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Tucatinib-Trastuzumab Benefit ‘Remarkable’ in HER2-positive mCRC
Only about 3% to 5% of patients with metastatic colorectal cancer have tumors that are positive for human epidermal growth factor receptor 2 (HER2), and until recently there was no treatment approved by the US Food and Drug Administration (FDA) for this subset of patients.
That all changed, in January of 2023. At that time, the FDA granted accelerated approval to tucatinib (Tukysa) in combination with trastuzumab for RAS wild-type HER2-positive unresectable or metastatic colorectal cancer that has progressed following fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy.
The combination was the first FDA-approved treatment for this patient population.
The only other FDA-approved therapy for metastatic HER2-positive CRC is the antibody-drug conjugate trastuzumab deruxtecan (Enhertu). That drug received accelerated approval from the FDA for metastatic HER2-positive CRC for which no other suitable therapeutic option exists, on April 5, 2024. This FDA action represented an expansion of the drug’s earlier approvals for treating several cancer types, including certain patients with unresectable or metastatic HER2-positive breast cancer and adults with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma who had received a prior trastuzumab-based regimen.
Drug Combo’s Use With Capecitabine in Breast Cancer
Tucatinib is a potent oral tyrosine kinase inhibitor (TKI) that has been shown to be highly selective for HER2. Prior to approval of the colorectal cancer indication, tucatinib had received FDA approval (in April 2020) in combination with trastuzumab and capecitabine for the treatment of patients with advanced unresectable or metastatic HER2-positive breast cancer, including patients with brain metastases, who had received one or more prior anti-HER2-based regimens in the metastatic setting.
In these patients the combination was associated with significant improvements in both progression-free survival (PFS) and overall survival compared with trastuzumab and capecitabine.
Approval for the colorectal cancer indication was based on results of the phase 2 MOUNTAINEER trial, which were published in The Lancet Oncology.
Real-World Setting
Clinical experience with the combination in a real-world setting is still limited due to the relatively uncommon RAS wild-type HER2-positive CRC subtype, so most of what’s known about the efficacy and safety of tucatinib plus trastuzumab comes from clinical trials. But oncologists interviewed for this article emphasized that the tucatinib-trastuzumab combination nonetheless represents a major breakthrough.
“The population of RAS wild-type HER2-positive is small in colorectal cancer, but the benefit of this treatment is really remarkable. With this combination therapy there was a 38% response rate, and there was a very respectable duration of response. So the population is small, but the benefit of the treatment is by no means small,” said Afsaneh Barzi, MD, PhD, a medical oncologist specializing in gastrointestinal cancers at City of Hope in Duarte, California.
Another medical oncologist interviewed for this piece, who treats patients with HER2-positive metastatic CRC, said that the performance of tucatinib in the real-world setting is in keeping with the efficacy seen in clinical trials.
“There is a group of patients who have a very good response to HER2 [targeted] therapy. Often these are patients who have higher degrees of HER2 amplification, and they do not have concomitant other mutations that activate the pathway, such as RAS mutations,” said Kanwal PS Raghav, MD, MBBS, from the University of Texas MD Anderson Cancer Center in Houston.
Why It Works
In an interview, MOUNTAINEER coinvestigator Tanios S. Bekaii-Saab, MD, from the Mayo Clinic Comprehensive Cancer Center in Phoenix, Arizona, explained why dual HER2 blockade with tucatinib and trastuzumab is an important breakthrough for this population.
“HER2 as a target was already well established in breast cancer and in gastric cancer. In colon cancer we had signals [of anti-HER2 efficacy] but these signals were primarily with dual targeted therapy,” he said.
“What’s unique about tucatinib versus neratinib [Nerlynx], lapatinib [Tykerb] and some of the others is that this is a highly selective tyrosine kinase inhibitor, meaning it is potent just against HER2 and has limited activity against other receptors, classically EGFR, which also goes by the name of HER1,” said MOUNTAINEER trial chair John H. Strickler, MD, of Duke Cancer Center in Durham, North Carolina.
“The reason why that’s valuable is that when you inhibit other receptors like HER1 or EGFR, you can cause significant skin rash and other symptoms that can limit tolerability, which limits your ability to give the full dose. With tucatinib you can more completely inhibit HER2 with fewer side effects,” Dr. Strickler said in an interview.
Dr. Raghav noted that the primary adverse events of therapy with tucatinib have been diarrhea and fatigue, and other common side effects include abdominal pain, fever, nausea, rash, and infusion reactions.
Barriers to Treatment
Dr. Barzi pointed out that in the day-to-day practice setting there are two potential barriers to treatment with tucatinib and trastuzumab for patients with HER2-positive colorectal cancer, hurdles that they would not encounter if they were enrolled in clinical trials.
The first barrier is the requirement for HER2 testing, either through immunohistochemistry or fluorescence in situ hybridization.
“The adoption of HER2 testing in colorectal cancer lags behind other molecular testing, such as testing for KRAS or BRAF, so the provider needs to be aware that HER2 positivity is a possibility,” she said.
The second and more difficult-to-surmount barrier is imposed by the healthcare system. Although the combination is included in National Comprehensive Cancer Network guidelines and, therefore, should not be subject to restrictions or denials by insurers, “the challenge is that this is an oral and IV drug combination,” Dr. Barzi said.
While patients in real-world settings receive intravenous drugs such as trastuzumab in treatment centers, the oral drug component, tucatinib, is dispensed by pharmacies, and patients are often required to shell out high copays for such agents.
Dr. Barzi cited as an example the case of one of her patients who was receiving an oral agent — not tucatinib — for treatment of a different type of colorectal cancer.
“He has very good insurance, and after insurance his out-of-pocket cost on a monthly basis to obtain the drug is $275,” she said.
What’s Next
In colorectal cancer the combination of tucatinib and trastuzumab is approved only in the metastatic setting, but it is also being explored as a first-line therapy in combination with the mFOLFOX6 regimen (5-Fluorouracil, leucovorin, and oxaliplatin) in the MOUNTAINEER-03 trial, which is currently recruiting.
MOUNTAINEER was sponsored by Seagen and Merck. Dr. Strickler reported support from Seagen for the Lancet Oncology manuscript; institutional grants, consulting fees, and travel support from Seagen, and similar relationships with other companies. Dr. Bekaii-Saab reported institutional research and consulting fees from various companies, including Merck, personal consulting fees from various companies, and independent monitoring board/scientific advisory board activities. Dr. Raghav disclosed honoraria and an advisory/consulting role for Seagen and others. Dr. Barzi reported no relevant conflicts of interest.
Only about 3% to 5% of patients with metastatic colorectal cancer have tumors that are positive for human epidermal growth factor receptor 2 (HER2), and until recently there was no treatment approved by the US Food and Drug Administration (FDA) for this subset of patients.
That all changed, in January of 2023. At that time, the FDA granted accelerated approval to tucatinib (Tukysa) in combination with trastuzumab for RAS wild-type HER2-positive unresectable or metastatic colorectal cancer that has progressed following fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy.
