharmaceutical companies.

SOURCE: Marschner N et al. JAMA Netw Open. 2020 Mar 10. doi: 10.1001/jamanetworkopen.2020.0643.

The International Association for the Study of Lung Cancer (IASLC) is naming the Translational Research Lectureship Award after Fred R. Hirsch, MD, PhD, of the Tisch Cancer Institute and Icahn School of Medicine at Mount Sinai, New York.

Dr. Hirsch was a longtime member of the IASLC and served as chief executive officer of the association from 2013 through October 2018. During this time, Dr. Hirsch grew the IASLC staff from 5 to 23 people and doubled the organization’s membership. The IASLC World Conference on Lung Cancer became an annual meeting under Dr. Hirsch’s direction and reported record attendance, according to their website.

The recipient of the Fred R. Hirsch Lectureship Award for Translational Research will be recognized at the IASLC 2020 World Conference on Lung Cancer, which is set to take place in Singapore on August 9-12, 2020.

In other news, the American Cancer Society (ACS) announced that it has awarded the 2020 Medal of Honor to three researchers. The recipients will be recognized at a black-tie ceremony in New York on Nov. 11, 2020.

Lewis C. Cantley, PhD, of Weill Cornell Medicine, New York, won the Medal of Honor for Basic Research. This award honors researchers whose work will have a “lasting impact on the cancer field” or who have made important discoveries or inventions within the field, according to the ACS.

Dr. Cantley won the award for research that has improved our understanding of cancer metabolism. He is known for his contributions to the discovery and study of phosphoinositide 3-kinase, which plays a role in many cancers and has become a target for therapies.

Leslie Bernstein, PhD, of City of Hope National Medical Center in Duarte, Calif., has won the Medal of Honor in Cancer Control. This award honors individuals who have made strides in public health, public communication, or public policy that have had an impact on cancer control.

Dr. Bernstein won the award for her work linking physical activity to a reduced risk of breast cancer. She is currently investigating links between hormone exposures, physical activity, obesity, and cancer, as well as examining how breast cancer impacts patients’ lives after treatment.

Ching-Hon Pui, MD, of St. Jude Children’s Research Hospital in Memphis, Tenn., has won the Medal of Honor in Clinical Research. This award honors researchers whose work has significantly improved cancer patients’ outcomes.

Dr. Pui won the award for his work in childhood acute lymphoblastic leukemia. Dr. Pui’s work has led to increased global treatment access, improved survival rates, and better quality of life for patients with childhood acute lymphoblastic leukemia.

[email protected]

The International Association for the Study of Lung Cancer (IASLC) is naming the Translational Research Lectureship Award after Fred R. Hirsch, MD, PhD, of the Tisch Cancer Institute and Icahn School of Medicine at Mount Sinai, New York.

Dr. Hirsch was a longtime member of the IASLC and served as chief executive officer of the association from 2013 through October 2018. During this time, Dr. Hirsch grew the IASLC staff from 5 to 23 people and doubled the organization’s membership. The IASLC World Conference on Lung Cancer became an annual meeting under Dr. Hirsch’s direction and reported record attendance, according to their website.

The recipient of the Fred R. Hirsch Lectureship Award for Translational Research will be recognized at the IASLC 2020 World Conference on Lung Cancer, which is set to take place in Singapore on August 9-12, 2020.

In other news, the American Cancer Society (ACS) announced that it has awarded the 2020 Medal of Honor to three researchers. The recipients will be recognized at a black-tie ceremony in New York on Nov. 11, 2020.

Lewis C. Cantley, PhD, of Weill Cornell Medicine, New York, won the Medal of Honor for Basic Research. This award honors researchers whose work will have a “lasting impact on the cancer field” or who have made important discoveries or inventions within the field, according to the ACS.

Dr. Cantley won the award for research that has improved our understanding of cancer metabolism. He is known for his contributions to the discovery and study of phosphoinositide 3-kinase, which plays a role in many cancers and has become a target for therapies.

