# Occurrence of Malignancies Other than Breast and Ovarian Cancer in Female Carriers of a BRCA1/2 Germline Pathogenic Variant

## TL;DR

Women with BRCA1/2 gene mutations have a higher risk of developing cancers other than breast and ovarian cancer before age 60.

## Contribution

This study provides evidence of increased risks for head and neck, gastrointestinal, and female genital cancers in BRCA1/2 carriers.

## Key findings

- An increased overall cancer risk was observed in BRCA1/2 carriers before age 60.
- Higher risks were found for head and neck, gastrointestinal, and female genital cancers.
- The study highlights the need for larger studies to confirm these findings and adjust clinical guidelines.

## Abstract

Women with a BRCA1/2 germline pathogenic variant (GPV) are at an increased risk of developing breast and ovarian cancer. Previous studies have suggested that they may also have an increased risk of developing other types of cancer at an early age. The aim of this study is to investigate this risk of developing other types of cancer before age 60. We linked data from our hospital-based data/biobank to data from the Dutch Nationwide Pathology Databank (PALGA). We included 1347 women with a BRCA1/2 GPV who had 82 diagnosed cancers (other than breast and ovarian cancer) in our study. We found an increased risk of cancer in general, as well as an increased risk of head and neck cancer, gastrointestinal cancer, and female genital cancer (ovarian cancer excluded). However, larger studies that can account for other risk factors for cancer are necessary to confirm these results

Introduction: Previous studies have suggested an additional increased risk for types of malignancies other than breast and ovarian cancer for female BRCA1/2 GPV carriers, but risk estimates vary widely. The aim of this study was to investigate if female BRCA1/2 GPV carriers have an increased risk of malignancies other than breast and tubal/ovarian cancer at an early age. Methods: Prospectively collected data from female BRCA1/2 GPV carriers in our hospital-based data/biobank were linked to the PALGA Dutch Pathology Database. Incidences of malignancies occurring before 60 years of age were compared to crude rates/100.000 person-years in the Netherlands, stratified by age and calendar time. Standardized incidence ratios (SIRs) were calculated with 95% confidence intervals (95%CIs). Results: In 1347 women, 82 malignancies other than breast and tubal/ovarian cancer were detected in patients under 60 years of age in 37,068 person-years. An increased risk of cancer in general (SIR:2.25, 95%CI:1.78–2.80, p < 0.001), head and neck cancer (SIR:3.17, 95%CI:1.03–7.39, p < 0.05), gastrointestinal cancer (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: If confirmed in larger, prospective studies that include the role of bias and previous cancer treatment, awareness of the possible increased risks of head and neck, gastrointestinal, and female genital cancer may be used to tailor clinical guidelines for female BRCA1/2 GPV carriers.