The combination was the first FDA-approved treatment for this patient population.
The only other FDA-approved therapy for metastatic HER2-positive CRC is the antibody-drug conjugate trastuzumab deruxtecan (Enhertu). That drug received accelerated approval from the FDA for metastatic HER2-positive CRC for which no other suitable therapeutic option exists, on April 5, 2024. This FDA action represented an expansion of the drug’s earlier approvals for treating several cancer types, including certain patients with unresectable or metastatic HER2-positive breast cancer and adults with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma who had received a prior trastuzumab-based regimen.
Drug Combo’s Use With Capecitabine in Breast Cancer
Tucatinib is a potent oral tyrosine kinase inhibitor (TKI) that has been shown to be highly selective for HER2. Prior to approval of the colorectal cancer indication, tucatinib had received FDA approval (in April 2020) in combination with trastuzumab and capecitabine for the treatment of patients with advanced unresectable or metastatic HER2-positive breast cancer, including patients with brain metastases, who had received one or more prior anti-HER2-based regimens in the metastatic setting.
In these patients the combination was associated with significant improvements in both progression-free survival (PFS) and overall survival compared with trastuzumab and capecitabine.
Approval for the colorectal cancer indication was based on results of the phase 2 MOUNTAINEER trial, which were published in The Lancet Oncology.
Real-World Setting
Clinical experience with the combination in a real-world setting is still limited due to the relatively uncommon RAS wild-type HER2-positive CRC subtype, so most of what’s known about the efficacy and safety of tucatinib plus trastuzumab comes from clinical trials. But oncologists interviewed for this article emphasized that the tucatinib-trastuzumab combination nonetheless represents a major breakthrough.
“The population of RAS wild-type HER2-positive is small in colorectal cancer, but the benefit of this treatment is really remarkable. With this combination therapy there was a 38% response rate, and there was a very respectable duration of response. So the population is small, but the benefit of the treatment is by no means small,” said Afsaneh Barzi, MD, PhD, a medical oncologist specializing in gastrointestinal cancers at City of Hope in Duarte, California.
Another medical oncologist interviewed for this piece, who treats patients with HER2-positive metastatic CRC, said that the performance of tucatinib in the real-world setting is in keeping with the efficacy seen in clinical trials.
“There is a group of patients who have a very good response to HER2 [targeted] therapy. Often these are patients who have higher degrees of HER2 amplification, and they do not have concomitant other mutations that activate the pathway, such as RAS mutations,” said Kanwal PS Raghav, MD, MBBS, from the University of Texas MD Anderson Cancer Center in Houston.
Why It Works
In an interview, MOUNTAINEER coinvestigator Tanios S. Bekaii-Saab, MD, from the Mayo Clinic Comprehensive Cancer Center in Phoenix, Arizona, explained why dual HER2 blockade with tucatinib and trastuzumab is an important breakthrough for this population.
“HER2 as a target was already well established in breast cancer and in gastric cancer. In colon cancer we had signals [of anti-HER2 efficacy] but these signals were primarily with dual targeted therapy,” he said.
“What’s unique about tucatinib versus neratinib [Nerlynx], lapatinib [Tykerb] and some of the others is that this is a highly selective tyrosine kinase inhibitor, meaning it is potent just against HER2 and has limited activity against other receptors, classically EGFR, which also goes by the name of HER1,” said MOUNTAINEER trial chair John H. Strickler, MD, of Duke Cancer Center in Durham, North Carolina.
“The reason why that’s valuable is that when you inhibit other receptors like HER1 or EGFR, you can cause significant skin rash and other symptoms that can limit tolerability, which limits your ability to give the full dose. With tucatinib you can more completely inhibit HER2 with fewer side effects,” Dr. Strickler said in an interview.
Dr. Raghav noted that the primary adverse events of therapy with tucatinib have been diarrhea and fatigue, and other common side effects include abdominal pain, fever, nausea, rash, and infusion reactions.
Barriers to Treatment
Dr. Barzi pointed out that in the day-to-day practice setting there are two potential barriers to treatment with tucatinib and trastuzumab for patients with HER2-positive colorectal cancer, hurdles that they would not encounter if they were enrolled in clinical trials.
The first barrier is the requirement for HER2 testing, either through immunohistochemistry or fluorescence in situ hybridization.
“The adoption of HER2 testing in colorectal cancer lags behind other molecular testing, such as testing for KRAS or BRAF, so the provider needs to be aware that HER2 positivity is a possibility,” she said.
The second and more difficult-to-surmount barrier is imposed by the healthcare system. Although the combination is included in National Comprehensive Cancer Network guidelines and, therefore, should not be subject to restrictions or denials by insurers, “the challenge is that this is an oral and IV drug combination,” Dr. Barzi said.
While patients in real-world settings receive intravenous drugs such as trastuzumab in treatment centers, the oral drug component, tucatinib, is dispensed by pharmacies, and patients are often required to shell out high copays for such agents.
Dr. Barzi cited as an example the case of one of her patients who was receiving an oral agent — not tucatinib — for treatment of a different type of colorectal cancer.
“He has very good insurance, and after insurance his out-of-pocket cost on a monthly basis to obtain the drug is $275,” she said.
What’s Next
In colorectal cancer the combination of tucatinib and trastuzumab is approved only in the metastatic setting, but it is also being explored as a first-line therapy in combination with the mFOLFOX6 regimen (5-Fluorouracil, leucovorin, and oxaliplatin) in the MOUNTAINEER-03 trial, which is currently recruiting.
MOUNTAINEER was sponsored by Seagen and Merck. Dr. Strickler reported support from Seagen for the Lancet Oncology manuscript; institutional grants, consulting fees, and travel support from Seagen, and similar relationships with other companies. Dr. Bekaii-Saab reported institutional research and consulting fees from various companies, including Merck, personal consulting fees from various companies, and independent monitoring board/scientific advisory board activities. Dr. Raghav disclosed honoraria and an advisory/consulting role for Seagen and others. Dr. Barzi reported no relevant conflicts of interest.
Only about 3% to 5% of patients with metastatic colorectal cancer have tumors that are positive for human epidermal growth factor receptor 2 (HER2), and until recently there was no treatment approved by the US Food and Drug Administration (FDA) for this subset of patients.
That all changed, in January of 2023. At that time, the FDA granted accelerated approval to tucatinib (Tukysa) in combination with trastuzumab for RAS wild-type HER2-positive unresectable or metastatic colorectal cancer that has progressed following fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy.
The combination was the first FDA-approved treatment for this patient population.
The only other FDA-approved therapy for metastatic HER2-positive CRC is the antibody-drug conjugate trastuzumab deruxtecan (Enhertu). That drug received accelerated approval from the FDA for metastatic HER2-positive CRC for which no other suitable therapeutic option exists, on April 5, 2024. This FDA action represented an expansion of the drug’s earlier approvals for treating several cancer types, including certain patients with unresectable or metastatic HER2-positive breast cancer and adults with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma who had received a prior trastuzumab-based regimen.