Leslie Bernstein, PhD, of City of Hope National Medical Center in Duarte, Calif., has won the Medal of Honor in Cancer Control. This award honors individuals who have made strides in public health, public communication, or public policy that have had an impact on cancer control.

Dr. Bernstein won the award for her work linking physical activity to a reduced risk of breast cancer. She is currently investigating links between hormone exposures, physical activity, obesity, and cancer, as well as examining how breast cancer impacts patients’ lives after treatment.

Ching-Hon Pui, MD, of St. Jude Children’s Research Hospital in Memphis, Tenn., has won the Medal of Honor in Clinical Research. This award honors researchers whose work has significantly improved cancer patients’ outcomes.

Dr. Pui won the award for his work in childhood acute lymphoblastic leukemia. Dr. Pui’s work has led to increased global treatment access, improved survival rates, and better quality of life for patients with childhood acute lymphoblastic leukemia.

[email protected]

The International Association for the Study of Lung Cancer (IASLC) is naming the Translational Research Lectureship Award after Fred R. Hirsch, MD, PhD, of the Tisch Cancer Institute and Icahn School of Medicine at Mount Sinai, New York.

Dr. Hirsch was a longtime member of the IASLC and served as chief executive officer of the association from 2013 through October 2018. During this time, Dr. Hirsch grew the IASLC staff from 5 to 23 people and doubled the organization’s membership. The IASLC World Conference on Lung Cancer became an annual meeting under Dr. Hirsch’s direction and reported record attendance, according to their website.

The recipient of the Fred R. Hirsch Lectureship Award for Translational Research will be recognized at the IASLC 2020 World Conference on Lung Cancer, which is set to take place in Singapore on August 9-12, 2020.

In other news, the American Cancer Society (ACS) announced that it has awarded the 2020 Medal of Honor to three researchers. The recipients will be recognized at a black-tie ceremony in New York on Nov. 11, 2020.

Lewis C. Cantley, PhD, of Weill Cornell Medicine, New York, won the Medal of Honor for Basic Research. This award honors researchers whose work will have a “lasting impact on the cancer field” or who have made important discoveries or inventions within the field, according to the ACS.

Dr. Cantley won the award for research that has improved our understanding of cancer metabolism. He is known for his contributions to the discovery and study of phosphoinositide 3-kinase, which plays a role in many cancers and has become a target for therapies.

Leslie Bernstein, PhD, of City of Hope National Medical Center in Duarte, Calif., has won the Medal of Honor in Cancer Control. This award honors individuals who have made strides in public health, public communication, or public policy that have had an impact on cancer control.

Dr. Bernstein won the award for her work linking physical activity to a reduced risk of breast cancer. She is currently investigating links between hormone exposures, physical activity, obesity, and cancer, as well as examining how breast cancer impacts patients’ lives after treatment.

Ching-Hon Pui, MD, of St. Jude Children’s Research Hospital in Memphis, Tenn., has won the Medal of Honor in Clinical Research. This award honors researchers whose work has significantly improved cancer patients’ outcomes.

Dr. Pui won the award for his work in childhood acute lymphoblastic leukemia. Dr. Pui’s work has led to increased global treatment access, improved survival rates, and better quality of life for patients with childhood acute lymphoblastic leukemia.

[email protected]

In this edition of “Applying research to practice,” I highlight I-SPY2 and other studies of pembrolizumab plus chemotherapy in breast cancer patients.

Pathologic complete response (pCR) rates up to 60% were reported for patients with high-risk, stage II/III breast cancer who received pembrolizumab plus standard neoadjuvant chemotherapy (NAC) in I-SPY2, an ongoing platform trial designed to screen multiple agents and pinpoint those with a high probability of success (JAMA Oncol. 2020 Feb 13. doi: 10.1001/jamaoncol.2019.6650).

The addition of pembrolizumab to NAC doubled pCR rates in all three biomarker signatures studied, including ERBB2 (HER2)-negative, hormone receptor (HR)-positive/ERBB2-negative, and triple-negative breast cancer (TNBC).

