Occurrence of malignancies other than breast and ovarian cancer in female carriers of a BRCA1/2 germline pathogenic variant

Abstract

Abstract Background Women with BRCA1/2 germline pathogenic variants (GPV) have an increased risk of breast and tubal/ovarian cancer at an early age. Previous studies suggested an additional increased risk for other types of malignancies at early age, but risk estimates vary widely. The aim of the current study was investigate if female BRCA1/2 GPV carriers have an increased risk of malignancies other than breast and ovarian cancer at an early age. Methods Since 1994, women with a BRCA1/2 GPV are prospectively included in a data/biobank at our university hospital. Data were linked to PALGA: Dutch Pathology Registry. The primary outcome was defined as the incidence of malignancies other than breast and tubal/ovarian cancer before the age of 60 years and coded according to the International Classification of Diseases for Oncology. Incidences were compared to crude rates/100.000 person-years for the Netherlands, stratified by age and calendar time. Standardized incidence ratios (SIRs) were calculated with 95% confidence intervals (95%CIs). Results From 1347 women, 37,068 person-years were available, in which 82 malignancies other than breast and ovarian cancer under age 60 were detected. An increased risk of cancer in general (excluding breast and tubal/ovarian cancer) (SIR:2.25, 95%CI:1.78–2.80, P < 0.001), head and neck (SIR:3.17, 95%CI:1.03–7.39, p < 0.05), gastro-intestinal (SIR:1.96, 95%CI:1.14–3.13, p < 0.05) and female genital cancer (SIR:2.48, 95%CI:1.61–3.65, p < 0.001) was found. Conclusions Female carriers of BRCA1/2 GPV under 60 years of age have an increased risk to develop cancer in general (excluding breast and tubal/ovarian cancer), especially head and neck, gastro-intestinal and female genital cancer. If confirmed in larger, prospective studies that include the role of bias and previous cancer treatment, awareness of these risks could tailor prevention strategies and/or surveillance.