Drug Combo’s Use With Capecitabine in Breast Cancer
Tucatinib is a potent oral tyrosine kinase inhibitor (TKI) that has been shown to be highly selective for HER2. Prior to approval of the colorectal cancer indication, tucatinib had received FDA approval (in April 2020) in combination with trastuzumab and capecitabine for the treatment of patients with advanced unresectable or metastatic HER2-positive breast cancer, including patients with brain metastases, who had received one or more prior anti-HER2-based regimens in the metastatic setting.
In these patients the combination was associated with significant improvements in both progression-free survival (PFS) and overall survival compared with trastuzumab and capecitabine.
Approval for the colorectal cancer indication was based on results of the phase 2 MOUNTAINEER trial, which were published in The Lancet Oncology.
Real-World Setting
Clinical experience with the combination in a real-world setting is still limited due to the relatively uncommon RAS wild-type HER2-positive CRC subtype, so most of what’s known about the efficacy and safety of tucatinib plus trastuzumab comes from clinical trials. But oncologists interviewed for this article emphasized that the tucatinib-trastuzumab combination nonetheless represents a major breakthrough.
“The population of RAS wild-type HER2-positive is small in colorectal cancer, but the benefit of this treatment is really remarkable. With this combination therapy there was a 38% response rate, and there was a very respectable duration of response. So the population is small, but the benefit of the treatment is by no means small,” said Afsaneh Barzi, MD, PhD, a medical oncologist specializing in gastrointestinal cancers at City of Hope in Duarte, California.
Another medical oncologist interviewed for this piece, who treats patients with HER2-positive metastatic CRC, said that the performance of tucatinib in the real-world setting is in keeping with the efficacy seen in clinical trials.
“There is a group of patients who have a very good response to HER2 [targeted] therapy. Often these are patients who have higher degrees of HER2 amplification, and they do not have concomitant other mutations that activate the pathway, such as RAS mutations,” said Kanwal PS Raghav, MD, MBBS, from the University of Texas MD Anderson Cancer Center in Houston.
Why It Works
In an interview, MOUNTAINEER coinvestigator Tanios S. Bekaii-Saab, MD, from the Mayo Clinic Comprehensive Cancer Center in Phoenix, Arizona, explained why dual HER2 blockade with tucatinib and trastuzumab is an important breakthrough for this population.
“HER2 as a target was already well established in breast cancer and in gastric cancer. In colon cancer we had signals [of anti-HER2 efficacy] but these signals were primarily with dual targeted therapy,” he said.
“What’s unique about tucatinib versus neratinib [Nerlynx], lapatinib [Tykerb] and some of the others is that this is a highly selective tyrosine kinase inhibitor, meaning it is potent just against HER2 and has limited activity against other receptors, classically EGFR, which also goes by the name of HER1,” said MOUNTAINEER trial chair John H. Strickler, MD, of Duke Cancer Center in Durham, North Carolina.
“The reason why that’s valuable is that when you inhibit other receptors like HER1 or EGFR, you can cause significant skin rash and other symptoms that can limit tolerability, which limits your ability to give the full dose. With tucatinib you can more completely inhibit HER2 with fewer side effects,” Dr. Strickler said in an interview.
Dr. Raghav noted that the primary adverse events of therapy with tucatinib have been diarrhea and fatigue, and other common side effects include abdominal pain, fever, nausea, rash, and infusion reactions.
Barriers to Treatment
Dr. Barzi pointed out that in the day-to-day practice setting there are two potential barriers to treatment with tucatinib and trastuzumab for patients with HER2-positive colorectal cancer, hurdles that they would not encounter if they were enrolled in clinical trials.
The first barrier is the requirement for HER2 testing, either through immunohistochemistry or fluorescence in situ hybridization.
“The adoption of HER2 testing in colorectal cancer lags behind other molecular testing, such as testing for KRAS or BRAF, so the provider needs to be aware that HER2 positivity is a possibility,” she said.
The second and more difficult-to-surmount barrier is imposed by the healthcare system. Although the combination is included in National Comprehensive Cancer Network guidelines and, therefore, should not be subject to restrictions or denials by insurers, “the challenge is that this is an oral and IV drug combination,” Dr. Barzi said.
While patients in real-world settings receive intravenous drugs such as trastuzumab in treatment centers, the oral drug component, tucatinib, is dispensed by pharmacies, and patients are often required to shell out high copays for such agents.
Dr. Barzi cited as an example the case of one of her patients who was receiving an oral agent — not tucatinib — for treatment of a different type of colorectal cancer.
“He has very good insurance, and after insurance his out-of-pocket cost on a monthly basis to obtain the drug is $275,” she said.
What’s Next
In colorectal cancer the combination of tucatinib and trastuzumab is approved only in the metastatic setting, but it is also being explored as a first-line therapy in combination with the mFOLFOX6 regimen (5-Fluorouracil, leucovorin, and oxaliplatin) in the MOUNTAINEER-03 trial, which is currently recruiting.
MOUNTAINEER was sponsored by Seagen and Merck. Dr. Strickler reported support from Seagen for the Lancet Oncology manuscript; institutional grants, consulting fees, and travel support from Seagen, and similar relationships with other companies. Dr. Bekaii-Saab reported institutional research and consulting fees from various companies, including Merck, personal consulting fees from various companies, and independent monitoring board/scientific advisory board activities. Dr. Raghav disclosed honoraria and an advisory/consulting role for Seagen and others. Dr. Barzi reported no relevant conflicts of interest.
Improved Survival With Everolimus + Endocrine Therapy in HR+/HER2− Advanced BC
Key clinical point: Everolimus plus endocrine therapy (ET) led to promising survival outcomes in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−) advanced breast cancer (BC) who progressed on a CDK4/6 inhibitor.
Major finding: Everolimus + ET led to a median progression-free survival (mPFS) of 6 months (95% CI 5.3-7.8 months), with longer mPFS observed in patients previously treated with CDK4/6 inhibitors for >18 months (8.7 months; 95% CI 6.6-11.3 months), patients without visceral metastasis (8.0 months; 95% CI 5.8-10.5 months), and chemotherapy-naive patients (7.2 months; 95% CI 5.9-8.4 months).
Study details: This retrospective observational study included 161 patients with HR+/HER2− advanced BC who were previously treated with CDK4/6 inhibitors and received everolimus + ET.
Disclosures: This study did not receive any funding. Several authors declared receiving honoraria, research grants, or travel support from or having other ties with various sources.
Source: Sánchez-Bayona R, Lopez de Sa A, Jerez Gilarranz Y, et al. Everolimus plus endocrine therapy beyond CDK4/6 inhibitors progression for HR+ /HER2− advanced breast cancer: A real-world evidence cohort. Breast Cancer Res Treat. 2024 (May 4). doi: 10.1007/s10549-024-07324-8 Source
Key clinical point: Everolimus plus endocrine therapy (ET) led to promising survival outcomes in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−) advanced breast cancer (BC) who progressed on a CDK4/6 inhibitor.