As a result, pembrolizumab “graduated” from I-SPY2, with a more than 99% predictive probability that the pembrolizumab-plus-NAC approach would be superior to NAC alone in a phase 3 trial. In the HR-positive/ERBB2-negative signature, pembrolizumab is the first agent to graduate among the 10 agents studied since I-SPY2 opened in 2010.

The control arm in I-SPY2 had 181 patients randomized to standard NAC (paclitaxel followed by doxorubicin plus cyclophosphamide). The pembrolizumab arm included 69 patients who received the same NAC regimen plus pembrolizumab, given concurrently with paclitaxel.

The estimated pCR rates in all ERBB2-negative patients were 44% in the pembrolizumab arm and 17% in the control arm. Among the 40 HR-positive/ERBB2-negative patients, the estimated pCR rates were 30% and 13%, respectively. In the 29 TNBC patients, the estimated pCR rates were 60% and 22%, respectively.

Extensive residual cancer burden was less often seen in the pembrolizumab-treated patients than in the comparison group. At a median follow-up of 2.8 years in the pembrolizumab arm and 3.5 years in the NAC arm, 3-year event-free survival was similar between the arms. However, the investigators cautioned against drawing conclusions from this exploratory analysis in a small number of patients. Testifying to the importance of the primary endpoint of pCR rate, patients who achieved pCR had excellent outcomes regardless of their assigned study arms.

Immune-related adverse events in the pembrolizumab-treated patients were generally grade 1 or 2 and were managed with dose interruption or corticosteroid therapy. Most commonly seen was thyroid dysfunction in 13% of patients, as in previously published reports. Adrenal insufficiency occurred more often than expected (8.7%), for unclear reasons, with five of the six reported cases occurring more than 30 days after the last dose of pembrolizumab.

The bigger picture: Putting I-SPY2 results into context

It is well known that responses to pembrolizumab monotherapy in patients with advanced, refractory breast cancer are infrequent. In contrast, in previously untreated patients with PD-L1 positive TNBC, pembrolizumab monotherapy produced a response rate of 21% in KEYNOTE-086 (Ann Oncol. 2019 Mar 1;30(3):405-11). This response rate is similar to that observed with standard chemotherapy, but responses with pembrolizumab were more durable.

In the phase 3 KEYNOTE-355 trial (NCT02819518), researchers are comparing pembrolizumab plus chemotherapy to placebo plus chemotherapy in patients with previously untreated, stage IV TNBC with high PD-L1 expression. Researchers saw a significant and clinically meaningful improvement in progression-free survival in the pembrolizumab arm, according to a recent announcement from Merck. These results lend credence to the I-SPY2 authors’ hypothesis that immune-targeted agents would show their greatest benefit in early-stage breast cancer patients.

In fact, results from I-SPY2 have been confirmed by results from the phase 3 KEYNOTE-522 trial, which were recently published (N Engl J Med 2020;382:810-21) and presented at the San Antonio Breast Cancer Symposium. I-SPY2 predicted that pembrolizumab would be superior to standard NAC in TNBC patients in a phase 3 trial, and it was.

In KEYNOTE-522, the pCR rate was significantly higher in early-stage TNBC patients who received pembrolizumab plus NAC than in early-stage TNBC patients who received placebo plus NAC. The pCR rate was 64.8% in the pembrolizumab-NAC arm and 51.2% in the placebo–NAC arm (estimated treatment difference, 13.6 percentage points; 95% CI, 5.4 to 21.8; P less than .001).

These results are exciting. Results from I-SPY2 and KEYNOTE-522 whet the appetite for results of KEYNOTE-756, an ongoing trial of pembrolizumab plus NAC in HR-positive/ERBB2-negative patients (NCT03725059). Hopefully, the efficacy and toxicity results of KEYNOTE-756 will be as exciting as the I-SPY2 results predict they will be. Among patients with early stage breast cancer whose tumor characteristics are adverse enough to require NAC, better regimens are needed to attain pCR, a validated surrogate for long-term freedom from recurrence.


Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers as well as expanding clinical trial access to medically underserved populations.

