Increased Overall Mortality Even after Risk Reducing Surgery for BRCA-Positive Women in Western Sweden.

Anna Öfverholm,Per Karsson,Antonia Wigermo,Zakaria Einbeigi,Erik Holmberg

doi:10.3390/genes10121046

Anna Öfverholm, Per Karsson + Show 3 more

Open Access

https://doi.org/10.3390/genes10121046

Copy DOI

Abstract

Women with BRCA variants have a high lifetime risk of developing breast and ovarian cancer. The aim of this study was to investigate the standard incidence ratios (SIR) for breast and ovarian cancer and standard mortality ratios (SMR) in a population-based cohort of women in Western Sweden, under surveillance and after risk reducing surgery. Women who tested positive for a BRCA variant between 1995–2016 (n = 489) were prospectively registered and followed up for cancer incidence, risk reducing surgery and mortality. The Swedish Cancer Register was used to compare breast and ovarian cancer incidence and mortality with and without risk reducing surgery for women with BRCA variants in comparison to women in the general population. SIR for breast cancer under surveillance until risk-reducing mastectomy (RRM) was 14.0 (95% CI 9.42–20.7) and decreased to 1.93 (95% CI 0.48–7.7) after RRM. The SIR for ovarian cancer was 124.6 (95% CI 59.4–261.3) under surveillance until risk reducing salpingo-oophorectomy (RRSO) and decreased to 13.5 (95% CI 4.34–41.8) after RRSO. The SMR under surveillance before any risk reducing surgery was 5.56 (95% 2.09–14.8) and after both RRM and RRSO 4.32 (95% CI 1.62–11.5). Women with cancer diagnoses from the pathology report after risk reducing surgery were excluded from the analyses. Risk reducing surgery reduced the incidence of breast and ovarian cancer in women with BRCA variants. However, overall mortality was significantly increased in comparison to the women in the general population and remained elevated even after risk reducing surgery. These findings warrant further research regarding additional measures for these women.

Highlights

The BRCA1 and BRCA2 genes were discovered in the early 1990s [1,2]
In Sweden, oncogenetic clinics were established at university hospitals in the six national healthcare regions (North, Uppsala-Örebro, Stockholm, West, Southeast, and South) as BRCA screening was implemented for women with hereditary breast and ovarian cancer
We evaluated cancer incidence and mortality among cancer-free women who underwent risk-reducing mastectomy (RRM) and risk reducing salpingo-oophorectomy (RRSO) in comparison with baseline risks without risk reducing surgery and in comparison with the general female population

Summary

Introduction

In Sweden, oncogenetic clinics were established at university hospitals in the six national healthcare regions (North, Uppsala-Örebro, Stockholm, West, Southeast, and South) as BRCA screening was implemented for women with hereditary breast and ovarian cancer. Each oncogenetic clinic was comprised of a team of oncologists, clinical geneticists, clinical laboratory geneticists and oncology nurses that could provide genetic counseling and screening for patients and families with hereditary breast and ovarian cancer. The oncogenetic clinic at Sahlgrenska University Hospital in Gothenburg, Sweden was established in 1995 and currently serves Western Sweden with a population of 1.9 million inhabitants. A novel recurrent founder variant in BRCA1 with origins in Western Sweden was discovered during the first years of BRCA screening at the Clinical Genetics laboratory [3,4].

Objectives

Methods

Results

Discussion

Conclusion