Major finding: Everolimus + ET led to a median progression-free survival (mPFS) of 6 months (95% CI 5.3-7.8 months), with longer mPFS observed in patients previously treated with CDK4/6 inhibitors for >18 months (8.7 months; 95% CI 6.6-11.3 months), patients without visceral metastasis (8.0 months; 95% CI 5.8-10.5 months), and chemotherapy-naive patients (7.2 months; 95% CI 5.9-8.4 months).
Study details: This retrospective observational study included 161 patients with HR+/HER2− advanced BC who were previously treated with CDK4/6 inhibitors and received everolimus + ET.
Disclosures: This study did not receive any funding. Several authors declared receiving honoraria, research grants, or travel support from or having other ties with various sources.
Source: Sánchez-Bayona R, Lopez de Sa A, Jerez Gilarranz Y, et al. Everolimus plus endocrine therapy beyond CDK4/6 inhibitors progression for HR+ /HER2− advanced breast cancer: A real-world evidence cohort. Breast Cancer Res Treat. 2024 (May 4). doi: 10.1007/s10549-024-07324-8 Source
Key clinical point: Everolimus plus endocrine therapy (ET) led to promising survival outcomes in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−) advanced breast cancer (BC) who progressed on a CDK4/6 inhibitor.
Major finding: Everolimus + ET led to a median progression-free survival (mPFS) of 6 months (95% CI 5.3-7.8 months), with longer mPFS observed in patients previously treated with CDK4/6 inhibitors for >18 months (8.7 months; 95% CI 6.6-11.3 months), patients without visceral metastasis (8.0 months; 95% CI 5.8-10.5 months), and chemotherapy-naive patients (7.2 months; 95% CI 5.9-8.4 months).
Study details: This retrospective observational study included 161 patients with HR+/HER2− advanced BC who were previously treated with CDK4/6 inhibitors and received everolimus + ET.
Disclosures: This study did not receive any funding. Several authors declared receiving honoraria, research grants, or travel support from or having other ties with various sources.
Source: Sánchez-Bayona R, Lopez de Sa A, Jerez Gilarranz Y, et al. Everolimus plus endocrine therapy beyond CDK4/6 inhibitors progression for HR+ /HER2− advanced breast cancer: A real-world evidence cohort. Breast Cancer Res Treat. 2024 (May 4). doi: 10.1007/s10549-024-07324-8 Source
Anthracycline and Trastuzumab Tied to Long-Term CVD Risk in BC Survivors
Key clinical point: Chemotherapy with anthracycline or trastuzumab increased the risk for cardiovascular diseases (CVD) in breast cancer (BC) survivors, with the risk persisting beyond 10 years after BC diagnosis and being high in women age < 65 years.
Major finding: Anthracycline or trastuzumab vs no chemotherapy was associated with a 53% higher risk for incident CVD (adjusted hazard ratio [aHR] 1.53; 95% CI 1.31-1.79), particularly in women age < 65 years (aHR 1.70; 95% CI ≥1.19 to ≤2.45). The risk for CVD was seen beyond 5 years after BC diagnosis (aHR5-<10 years 1.85; 95% CI 1.44-2.39; aHR10+ years 1.83; 95% CI 1.34-2.49).
Study details: This retrospective cohort study included 10,211 female BC survivors who received anthracycline or trastuzumab (n = 2712), other chemotherapies (n = 1185), or no chemotherapy (n = 6314), with a median follow-up period of 5.79 years.
Disclosures: This study was supported in part by the Intramural Research Program of the US National Cancer Institute. The authors declared no conflicts of interest.
Source: Vo JB, Ramin C, Veiga LHS, et al. Long-term cardiovascular disease risk after anthracycline and trastuzumab treatments in U.S. breast cancer survivors. J Natl Cancer Inst. 2024 (May 8). doi: 10.1093/jnci/djae107 Source
Key clinical point: Chemotherapy with anthracycline or trastuzumab increased the risk for cardiovascular diseases (CVD) in breast cancer (BC) survivors, with the risk persisting beyond 10 years after BC diagnosis and being high in women age < 65 years.
Major finding: Anthracycline or trastuzumab vs no chemotherapy was associated with a 53% higher risk for incident CVD (adjusted hazard ratio [aHR] 1.53; 95% CI 1.31-1.79), particularly in women age < 65 years (aHR 1.70; 95% CI ≥1.19 to ≤2.45). The risk for CVD was seen beyond 5 years after BC diagnosis (aHR5-<10 years 1.85; 95% CI 1.44-2.39; aHR10+ years 1.83; 95% CI 1.34-2.49).
Study details: This retrospective cohort study included 10,211 female BC survivors who received anthracycline or trastuzumab (n = 2712), other chemotherapies (n = 1185), or no chemotherapy (n = 6314), with a median follow-up period of 5.79 years.
Disclosures: This study was supported in part by the Intramural Research Program of the US National Cancer Institute. The authors declared no conflicts of interest.
Source: Vo JB, Ramin C, Veiga LHS, et al. Long-term cardiovascular disease risk after anthracycline and trastuzumab treatments in U.S. breast cancer survivors. J Natl Cancer Inst. 2024 (May 8). doi: 10.1093/jnci/djae107 Source
Key clinical point: Chemotherapy with anthracycline or trastuzumab increased the risk for cardiovascular diseases (CVD) in breast cancer (BC) survivors, with the risk persisting beyond 10 years after BC diagnosis and being high in women age < 65 years.
Major finding: Anthracycline or trastuzumab vs no chemotherapy was associated with a 53% higher risk for incident CVD (adjusted hazard ratio [aHR] 1.53; 95% CI 1.31-1.79), particularly in women age < 65 years (aHR 1.70; 95% CI ≥1.19 to ≤2.45). The risk for CVD was seen beyond 5 years after BC diagnosis (aHR5-<10 years 1.85; 95% CI 1.44-2.39; aHR10+ years 1.83; 95% CI 1.34-2.49).
Study details: This retrospective cohort study included 10,211 female BC survivors who received anthracycline or trastuzumab (n = 2712), other chemotherapies (n = 1185), or no chemotherapy (n = 6314), with a median follow-up period of 5.79 years.
Disclosures: This study was supported in part by the Intramural Research Program of the US National Cancer Institute. The authors declared no conflicts of interest.
Source: Vo JB, Ramin C, Veiga LHS, et al. Long-term cardiovascular disease risk after anthracycline and trastuzumab treatments in U.S. breast cancer survivors. J Natl Cancer Inst. 2024 (May 8). doi: 10.1093/jnci/djae107 Source
Breast-Conserving Surgery Candidates Can Opt for Neoadjuvant Radiochemotherapy
Key clinical point: Neoadjuvant radiation therapy (NART) led to similar survival outcomes as postoperation radiation therapy (PORT) in patients with invasive ductal carcinoma (IDC) who underwent breast-conserving surgery (BCS) and were treated with neoadjuvant chemotherapy.
