Abstract P2-07-04: Risk of primary and contralateral breast cancer in BRCA1/2 mutation carriers previously affected with ovarian cancer
Authors: Heemskerk-Gerritsen BAM , Hooning MJ , van Doorn HC , Collée MJ , Koppert LB , Jager A , van den Ouweland AMW , Netherlands H , Seynaeve C , Kriege M 
Published: March 2017

Introduction: BRCA1/2 mutation carriers are at increased risk of developing breast cancer (BC) and ovarian cancer (OC). However, for BRCA1/2 mutation carriers previously affected with OC, primary BC (PBC) and contralateral BC (CBC) risks might be lowered due to OC treatment, but data hereon are limited. Accurate BC risk estimates are essential for counseling and optimal decision making on BC surveillance and risk-reducing mastectomy (RRM) after diagnosis of BRCA1/2-associated OC.

Methods: From the national HEBON cohort study, we selected female BRCA1/2 mutation carriers born from 1940 and at risk of PBC (n=2019; 1194 BRCA1, 825 BRCA2) or at risk of CBC (n=1276; 839 BRCA1, 437 BRCA2). Eligibility criteria for the PBC risk analyses included no history of PBC and both breasts in situ at DNA testing. For the CBC risk analyses, CBC before DNA testing was not allowed and the contralateral breast had to be unaffected at DNA testing. To estimate the association between OC and BC risk, we used the Fine and Gray regression model, with OC as a time-dependent variable and death as competing risk event. The observation started at the age of DNA testing, age 35, or – for the CBC risk analyses – age at PBC diagnosis, whichever came last. Censoring events were RRM, study closing date (i.e. 2014-12-31), and – for the CBC risk analyses – ipsilateral BC recurrence. All analyses were performed separately for BRCA1 and BRCA2 mutation carriers.

Results: For the PBC analyses, we selected 236 BRCA1/2 mutation carriers with OC and 1783 BRCA1/2 mutation carriers without OC (median age at start study 53 and 41 years, respectively). During a mean follow-up (FU) of 5.2 years, 15 (6%) OC patients developed PBC after OC, while PBC was diagnosed in 262 (15%) women without OC. OC diagnosis was associated with a lower PBC risk in BRCA1 mutation carriers (HR, 0.27; 95% CI, 0.14–0.53) but not in BRCA2 mutation carriers (HR, 0.88; 95% CI, 0.34–2.27). The cumulative PBC incidence at age 70 in BRCA1 mutation carriers was 25% for OC patients and 66% for women without OC, and in BRCA2 mutation carriers 49% for OC patients and 53% for women without OC.

For the CBC analyses, we selected 99 BRCA1/2 mutation carriers affected with PBC and OC, and 1177 BRCA1/2-associated PBC patients without OC (median age at start study 54 and 46 years, respectively). During a mean FU of 3.5 years, 8 (8%) PBC/OC patients developed CBC after OC, while CBC was diagnosed in 131 (11%) PBC patients without OC. In BRCA1 mutation carriers, OC diagnosis was non-significantly associated with a lower CBC risk (HR, 0.44; 95% CI, 0.19–1.03). For BRCA2 mutation carriers the HR was 1.65 (95% CI, 0.34–8.04). The cumulative CBC incidence at age 70 in BRCA1 mutation carriers was 40% for OC patients and 68% for patients without OC; for BRCA2 mutation carriers the number of CBCs was too small to obtain meaningful estimates.

Conclusion:­ For BRCA1 mutation carriers affected with OC the risk of developing subsequent BC is lower than for BRCA1 mutation carriers without OC. Our data suggest that the current BC prevention strategies should be reconsidered for OC patients carrying a BRCA1 mutation, possibly including less intensive BC surveillance, and RRM being indicated only for a subgroup of OC patients.

Citation Format: Heemskerk-Gerritsen BAM, Hooning MJ, van Doorn HC, Collée MJ, Koppert LB, Jager A, van den Ouweland AMW, Netherlands H, Seynaeve C, Kriege M. Risk of primary and contralateral breast cancer in BRCA1/2 mutation carriers previously affected with ovarian cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-07-04.