In this edition of “Applying research to practice,” I highlight I-SPY2 and other studies of pembrolizumab plus chemotherapy in breast cancer patients.

Pathologic complete response (pCR) rates up to 60% were reported for patients with high-risk, stage II/III breast cancer who received pembrolizumab plus standard neoadjuvant chemotherapy (NAC) in I-SPY2, an ongoing platform trial designed to screen multiple agents and pinpoint those with a high probability of success (JAMA Oncol. 2020 Feb 13. doi: 10.1001/jamaoncol.2019.6650).

The addition of pembrolizumab to NAC doubled pCR rates in all three biomarker signatures studied, including ERBB2 (HER2)-negative, hormone receptor (HR)-positive/ERBB2-negative, and triple-negative breast cancer (TNBC).

As a result, pembrolizumab “graduated” from I-SPY2, with a more than 99% predictive probability that the pembrolizumab-plus-NAC approach would be superior to NAC alone in a phase 3 trial. In the HR-positive/ERBB2-negative signature, pembrolizumab is the first agent to graduate among the 10 agents studied since I-SPY2 opened in 2010.

The control arm in I-SPY2 had 181 patients randomized to standard NAC (paclitaxel followed by doxorubicin plus cyclophosphamide). The pembrolizumab arm included 69 patients who received the same NAC regimen plus pembrolizumab, given concurrently with paclitaxel.

The estimated pCR rates in all ERBB2-negative patients were 44% in the pembrolizumab arm and 17% in the control arm. Among the 40 HR-positive/ERBB2-negative patients, the estimated pCR rates were 30% and 13%, respectively. In the 29 TNBC patients, the estimated pCR rates were 60% and 22%, respectively.

Extensive residual cancer burden was less often seen in the pembrolizumab-treated patients than in the comparison group. At a median follow-up of 2.8 years in the pembrolizumab arm and 3.5 years in the NAC arm, 3-year event-free survival was similar between the arms. However, the investigators cautioned against drawing conclusions from this exploratory analysis in a small number of patients. Testifying to the importance of the primary endpoint of pCR rate, patients who achieved pCR had excellent outcomes regardless of their assigned study arms.

Immune-related adverse events in the pembrolizumab-treated patients were generally grade 1 or 2 and were managed with dose interruption or corticosteroid therapy. Most commonly seen was thyroid dysfunction in 13% of patients, as in previously published reports. Adrenal insufficiency occurred more often than expected (8.7%), for unclear reasons, with five of the six reported cases occurring more than 30 days after the last dose of pembrolizumab.

The bigger picture: Putting I-SPY2 results into context

It is well known that responses to pembrolizumab monotherapy in patients with advanced, refractory breast cancer are infrequent. In contrast, in previously untreated patients with PD-L1 positive TNBC, pembrolizumab monotherapy produced a response rate of 21% in KEYNOTE-086 (Ann Oncol. 2019 Mar 1;30(3):405-11). This response rate is similar to that observed with standard chemotherapy, but responses with pembrolizumab were more durable.

In the phase 3 KEYNOTE-355 trial (NCT02819518), researchers are comparing pembrolizumab plus chemotherapy to placebo plus chemotherapy in patients with previously untreated, stage IV TNBC with high PD-L1 expression. Researchers saw a significant and clinically meaningful improvement in progression-free survival in the pembrolizumab arm, according to a recent announcement from Merck. These results lend credence to the I-SPY2 authors’ hypothesis that immune-targeted agents would show their greatest benefit in early-stage breast cancer patients.

In fact, results from I-SPY2 have been confirmed by results from the phase 3 KEYNOTE-522 trial, which were recently published (N Engl J Med 2020;382:810-21) and presented at the San Antonio Breast Cancer Symposium. I-SPY2 predicted that pembrolizumab would be superior to standard NAC in TNBC patients in a phase 3 trial, and it was.

In KEYNOTE-522, the pCR rate was significantly higher in early-stage TNBC patients who received pembrolizumab plus NAC than in early-stage TNBC patients who received placebo plus NAC. The pCR rate was 64.8% in the pembrolizumab-NAC arm and 51.2% in the placebo–NAC arm (estimated treatment difference, 13.6 percentage points; 95% CI, 5.4 to 21.8; P less than .001).