Major finding: NART vs PORT led to comparable breast cancer-specific survival (BCCS) and overall survival (OS) outcomes (both log-rank P > .05) in patients undergoing BCS or implant-based immediate breast reconstruction. However, NART vs PORT led to significantly lower BCCS (hazard ratio [HR] 1.407; log-rank P = .003) and OS (HR 1.383; log-rank P = .004) outcomes in those undergoing mastectomy.
Study details: This retrospective study included 14,515 women with IDC (age ≤ 80 years) from the Surveillance, Epidemiology, and End Results (SEER) database who were treated with neoadjuvant chemotherapy, of whom 386 and 14,129 patients underwent NART and PORT, respectively.
Disclosures: This study was supported by Shanghai Science and Technology Commission and Fudan University, China. The authors declared no conflicts of interest.
Source: Yuan J, Zhang M, Wang M, et al. Neoadjuvant radiochemotherapy is safe and feasible for breast conserving surgery or immediate reconstruction. Sci Rep. 2024;14:9208 (Apr 22). doi: 10.1038/s41598-024-59961-0 Source
Key clinical point: Neoadjuvant radiation therapy (NART) led to similar survival outcomes as postoperation radiation therapy (PORT) in patients with invasive ductal carcinoma (IDC) who underwent breast-conserving surgery (BCS) and were treated with neoadjuvant chemotherapy.
Major finding: NART vs PORT led to comparable breast cancer-specific survival (BCCS) and overall survival (OS) outcomes (both log-rank P > .05) in patients undergoing BCS or implant-based immediate breast reconstruction. However, NART vs PORT led to significantly lower BCCS (hazard ratio [HR] 1.407; log-rank P = .003) and OS (HR 1.383; log-rank P = .004) outcomes in those undergoing mastectomy.
Study details: This retrospective study included 14,515 women with IDC (age ≤ 80 years) from the Surveillance, Epidemiology, and End Results (SEER) database who were treated with neoadjuvant chemotherapy, of whom 386 and 14,129 patients underwent NART and PORT, respectively.
Disclosures: This study was supported by Shanghai Science and Technology Commission and Fudan University, China. The authors declared no conflicts of interest.
Source: Yuan J, Zhang M, Wang M, et al. Neoadjuvant radiochemotherapy is safe and feasible for breast conserving surgery or immediate reconstruction. Sci Rep. 2024;14:9208 (Apr 22). doi: 10.1038/s41598-024-59961-0 Source
Key clinical point: Neoadjuvant radiation therapy (NART) led to similar survival outcomes as postoperation radiation therapy (PORT) in patients with invasive ductal carcinoma (IDC) who underwent breast-conserving surgery (BCS) and were treated with neoadjuvant chemotherapy.
Major finding: NART vs PORT led to comparable breast cancer-specific survival (BCCS) and overall survival (OS) outcomes (both log-rank P > .05) in patients undergoing BCS or implant-based immediate breast reconstruction. However, NART vs PORT led to significantly lower BCCS (hazard ratio [HR] 1.407; log-rank P = .003) and OS (HR 1.383; log-rank P = .004) outcomes in those undergoing mastectomy.
Study details: This retrospective study included 14,515 women with IDC (age ≤ 80 years) from the Surveillance, Epidemiology, and End Results (SEER) database who were treated with neoadjuvant chemotherapy, of whom 386 and 14,129 patients underwent NART and PORT, respectively.
Disclosures: This study was supported by Shanghai Science and Technology Commission and Fudan University, China. The authors declared no conflicts of interest.
Source: Yuan J, Zhang M, Wang M, et al. Neoadjuvant radiochemotherapy is safe and feasible for breast conserving surgery or immediate reconstruction. Sci Rep. 2024;14:9208 (Apr 22). doi: 10.1038/s41598-024-59961-0 Source
Statin Use Improves Cancer-Specific Survival in Older Women With Breast Cancer
Key clinical point: Use of a statin after breast cancer (BC) diagnosis improved survival in older women (age ≥ 66 years) with localized and regional stage disease, particularly in those with the hormone receptor-positive (HR+) human epidermal growth factor receptor 2-negative (HER2−) subtype.
Major finding: Use vs no use of a statin postdiagnosis was associated with a 15% reduced risk for BC-specific mortality (hazard ratio 0.85; 95% CI 0.75-0.96), with the effect being more pronounced women with HR+/HER2− BC (hazard ratio 0.71; 95% CI 0.57-0.88). There was no significant association between postdiagnosis statin use and the risk for BC recurrence (hazard ratio 1.05; 95% CI 0.91-1.21).
Study details: This retrospective cohort study included women with localized and regional stage BC from the Surveillance, Epidemiology, and End Results (SEER)–Medicare database who were assessed for mortality (n = 38,858) and recurrence (n = 28,522), of whom 8836 and 6475 used a statin postdiagnosis, respectively.
Disclosures: This study was supported by the US National Cancer Institute, National Institutes of Health. The authors declared no conflicts of interest.
Source: Guo H, Malone KE, Heckbert SR, Li CI. Statin use and risks of breast cancer recurrence and mortality. Cancer. 2024 (May 6). doi: 10.1002/cncr.35362 Source
Key clinical point: Use of a statin after breast cancer (BC) diagnosis improved survival in older women (age ≥ 66 years) with localized and regional stage disease, particularly in those with the hormone receptor-positive (HR+) human epidermal growth factor receptor 2-negative (HER2−) subtype.
Major finding: Use vs no use of a statin postdiagnosis was associated with a 15% reduced risk for BC-specific mortality (hazard ratio 0.85; 95% CI 0.75-0.96), with the effect being more pronounced women with HR+/HER2− BC (hazard ratio 0.71; 95% CI 0.57-0.88). There was no significant association between postdiagnosis statin use and the risk for BC recurrence (hazard ratio 1.05; 95% CI 0.91-1.21).
Study details: This retrospective cohort study included women with localized and regional stage BC from the Surveillance, Epidemiology, and End Results (SEER)–Medicare database who were assessed for mortality (n = 38,858) and recurrence (n = 28,522), of whom 8836 and 6475 used a statin postdiagnosis, respectively.
Disclosures: This study was supported by the US National Cancer Institute, National Institutes of Health. The authors declared no conflicts of interest.
Source: Guo H, Malone KE, Heckbert SR, Li CI. Statin use and risks of breast cancer recurrence and mortality. Cancer. 2024 (May 6). doi: 10.1002/cncr.35362 Source
Key clinical point: Use of a statin after breast cancer (BC) diagnosis improved survival in older women (age ≥ 66 years) with localized and regional stage disease, particularly in those with the hormone receptor-positive (HR+) human epidermal growth factor receptor 2-negative (HER2−) subtype.
