Patients with germline pathogenic variants (PVs) in BRCA1, BRCA2, and CHEK2 have an increased risk of contralateral breast cancer, according to research presented at the San Antonio Breast Cancer Symposium 2022.
Researchers also found that patients with estrogen receptor (ER)-negative breast cancer who have PVs in PALB2 have an increased risk of contralateral breast cancer, but patients with PVs in ATM do not.
The findings for ATM and PALB2 raise questions about the role of effective adjuvant endocrine therapy (ET) in this subset of patients, said study presenter Siddhartha Yadav, MD, of the Mayo Clinic in Rochester, Minnesota.
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Dr Yadav and colleagues conducted this research in a subset of patients from the CARRIERS study, which included 15,104 women with unilateral invasive breast cancer. The patients’ median age at diagnosis was 62 years, 73% of patients were postmenopausal, 75% had ER-positive disease, and 46% received adjuvant ET at first diagnosis.
Over a median follow-up of 11 years, there were 711 contralateral breast cancer events among noncarriers. There were 33 events among carriers of BRCA2 PVs, 31 events among carriers of BRCA1 PVs, 12 events among carriers of CHEK2 PVs, 7 events among carriers of ATM PVs, and 7 events among carriers of PALB2 PVs.
In an adjusted analysis, the risk of contralateral breast cancer was increased for carriers of BRCA1, BRCA2, and CHEK2 PVs in the overall population. Results were similar for patients with ER-positive disease.
Among patients with ER-negative disease, the risk of contralateral breast cancer was increased among patients with BRCA1, BRCA2, and PALB2 PVs. There were too few cases to evaluate the risk associated with ATM or CHEK2 PVs in the ER-negative population.
The researchers also stratified patients by menopausal status. Among noncarriers, the 10-year cumulative incidence of contralateral breast cancer was 5.8% for premenopausal patients and 3.7% for postmenopausal patients. Among BRCA1 PV carriers, the incidence was 33% and 11%, respectively. Among BRCA2 PV carriers, the incidence was 27% and 9.5%, respectively. Among ATM PV carriers, the incidence was 2.9% and 4.6%, respectively. Among CHEK2 PV carriers, the incidence was 13% and 4.3%, respectively.
Among patients older than 65 years at first diagnosis, 3 contralateral breast cancer events occurred during a median follow-up of 10 years, which limited the feasibility of evaluating risk in this group.
Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Reference
Yadav S, Boddicker NJ, Na J, et al. Population-based estimates of contralateral breast cancer risk among carriers of germline pathogenic variants in ATM, BRCA1, BRCA2, CHEK2, and PALB2. Presented at SABCS 2022. December 6-10, 2022. Abstract GS4-04.
