BRCA1/2 Carriers Face Higher Risk for Second Primary Cancer

TOPLINE:

Survivors of breast cancer who carry BRCA1 or BRCA2 pathogenic variants face increased risks for second primary cancers, including contralateral breast cancer, ovarian cancer, and colorectal cancer. The 10-year cumulative risk for contralateral breast cancer, for instance, was 16% in BRCA1 carriers and 12% in BRCA2 carriers.

METHODOLOGY:

• The risk for second primary cancer among breast cancer survivors who carry BRCA1 and BRCA2 germline variants is not well understood. Having precise estimates could inform cancer surveillance and risk-reduction options in this population.
• Researchers conducted a retrospective cohort study involving 25,811 female and 480 male survivors of invasive, nonmetastatic breast cancer and who were tested for BRCA1/BRCA2 pathogenic variants at NHS Clinical Genetics centers in England between 1995 and 2019. More than 80% of patients were White.
• Among all patients, 1840 women were BRCA1 carriers (7.1%) and 1750 were BRCA2 carriers (6.8%), while seven men were BRCA1 carriers (1.46%) and 74 were BRCA2 carriers (15.4%).
• The study outcome was second primary cancer within a year of contralateral breast or ovarian surgery.
• Median follow-up ranged from 3.5 to 3.8 years.

TAKEAWAY:

• Women with BRCA1 had increased risks for contralateral breast cancer (standardized incidence ratio [SIR], 15.6) as well as ovarian (SIR, 44.0), colorectal (SIR, 4.80), and endometrial cancers (SIR, 2.92), compared with the general population. BRCA2 carriers faced higher risks for contralateral breast (SIR, 7.70), ovarian (SIR, 16.8), and pancreatic cancers (SIR, 5.42). Some of these increases may reflect additional cancer risk factors associated with surviving breast cancer.
• Compared with noncarriers, both BRCA1 and BRCA2 carriers had increased risks for contralateral breast cancer (hazard ratio [HR], 3.60 and 2.4) and ovarian cancer (HR, 33.0 and 12.0). BRCA1 carriers also had elevated risk for colorectal cancer (HR, 2.93) and combined non-breast/ovarian cancers (HR, 1.45), while BRCA2 carriers had a higher risk for pancreatic cancer (HR, 3.56).
• Men with BRCA2 showed higher risks for contralateral breast cancer (HR, 13.1) and prostate cancer (HR, 5.61) than noncarriers.
• Among BRCA1 carriers, the 10-year cumulative risk for contralateral breast cancer, ovarian cancer, and combined non-breast/ovarian cancer was 16%, 6.3%, and 7.8%, respectively; among BRCA2 carriers, that risk was 12%, 3.0%, and 6.2%, respectively. These figures might “overestimate risks” for carriers without a family history of cancer, highlighting importance of family history in the counselling.

IN PRACTICE:

“Survivors of breast cancer carrying BRCA1/BRCA2 pathogenic variants are at elevated cancer risks,” the authors wrote, and may benefit from “ enhanced surveillance and risk-reduction measures.”

SOURCE:

The study, led by Isaac Allen, University of Cambridge in Cambridge, United Kingdom, was published online in Journal of Clinical Oncology.

LIMITATIONS:

A relatively short median follow-up period may have limited the ability to identify later-onset cancers. The low counts of non-breast, ovarian, and prostate second primary cancers may have resulted in underpowered analyses, particularly in men. The study’s findings may have been influenced by surveillance bias as cancer surveillance may be heightened after a positive BRCA1/BRCA2 pathogenic variant test.

DISCLOSURES:

The study was supported by grants from the CRUK Catalyst Award CanGene-CanVar and Cancer Research UK. The core funding was provided by the National Institute for Health and Care Research Cambridge Biomedical Research Centre. Several authors reported having various ties with various sources. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.