In an English study reported in the Journal of Clinical Oncology, Allen et al found that patients with breast cancer harboring BRCA1/BRCA2 pathogenic variants were at high risk of second primary cancers.
Study Details and Results
The study involved follow-up of 25,811 females and 480 males diagnosed with breast cancer. Investigators tested for germline BRCA1/BRCA2 pathogenic variants in NHS Clinical Genetics centers in England between 1995 and 2019.
A total of 1,840 BRCA1 and 1,750 BRCA2 female pathogenic variant carriers were identified. Compared with the general population, BRCA1 carriers with breast cancer had an increased risk for contralateral breast cancer (standardized incidence ratio [SIR] = 15.6, 95% confidence interval [CI] = 11.8–20.2), ovarian cancer (SIR = 44.0, 95% CI = 31.4–59.9), combined nonbreast/ovarian cancers (SIR = 2.18, 95% CI = 1.59–2.92), colorectal cancer (SIR= 4.80, 95% CI = 2.62–8.05), and endometrial cancer (SIR = 2.92, 95% CI = 1.07–6.35).
Female BRCA2 carriers with breast cancer had an increased risk for contralateral breast cancer (SIR = 7.70, 95% CI = 5.45–10.6), ovarian cancer (SIR = 16.8, 95% CI = 10.3–26.0), pancreatic cancer (SIR = 5.42, 95% CI = 2.09–12.5), and combined nonbreast/ovarian cancers (SIR= 1.68, 95% CI = 1.24–2.23).
Compared with females without BRCA1/BRCA2 pathogenic variants, BRCA1 carriers had increased second primary cancer risks for contralateral breast cancer (hazard ratio [HR] = 3.60, 95% CI = 2.65–4.90), ovarian cancer (HR= 33.0, 95% CI = 19.1–57.1), combined nonbreast/ovarian cancers (HR= 1.45, 95% CI = 1.05–2.01), and colorectal cancer (HR= 2.93, 95% CI = 1.53–5.62). BRCA2 carriers had increased risk for contralateral breast cancer (HR = 2.40, 95% CI = 1.70–3.40), ovarian cancer (HR= 12.0, 95% CI = 6.70–21.5), and pancreatic cancer (HR = 3.56, 95% CI = 1.34–9.48).
Among women with breast cancer, 10-year cumulative contralateral breast cancer, ovarian cancer, and combined nonbreast/ovarian cancer risks were 16%, 6.3%, and 7.8% among BRCA1 carriers; 12%, 3.0%, and 6.2% among BRCA2 carriers; and 3.6%, 0.4%, and 4.9% among noncarriers.
Male BRCA2 carriers with breast cancer had an increased risk of contralateral breast cancer (HR = 13.1, 95% CI = 1.19–1.46) and prostate cancer (HR= 5.61, 95% CI = 1.96–16.0) vs noncarriers.
The investigators concluded: “Survivors of breast cancer carrying BRCA1 and BRCA2 pathogenic variants are at high second primary cancer risk. They may benefit from enhanced surveillance and risk-reduction measures.”
Isaac Allen, BSc, of the Department of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge, is the corresponding author of the Journal of Clinical Oncology article.
Disclosure: The study was supported by the CRUK Catalyst Award CanGene-CanVar, Cancer Research UK, and others. For full disclosures of the study authors, visit ascopubs.org.