These results are exciting. Results from I-SPY2 and KEYNOTE-522 whet the appetite for results of KEYNOTE-756, an ongoing trial of pembrolizumab plus NAC in HR-positive/ERBB2-negative patients (NCT03725059). Hopefully, the efficacy and toxicity results of KEYNOTE-756 will be as exciting as the I-SPY2 results predict they will be. Among patients with early stage breast cancer whose tumor characteristics are adverse enough to require NAC, better regimens are needed to attain pCR, a validated surrogate for long-term freedom from recurrence.


Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers as well as expanding clinical trial access to medically underserved populations.

In this edition of “Applying research to practice,” I highlight I-SPY2 and other studies of pembrolizumab plus chemotherapy in breast cancer patients.

Pathologic complete response (pCR) rates up to 60% were reported for patients with high-risk, stage II/III breast cancer who received pembrolizumab plus standard neoadjuvant chemotherapy (NAC) in I-SPY2, an ongoing platform trial designed to screen multiple agents and pinpoint those with a high probability of success (JAMA Oncol. 2020 Feb 13. doi: 10.1001/jamaoncol.2019.6650).

The addition of pembrolizumab to NAC doubled pCR rates in all three biomarker signatures studied, including ERBB2 (HER2)-negative, hormone receptor (HR)-positive/ERBB2-negative, and triple-negative breast cancer (TNBC).

As a result, pembrolizumab “graduated” from I-SPY2, with a more than 99% predictive probability that the pembrolizumab-plus-NAC approach would be superior to NAC alone in a phase 3 trial. In the HR-positive/ERBB2-negative signature, pembrolizumab is the first agent to graduate among the 10 agents studied since I-SPY2 opened in 2010.

The control arm in I-SPY2 had 181 patients randomized to standard NAC (paclitaxel followed by doxorubicin plus cyclophosphamide). The pembrolizumab arm included 69 patients who received the same NAC regimen plus pembrolizumab, given concurrently with paclitaxel.

The estimated pCR rates in all ERBB2-negative patients were 44% in the pembrolizumab arm and 17% in the control arm. Among the 40 HR-positive/ERBB2-negative patients, the estimated pCR rates were 30% and 13%, respectively. In the 29 TNBC patients, the estimated pCR rates were 60% and 22%, respectively.

Extensive residual cancer burden was less often seen in the pembrolizumab-treated patients than in the comparison group. At a median follow-up of 2.8 years in the pembrolizumab arm and 3.5 years in the NAC arm, 3-year event-free survival was similar between the arms. However, the investigators cautioned against drawing conclusions from this exploratory analysis in a small number of patients. Testifying to the importance of the primary endpoint of pCR rate, patients who achieved pCR had excellent outcomes regardless of their assigned study arms.

Immune-related adverse events in the pembrolizumab-treated patients were generally grade 1 or 2 and were managed with dose interruption or corticosteroid therapy. Most commonly seen was thyroid dysfunction in 13% of patients, as in previously published reports. Adrenal insufficiency occurred more often than expected (8.7%), for unclear reasons, with five of the six reported cases occurring more than 30 days after the last dose of pembrolizumab.

The bigger picture: Putting I-SPY2 results into context

It is well known that responses to pembrolizumab monotherapy in patients with advanced, refractory breast cancer are infrequent. In contrast, in previously untreated patients with PD-L1 positive TNBC, pembrolizumab monotherapy produced a response rate of 21% in KEYNOTE-086 (Ann Oncol. 2019 Mar 1;30(3):405-11). This response rate is similar to that observed with standard chemotherapy, but responses with pembrolizumab were more durable.