Major finding: Use vs no use of a statin postdiagnosis was associated with a 15% reduced risk for BC-specific mortality (hazard ratio 0.85; 95% CI 0.75-0.96), with the effect being more pronounced women with HR+/HER2− BC (hazard ratio 0.71; 95% CI 0.57-0.88). There was no significant association between postdiagnosis statin use and the risk for BC recurrence (hazard ratio 1.05; 95% CI 0.91-1.21).
Study details: This retrospective cohort study included women with localized and regional stage BC from the Surveillance, Epidemiology, and End Results (SEER)–Medicare database who were assessed for mortality (n = 38,858) and recurrence (n = 28,522), of whom 8836 and 6475 used a statin postdiagnosis, respectively.
Disclosures: This study was supported by the US National Cancer Institute, National Institutes of Health. The authors declared no conflicts of interest.
Source: Guo H, Malone KE, Heckbert SR, Li CI. Statin use and risks of breast cancer recurrence and mortality. Cancer. 2024 (May 6). doi: 10.1002/cncr.35362 Source
SLNB Not Required Before Neoadjuvant Chemotherapy in Node-Negative Breast Cancer
Key clinical point: Sentinel lymph node biopsy (SLNB) performed before vs after neoadjuvant chemotherapy (NACT) showed a higher axillary lymph node dissection rate and no overall survival (OS) benefits in patients with clinically lymph node-negative (cN0) breast cancer (BC).
Major finding: The axillary lymph node dissection rate was significantly higher for SLNB performed before vs after NACT (29.9% vs 7.4%; P < .001; odds ratio 5.35; P = .002). Moreover, the 4-year overall survival rate was significantly compromised when SLNB was performed before vs after NACT (88.4% vs 95.7%; hazard ratio 0.21; P = .009).
Study details: This retrospective observational study included 310 patients with cN0 BC, of whom 107 and 203 patients underwent SLNB before and after NACT, respectively.
Disclosures: This study did not receive any specific funding except Open Access funding from Springer Nature. The authors declared no financial conflicts of interest. Two authors declared non-financial ties with various sources.
Source: Fernandez-Gonzalez S, Falo C, Pla MJ, et al. Sentinel lymph node biopsy before and after neoadjuvant chemotherapy in cN0 breast cancer patients: Impact on axillary morbidity and survival—A propensity score cohort study. Breast Cancer Res Treat. 2024 (Apr 18). doi: 10.1007/s10549-024-07274-1 Source
Key clinical point: Sentinel lymph node biopsy (SLNB) performed before vs after neoadjuvant chemotherapy (NACT) showed a higher axillary lymph node dissection rate and no overall survival (OS) benefits in patients with clinically lymph node-negative (cN0) breast cancer (BC).
Major finding: The axillary lymph node dissection rate was significantly higher for SLNB performed before vs after NACT (29.9% vs 7.4%; P < .001; odds ratio 5.35; P = .002). Moreover, the 4-year overall survival rate was significantly compromised when SLNB was performed before vs after NACT (88.4% vs 95.7%; hazard ratio 0.21; P = .009).
Study details: This retrospective observational study included 310 patients with cN0 BC, of whom 107 and 203 patients underwent SLNB before and after NACT, respectively.
Disclosures: This study did not receive any specific funding except Open Access funding from Springer Nature. The authors declared no financial conflicts of interest. Two authors declared non-financial ties with various sources.
Source: Fernandez-Gonzalez S, Falo C, Pla MJ, et al. Sentinel lymph node biopsy before and after neoadjuvant chemotherapy in cN0 breast cancer patients: Impact on axillary morbidity and survival—A propensity score cohort study. Breast Cancer Res Treat. 2024 (Apr 18). doi: 10.1007/s10549-024-07274-1 Source
Key clinical point: Sentinel lymph node biopsy (SLNB) performed before vs after neoadjuvant chemotherapy (NACT) showed a higher axillary lymph node dissection rate and no overall survival (OS) benefits in patients with clinically lymph node-negative (cN0) breast cancer (BC).
Major finding: The axillary lymph node dissection rate was significantly higher for SLNB performed before vs after NACT (29.9% vs 7.4%; P < .001; odds ratio 5.35; P = .002). Moreover, the 4-year overall survival rate was significantly compromised when SLNB was performed before vs after NACT (88.4% vs 95.7%; hazard ratio 0.21; P = .009).
Study details: This retrospective observational study included 310 patients with cN0 BC, of whom 107 and 203 patients underwent SLNB before and after NACT, respectively.
Disclosures: This study did not receive any specific funding except Open Access funding from Springer Nature. The authors declared no financial conflicts of interest. Two authors declared non-financial ties with various sources.
Source: Fernandez-Gonzalez S, Falo C, Pla MJ, et al. Sentinel lymph node biopsy before and after neoadjuvant chemotherapy in cN0 breast cancer patients: Impact on axillary morbidity and survival—A propensity score cohort study. Breast Cancer Res Treat. 2024 (Apr 18). doi: 10.1007/s10549-024-07274-1 Source
Trastuzumab Deruxtecan Bests Trastuzumab Emtansine in HER2+ BC With or Without Brain Metastases
Key clinical point: Trastuzumab deruxtecan demonstrated superior efficacy over trastuzumab emtansine as second-line treatment in patients with human epidermal growth factor receptor 2-positive (HER2+) breast cancer (BC) with or without brain metastases.
Major finding: Trastuzumab deruxtecan led to significantly longer median progression-free survival (15.0 vs 3.0 months; hazard ratio 0.25; 95% CI 0.13-0.45) and higher systemic (67.4% vs 20.5%) and intracranial (65.7% vs 34.3%) objective response rates than trastuzumab emtansine in patients with brain metastases. Outcomes were similar in patients without brain metastases.
Study details: This exploratory analysis of the phase 3 DESTINY-Breast03 trial included 524 patients with HER2+ metastatic BC with or without brain metastases who were randomly assigned to receive trastuzumab deruxtecan or trastuzumab emtansine after their disease progressed with trastuzumab and taxane treatment.
Disclosures: This study was supported by Daiichi Sankyo and AstraZeneca. Six authors declared being current or former employees or holding stock or stock options of Daiichi Sankyo or AstraZeneca. Several authors declared having ties to various sources, including Daiichi Sankyo and AstraZeneca.
Source: Hurvitz SA, Kim SB, Chung WP, et al. Trastuzumab deruxtecan versus trastuzumab emtansine in HER2-positive metastatic breast cancer patients with brain metastases from the randomized DESTINY-Breast03 trial. ESMO Open. 2024;109294 (Apr 24). doi: 10.1016/j.esmoop.2024.102924 Source
Key clinical point: Trastuzumab deruxtecan demonstrated superior efficacy over trastuzumab emtansine as second-line treatment in patients with human epidermal growth factor receptor 2-positive (HER2+) breast cancer (BC) with or without brain metastases.
