Timing of risk reducing mastectomy in breast cancer patients carrying a BRCA1/2 mutation: retrospective data from the Dutch HEBON study.

M R Wevers,M Collée,M A Rookus,C J Van Asperen,E G Engelhardt,L B Koppert,M J Hooning,M Kriege,S Verhoef,M G E M Ausems,A J Witkamp,N K Aaronson,C Seynaeve,E J T Rutgers,R A E M Tollenaar,M K Schmidt

doi:10.1007/s10689-015-9788-x

Abstract

It is expected that rapid genetic counseling and testing (RGCT) will lead to increasing numbers of breast cancer (BC) patients knowing their BRCA1/2 carrier status before primary surgery. Considering the potential impact of knowing one’s status on uptake and timing of risk-reducing contralateral mastectomy (RRCM), we aimed to evaluate trends over time in RRCM, and differences between carriers identified either before (predictively) or after (diagnostically) diagnosis. We collected data from female BRCA1/2 mutation carriers diagnosed with BC between 1995 and 2009 from four Dutch university hospitals. We compared the timing of genetic testing and RRCM in relation to diagnosis in 1995–2000 versus 2001–2009 for all patients, and predictively and diagnostically tested patients separately. Of 287 patients, 219 (76 %) had a diagnostic BRCA1/2 test. In this cohort, the median time from diagnosis to DNA testing decreased from 28 months for those diagnosed between 1995 and 2000 to 14 months for those diagnosed between 2001 and 2009 (p < 0.001). Similarly, over time women in this cohort underwent RRCM sooner after diagnosis (median of 77 vs. 27 months, p = 0.05). Predictively tested women who subsequently developed BC underwent an immediate RRCM significantly more often than women who had a diagnostic test (21/61, 34 %, vs. 13/170, 7.6 %, p < 0.001). Knowledge of carrying a BRCA1/2 mutation when diagnosed with BC influenced decisions concerning primary surgery. Additionally, in more recent years, women who had not undergone predictive testing were more likely to undergo diagnostic DNA testing and RRCM sooner after diagnosis. This suggests the need for RGCT to guide treatment decisions.Electronic supplementary materialThe online version of this article (doi:10.1007/s10689-015-9788-x) contains supplementary material, which is available to authorized users.

Highlights

Female BRCA1 or BRCA2 gene mutation carriers have an increased risk of developing breast cancer of 27–88 %, and a maximum lifetime risk of developing ovarian cancer of 6–59 % [1, 2]
The following data were retrieved from the HEBON-database: date of birth; tumor characteristics [ductal carcinoma in situ (DCIS) or invasive breast cancer, TNM stage, unilateral or bilateral breast cancer, date of diagnosis]; history of other cancers; mutated gene (BRCA1 or BRCA2); date of DNA test result; type of Clinical and sociodemographic characteristics of the sample
Our data clearly indicate that women known to be carrier before breast cancer diagnosis opted significantly more often for an immediate reducing contralateral mastectomy (RRCM) than those who had a DNA test after cancer diagnosis

Summary

Introduction

Female BRCA1 or BRCA2 gene mutation carriers have an increased risk of developing breast cancer of 27–88 %, and a maximum lifetime risk of developing ovarian cancer of 6–59 % [1, 2]. Once diagnosed with unilateral breast cancer, BRCA1/2 mutation carriers have a 16–55 % risk of developing contralateral breast cancer within 25 years, depending on, among other factors, age at first diagnosis and the mutated gene [3, 4]. Breast cancer patients at risk of having hereditary cancer are typically referred for genetic counseling and diagnostic DNA testing after their primary treatment [14–17]. In such cases, affected carriers may consider undergoing a delayed RRCM [18]. Unaffected women who become aware of their carrier status via a predictive DNA test (i.e. while still asymptomatic) and subsequently develop breast cancer, may consider an immediate RRCM (i.e. at the time of the therapeutic surgery)

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