In the phase 3 KEYNOTE-355 trial (NCT02819518), researchers are comparing pembrolizumab plus chemotherapy to placebo plus chemotherapy in patients with previously untreated, stage IV TNBC with high PD-L1 expression. Researchers saw a significant and clinically meaningful improvement in progression-free survival in the pembrolizumab arm, according to a recent announcement from Merck. These results lend credence to the I-SPY2 authors’ hypothesis that immune-targeted agents would show their greatest benefit in early-stage breast cancer patients.

In fact, results from I-SPY2 have been confirmed by results from the phase 3 KEYNOTE-522 trial, which were recently published (N Engl J Med 2020;382:810-21) and presented at the San Antonio Breast Cancer Symposium. I-SPY2 predicted that pembrolizumab would be superior to standard NAC in TNBC patients in a phase 3 trial, and it was.

In KEYNOTE-522, the pCR rate was significantly higher in early-stage TNBC patients who received pembrolizumab plus NAC than in early-stage TNBC patients who received placebo plus NAC. The pCR rate was 64.8% in the pembrolizumab-NAC arm and 51.2% in the placebo–NAC arm (estimated treatment difference, 13.6 percentage points; 95% CI, 5.4 to 21.8; P less than .001).

These results are exciting. Results from I-SPY2 and KEYNOTE-522 whet the appetite for results of KEYNOTE-756, an ongoing trial of pembrolizumab plus NAC in HR-positive/ERBB2-negative patients (NCT03725059). Hopefully, the efficacy and toxicity results of KEYNOTE-756 will be as exciting as the I-SPY2 results predict they will be. Among patients with early stage breast cancer whose tumor characteristics are adverse enough to require NAC, better regimens are needed to attain pCR, a validated surrogate for long-term freedom from recurrence.


Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers as well as expanding clinical trial access to medically underserved populations.

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

copyright/Thinkstock

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

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

Study details

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

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

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

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

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

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

Interpreting the results

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

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

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

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

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

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

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

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

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

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

copyright/Thinkstock

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

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

Study details

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

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

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

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

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

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

Interpreting the results

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

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

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

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

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

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

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

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

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

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

copyright/Thinkstock

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

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

Study details

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

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

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

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

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

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

Interpreting the results

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Study Details

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

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

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

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

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

Need for Change?

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

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

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

Milk Is Complex Topic

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

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

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

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

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

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

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

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

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

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

Drinking Milk, or Some Related Factor?

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

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

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

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

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

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

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

This article first appeared on Medscape.com.

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

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

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

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

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

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

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

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

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

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

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

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

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

Study Details

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

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

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

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

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

Need for Change?

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

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

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

Milk Is Complex Topic

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

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

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

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

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

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

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

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

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

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

Drinking Milk, or Some Related Factor?

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

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

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

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

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

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

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

This article first appeared on Medscape.com.

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

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

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

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

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

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

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

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

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

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

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

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

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

Study Details

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

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

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

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

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

Need for Change?

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

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

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

Milk Is Complex Topic

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

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

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

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

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

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

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

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

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

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

Drinking Milk, or Some Related Factor?

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

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

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

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

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

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

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

This article first appeared on Medscape.com.

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

Monkeybusinessimages/Thinkstock

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

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

Their article was published online February 20 in BMC Cancer.

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

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

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

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

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

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

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

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

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

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

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

Survey Details

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

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

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

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

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

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

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

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

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

The authors have disclosed no relevant financial relationships.
 

This article first appeared on Medscape.com.

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

Monkeybusinessimages/Thinkstock

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

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

Their article was published online February 20 in BMC Cancer.

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

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

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

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

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

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

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

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

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

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

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

Survey Details

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

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

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

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

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

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

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

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

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

The authors have disclosed no relevant financial relationships.
 

This article first appeared on Medscape.com.

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

Monkeybusinessimages/Thinkstock

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

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

Their article was published online February 20 in BMC Cancer.

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

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

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

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

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

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

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

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

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

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

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

Survey Details

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

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

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

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

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

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

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

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

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

The authors have disclosed no relevant financial relationships.
 

This article first appeared on Medscape.com.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

[email protected]

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

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

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

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

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

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

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

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

[email protected]

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

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

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

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

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

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

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

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

[email protected]

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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