Major finding: Trastuzumab deruxtecan led to significantly longer median progression-free survival (15.0 vs 3.0 months; hazard ratio 0.25; 95% CI 0.13-0.45) and higher systemic (67.4% vs 20.5%) and intracranial (65.7% vs 34.3%) objective response rates than trastuzumab emtansine in patients with brain metastases. Outcomes were similar in patients without brain metastases.
Study details: This exploratory analysis of the phase 3 DESTINY-Breast03 trial included 524 patients with HER2+ metastatic BC with or without brain metastases who were randomly assigned to receive trastuzumab deruxtecan or trastuzumab emtansine after their disease progressed with trastuzumab and taxane treatment.
Disclosures: This study was supported by Daiichi Sankyo and AstraZeneca. Six authors declared being current or former employees or holding stock or stock options of Daiichi Sankyo or AstraZeneca. Several authors declared having ties to various sources, including Daiichi Sankyo and AstraZeneca.
Source: Hurvitz SA, Kim SB, Chung WP, et al. Trastuzumab deruxtecan versus trastuzumab emtansine in HER2-positive metastatic breast cancer patients with brain metastases from the randomized DESTINY-Breast03 trial. ESMO Open. 2024;109294 (Apr 24). doi: 10.1016/j.esmoop.2024.102924 Source
Key clinical point: Trastuzumab deruxtecan demonstrated superior efficacy over trastuzumab emtansine as second-line treatment in patients with human epidermal growth factor receptor 2-positive (HER2+) breast cancer (BC) with or without brain metastases.
Major finding: Trastuzumab deruxtecan led to significantly longer median progression-free survival (15.0 vs 3.0 months; hazard ratio 0.25; 95% CI 0.13-0.45) and higher systemic (67.4% vs 20.5%) and intracranial (65.7% vs 34.3%) objective response rates than trastuzumab emtansine in patients with brain metastases. Outcomes were similar in patients without brain metastases.
Study details: This exploratory analysis of the phase 3 DESTINY-Breast03 trial included 524 patients with HER2+ metastatic BC with or without brain metastases who were randomly assigned to receive trastuzumab deruxtecan or trastuzumab emtansine after their disease progressed with trastuzumab and taxane treatment.
Disclosures: This study was supported by Daiichi Sankyo and AstraZeneca. Six authors declared being current or former employees or holding stock or stock options of Daiichi Sankyo or AstraZeneca. Several authors declared having ties to various sources, including Daiichi Sankyo and AstraZeneca.
Source: Hurvitz SA, Kim SB, Chung WP, et al. Trastuzumab deruxtecan versus trastuzumab emtansine in HER2-positive metastatic breast cancer patients with brain metastases from the randomized DESTINY-Breast03 trial. ESMO Open. 2024;109294 (Apr 24). doi: 10.1016/j.esmoop.2024.102924 Source
Axillary Lymph Node Dissection Can Be Omitted After Nodal Downstaging With Chemotherapy in BC
Key clinical point: Axillary lymph node dissection (ALND) can be omitted in node-positive breast cancer (BC) as only 1% of patients who achieved nodal pathological complete response (pCR) with neoadjuvant chemotherapy reported axillary recurrence (AR) in 5 years.
Major finding: The AR rate was very low at 0.65% (95% CI 0.29%-1.30%) and 1.0% (95% CI 0.49%-2.00%) at 3 years and 5 years, respectively, in patients who omitted ALND and underwent targeted axillary dissection (TAD) or sentinel lymph node biopsy (SLNB). AR rates were comparable in both surgical cohorts at 3 years (P = .55).
Study details: This retrospective cohort study included 1144 patients with node-positive BC who achieved nodal pCR with neoadjuvant chemotherapy, of whom 58.2% and 41.8% underwent SLNB and TAD, respectively.
Disclosures: This study was supported in part by a US National Institutes of Health and US National Cancer Institute Cancer Center support grant. Several authors declared receiving personal fees, grants, or consulting fees from or having other ties with various sources.
Source: Montagna G, Mrdutt MM, Sun SX, et al. Omission of axillary dissection following nodal downstaging with neoadjuvant chemotherapy. JAMA Oncol. 2024 (Apr 25). doi: 10.1001/jamaoncol.2024.0578 Source
Key clinical point: Axillary lymph node dissection (ALND) can be omitted in node-positive breast cancer (BC) as only 1% of patients who achieved nodal pathological complete response (pCR) with neoadjuvant chemotherapy reported axillary recurrence (AR) in 5 years.
Major finding: The AR rate was very low at 0.65% (95% CI 0.29%-1.30%) and 1.0% (95% CI 0.49%-2.00%) at 3 years and 5 years, respectively, in patients who omitted ALND and underwent targeted axillary dissection (TAD) or sentinel lymph node biopsy (SLNB). AR rates were comparable in both surgical cohorts at 3 years (P = .55).
Study details: This retrospective cohort study included 1144 patients with node-positive BC who achieved nodal pCR with neoadjuvant chemotherapy, of whom 58.2% and 41.8% underwent SLNB and TAD, respectively.
Disclosures: This study was supported in part by a US National Institutes of Health and US National Cancer Institute Cancer Center support grant. Several authors declared receiving personal fees, grants, or consulting fees from or having other ties with various sources.
Source: Montagna G, Mrdutt MM, Sun SX, et al. Omission of axillary dissection following nodal downstaging with neoadjuvant chemotherapy. JAMA Oncol. 2024 (Apr 25). doi: 10.1001/jamaoncol.2024.0578 Source
Key clinical point: Axillary lymph node dissection (ALND) can be omitted in node-positive breast cancer (BC) as only 1% of patients who achieved nodal pathological complete response (pCR) with neoadjuvant chemotherapy reported axillary recurrence (AR) in 5 years.
Major finding: The AR rate was very low at 0.65% (95% CI 0.29%-1.30%) and 1.0% (95% CI 0.49%-2.00%) at 3 years and 5 years, respectively, in patients who omitted ALND and underwent targeted axillary dissection (TAD) or sentinel lymph node biopsy (SLNB). AR rates were comparable in both surgical cohorts at 3 years (P = .55).
Study details: This retrospective cohort study included 1144 patients with node-positive BC who achieved nodal pCR with neoadjuvant chemotherapy, of whom 58.2% and 41.8% underwent SLNB and TAD, respectively.
Disclosures: This study was supported in part by a US National Institutes of Health and US National Cancer Institute Cancer Center support grant. Several authors declared receiving personal fees, grants, or consulting fees from or having other ties with various sources.
Source: Montagna G, Mrdutt MM, Sun SX, et al. Omission of axillary dissection following nodal downstaging with neoadjuvant chemotherapy. JAMA Oncol. 2024 (Apr 25). doi: 10.1001/jamaoncol.2024.0578 Source
Postpartum BC Diagnosis Raises Mortality Risk in Women With BRCA Mutations
Key clinical point: Breast cancer (BC) diagnosed between five to <10 years postpartum (PP) was associated with a high mortality risk in women with young-onset BC (age ≤ 45 years) who had germline BRCA1/2 pathogenic variants (PV), particularly the BRCA1 mutation.
