Breast cancer survivors with BRCA mutations at greater risk for second primary malignancies
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Key takeaways:
- Patients with BRCA1/BRCA2-mutated breast cancer are at higher risk for second primary cancers.
- Men with BRCA2 mutations have elevated risk for contralateral breast cancer and prostate cancer.
Breast cancer survivors who harbor BRCA gene mutation are at elevated risk for second primary cancers, according to study results.
These individuals likely would benefit from enhanced surveillance and risk-reduction measures, researchers concluded.
“To our knowledge, [this] is the first study based on a linkage of germline testing laboratory data to population-scale electronic health records, minimizing selection biases common in recruitment-based cohort studies,” Isaac Allen, BSc, doctoral student at Cambridge University, and colleagues wrote. “It is based on very high-quality registry data. This work offers proof of principle that linkages of genetic testing laboratory data to population-scale electronic health records allow estimation of under-studied cancer risks in novel cohorts.”
The risk for second primary cancers among breast cancer survivors with BRCA1 or BRCA2 pathogenic variants had not been well established.
Allen and colleagues used a novel linkage of genetic testing data to population-scale electronic health records from the National Disease Registration Service and Hospital Episode Statistics to estimate relative and absolute risks.
The analysis included 26,291 people (98.17% women) diagnosed with breast cancer who received tests for germline BRCA1/BRCA2 pathogenic variants in National Health Service Clinical Genetics centers in England between 1995 and 2019.
Follow-up continued until second primary cancer, death, migration, contralateral breast/ovarian surgery plus 1 year, or Dec. 31, 2020.
Among the 25,811 women in the cohort, 1,840 (7.1%) tested positive for a BRCA1 variant and 1,750 (6.78%) tested positive for a BRCA2 variant.
Compared with the overall population, women with BRCA1 mutations exhibited greater risk for second primary cancers, including contralateral breast cancer (standardized incidence ratio [SIR] = 15.6; 95% CI, 11.8-20.2), ovarian cancer (SIR = 44; 95% CI, 31.4-59.9), combined nonbreast/nonovarian cancer (SIR = 2.18; 95% CI, 1.59-2.92), colorectal cancer (SIR = 4.8; 95% CI, 2.62-8.05) and endometrial cancer (SIR = 2.92; 95% CI, 1.07-6.35).
Women with a BRCA2 mutations had elevated risks for certain secondary primary cancers, specifically contralateral breast cancer (SIR = 7.7; 95% CI, 5.45-10.6), ovarian cancer (SIR = 16.8; 95% CI, 10.3-26), pancreatic cancer (SIR = 5.42; 95% CI, 2.09-12.5) and combined nonbreast/nonovarian cancers (SIR = 1.68; 95% CI, 1.24-2.23).
Compared with women who did not test positive for BRCA1 or BRCA2 mutations, those with BRCA1 mutations had elevated second primary cancer risk for contralateral breast cancer (HR = 3.6; 95% CI, 2.65-4.9), ovarian cancer (HR = 33; 95% CI, 19.1-57.1), combined nonbreast/nonovarian cancers (HR = 1.45; 95% CI, 1.05-2.01) and colorectal cancers (HR = 2.93; 95% CI, 1.53-5.62).
Those with BRCA2 mutations had elevated risk for contralateral breast cancer (HR = 2.4; 95% CI, 1.7-3.4), ovarian cancer (HR = 12; 95% CI, 6.7-21.5) and pancreatic cancer (HR = 3.56; 95% CI, 1.34-9.48).
Among patients with BRCA1 mutations, researchers observed 10-year cumulative incidence rates of 16% for contralateral breast cancer, 6.3% for ovarian cancer and 7.8% for combined nonbreast/nonovarian cancers.
Amont those with BRCA2 mutations, results showed 10-year cumulative incidence rates of 12% for contralateral breast cancer, 3% for ovarian cancer and 6.2% for combined nonbreast/nonovarian cancers.
Among BRCA mutation noncarriers, results showed 10-year cumulative incidence rate of 3.6% for contralateral breast cancer, 0.4% for ovarian cancer and 4.9% for combined nonbreast/nonovarian cancers.
Men with BRCA2 mutations had higher risks than noncarriers for secondary contralateral breast (HR = 13.1; 95% CI, 1.19-146) and prostate cancer (HR = 5.61; 95% CI, 1.96-16) second primary cancers than noncarriers.
Researchers acknowledged study limitations, including the fact that SIR, HR and complete response estimates among breast cancer survivors who had BRCA mutations may be inflated by surveillance bias. They also noted median follow-up of less than 4 years and a median patient age of 46 years at first breast cancer diagnosis means later- or older-onset secondary cancers could not be taken into account.
“This study demonstrates the value of population-scale electronic health record linkages, and that survivors or [patients with] breast cancer carrying BRCA1/BRCA2 pathogenic variants are at elevated cancer risks,” researchers wrote.
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