Assessing the Risk of Future Contralateral Breast Cancer in Carriers of Certain Germline Pathogenic Variants

By: Amy MacDonald, MS
Posted: Monday, March 27, 2023

What is a breast cancer survivor’s risk of developing future contralateral breast cancer? Previous studies have focused primarily on assessing this scenario in high-risk younger patients with a known family history (most commonly of BRCA1 or BRCA2 mutations). However, the ability to estimate this risk in all patients who harbor germline mutations in the expanding list of breast cancer–linked DNA repair genes (ATM, BRCA1, BRCA2, CHEK2, and PALB2) is also needed.

Fergus J. Couch, PhD, of the Mayo Clinic, Rochester and colleagues looked at the relationship between germline pathogenic variant data from the Cancer Risk Estimates Related to Susceptibility (CARRIERS) consortium and contralateral breast cancer risk. Published in the Journal of Clinical Oncology, their data demonstrated that women with breast cancer who carry germline mutations in BRCA1, BRCA2, CHEK2, or PALB2 have a substantially increased risk of future contralateral breast cancer.

Specifically, the researchers determined that patients harboring germline mutations in BRCA1, BRCA2, and CHEK2 had a significantly higher risk of contralateral cancer (hazard ratio [HR] > 1.9), yet the PALB2 carriers alone, who also had estrogen receptor [ER]-negative breast cancer, faced an elevated risk (HR = 2.9). Among premenopausal women with breast cancer, the 10-year cumulative incidence of contralateral breast cancer was estimated to be 33% for BRCA1, 27% for BRCA2, and 13% for CHEK2 carriers; and 35% for PALB2 carriers with ER-negative breast cancer. Of note, the 10-year cumulative incidence of contralateral breast cancer for postmenopausal carriers was lower: 12% for BRCA1, 9% for BRCA2, and 4% for CHEK2.

Finally, because more than 20% of premenopausal women with pathologic variants in the BRCA1, BRCA2, CHEK2, and PALB2 genes were found to have developed contralateral breast cancer within 15 years, aggressive clinical surveillance with MRI and mammography is warranted in this patient population.

Disclosure: For full disclosures of the study authors, visit ascopubs.org.

Journal of Clinical Oncology