Major finding: Women with PPBC diagnosed within 5-10 years had an almost 1.5-fold higher mortality risk than nulliparous women (adjusted hazard ratio [aHR] 1.56; P = .03), with the risk being even more prominent in BRCA1 carriers (aHR 2.03; P = .02) and those with estrogen receptor-negative BC (aHR 3.12; P = .02).
Study details: This prospective cohort study included 903 women with germline BRCA1/2 PV diagnosed with stages I-III BC at age ≤ 45 years, of whom 224 were nulliparous at the time of BC diagnosis.
Disclosures: This study was supported by Oregon Health & Science University's Knight Cancer Institute, US National Institutes of Health, US National Cancer Institute, and other sources. Two authors declared receiving personal fees from various sources.
Source: Zhang Z, Ye S, Bernhardt SM, et al. Postpartum breast cancer and survival in women with germline BRCA pathogenic variants. JAMA Netw Open. 2024;7(4):e247421. doi: 10.1001/jamanetworkopen.2024.7421 Source
Key clinical point: Breast cancer (BC) diagnosed between five to <10 years postpartum (PP) was associated with a high mortality risk in women with young-onset BC (age ≤ 45 years) who had germline BRCA1/2 pathogenic variants (PV), particularly the BRCA1 mutation.
Major finding: Women with PPBC diagnosed within 5-10 years had an almost 1.5-fold higher mortality risk than nulliparous women (adjusted hazard ratio [aHR] 1.56; P = .03), with the risk being even more prominent in BRCA1 carriers (aHR 2.03; P = .02) and those with estrogen receptor-negative BC (aHR 3.12; P = .02).
Study details: This prospective cohort study included 903 women with germline BRCA1/2 PV diagnosed with stages I-III BC at age ≤ 45 years, of whom 224 were nulliparous at the time of BC diagnosis.
Disclosures: This study was supported by Oregon Health & Science University's Knight Cancer Institute, US National Institutes of Health, US National Cancer Institute, and other sources. Two authors declared receiving personal fees from various sources.
Source: Zhang Z, Ye S, Bernhardt SM, et al. Postpartum breast cancer and survival in women with germline BRCA pathogenic variants. JAMA Netw Open. 2024;7(4):e247421. doi: 10.1001/jamanetworkopen.2024.7421 Source
Key clinical point: Breast cancer (BC) diagnosed between five to <10 years postpartum (PP) was associated with a high mortality risk in women with young-onset BC (age ≤ 45 years) who had germline BRCA1/2 pathogenic variants (PV), particularly the BRCA1 mutation.
Major finding: Women with PPBC diagnosed within 5-10 years had an almost 1.5-fold higher mortality risk than nulliparous women (adjusted hazard ratio [aHR] 1.56; P = .03), with the risk being even more prominent in BRCA1 carriers (aHR 2.03; P = .02) and those with estrogen receptor-negative BC (aHR 3.12; P = .02).
Study details: This prospective cohort study included 903 women with germline BRCA1/2 PV diagnosed with stages I-III BC at age ≤ 45 years, of whom 224 were nulliparous at the time of BC diagnosis.
Disclosures: This study was supported by Oregon Health & Science University's Knight Cancer Institute, US National Institutes of Health, US National Cancer Institute, and other sources. Two authors declared receiving personal fees from various sources.
Source: Zhang Z, Ye S, Bernhardt SM, et al. Postpartum breast cancer and survival in women with germline BRCA pathogenic variants. JAMA Netw Open. 2024;7(4):e247421. doi: 10.1001/jamanetworkopen.2024.7421 Source
Second Primary BC Risk Low in Young BC Survivors Without Germline Mutations
Key clinical point: Young breast cancer (BC) survivors with a germline pathogenic variant had a higher risk for second primary breast cancer (SPBC) in the first 10 years after diagnosis than those without any mutation.
Major finding: Over a median follow-up of 10 years, 2.5% of BC survivors developed an SPBC. The SPBC risk was around five times higher in carriers vs noncarriers of germline pathogenic variants (subdistribution hazard ratio [sHR] 5.27; P = .01) and in women with primary in situ vs invasive BC (10.4% vs 2.1%; sHR 5.61; P = .01).
Study details: This prospective cohort study included 685 women diagnosed with stages 0-III BC at age ≤ 40 years who underwent unilateral mastectomy or lumpectomy as the primary surgery.
Disclosures: This study was funded by Susan G. Komen and the Breast Cancer Research Foundation. Four authors declared receiving grants or author royalties from various sources.
Source: Brantley KD, Rosenberg SM, Collins LC, et al. Second primary breast cancer in young breast cancer survivors. JAMA Oncol. 2024 (Apr 11). doi: 10.1001/jamaoncol.2024.0286 Source
Key clinical point: Young breast cancer (BC) survivors with a germline pathogenic variant had a higher risk for second primary breast cancer (SPBC) in the first 10 years after diagnosis than those without any mutation.
Major finding: Over a median follow-up of 10 years, 2.5% of BC survivors developed an SPBC. The SPBC risk was around five times higher in carriers vs noncarriers of germline pathogenic variants (subdistribution hazard ratio [sHR] 5.27; P = .01) and in women with primary in situ vs invasive BC (10.4% vs 2.1%; sHR 5.61; P = .01).
Study details: This prospective cohort study included 685 women diagnosed with stages 0-III BC at age ≤ 40 years who underwent unilateral mastectomy or lumpectomy as the primary surgery.
Disclosures: This study was funded by Susan G. Komen and the Breast Cancer Research Foundation. Four authors declared receiving grants or author royalties from various sources.
Source: Brantley KD, Rosenberg SM, Collins LC, et al. Second primary breast cancer in young breast cancer survivors. JAMA Oncol. 2024 (Apr 11). doi: 10.1001/jamaoncol.2024.0286 Source
Key clinical point: Young breast cancer (BC) survivors with a germline pathogenic variant had a higher risk for second primary breast cancer (SPBC) in the first 10 years after diagnosis than those without any mutation.
Major finding: Over a median follow-up of 10 years, 2.5% of BC survivors developed an SPBC. The SPBC risk was around five times higher in carriers vs noncarriers of germline pathogenic variants (subdistribution hazard ratio [sHR] 5.27; P = .01) and in women with primary in situ vs invasive BC (10.4% vs 2.1%; sHR 5.61; P = .01).
Study details: This prospective cohort study included 685 women diagnosed with stages 0-III BC at age ≤ 40 years who underwent unilateral mastectomy or lumpectomy as the primary surgery.
Disclosures: This study was funded by Susan G. Komen and the Breast Cancer Research Foundation. Four authors declared receiving grants or author royalties from various sources.
Source: Brantley KD, Rosenberg SM, Collins LC, et al. Second primary breast cancer in young breast cancer survivors. JAMA Oncol. 2024 (Apr 11). doi: 10.1001/jamaoncol.2024.0286 Source