Second Primary Cancers in Breast Cancer Survivors With BRCA1/2 Pathogenic Variants

By: Julia Cipriano, MS
Posted: Wednesday, December 4, 2024

Based on the results of a retrospective analysis, which were published in the Journal of Clinical Oncology, breast cancer survivors with BRCA1/2 pathogenic variants have a high risk of developing second primary cancers. According to Antonis C. Antoniou, PhD, of the University of Cambridge, United Kingdom, and colleagues, this population may benefit from enhanced surveillance and risk-reduction measures.

Using electronic health records and genetic testing data, the investigators established a cohort of 25,811 female survivors of nonmetastatic invasive breast cancer. Of this population, 1,840 and 1,750 were carriers of BRCA1 and BRCA2 pathogenic variants, respectively.

Compared with the general population, BRCA1 carriers were found to have an elevated risk of developing contralateral breast (standardized incidence ratio [SIR] = 15.6), ovarian (SIR = 44.0), nonbreast or ovarian (combined SIR = 2.2), colorectal (SIR = 4.8), and endometrial (SIR = 2.9) cancer. Carriers of BRCA2 pathogenic variants appeared to have an increased likelihood of developing contralateral breast (SIR = 7.7), ovarian (SIR = 16.8), pancreatic (SIR = 5.4), and nonbreast or ovarian (combined SIR = 1.7) cancer.

The investigators reported that patients with BRCA1 vs those without BRCA1/2 pathogenic variants had an increased risk of developing contralateral breast (hazard ratio [HR] = 3.6), ovarian (HR = 33.0), nonbreast or ovarian (combined HR = 1.5), and colorectal (HR = 2.9) cancer. Increased risks of developing contralateral breast (HR = 2.4), ovarian (HR = 12.0), and pancreatic (HR = 3.6) cancer were identified in those carrying BRCA2 pathogenic variants. The 10-year cumulative risks of developing contralateral breast, ovarian, and nonbreast or ovarian cancer were 16%, 6.3%, and 7.8% in BRCA1 carriers, 12%, 3.0%, and 6.2% in BRCA2 carriers, and 3.6%, 0.4%, and 4.9% in noncarriers, respectively.

“Risks were particularly elevated in females [who were] younger at [their] first breast cancer diagnosis,” the investigators remarked.

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

Journal of Clinical Oncology