Estrogen Receptor Status Oppositely Modifies Breast Cancer Prognosis in BRCA1/BRCA2Mutation Carriers Versus Non-Carriers.

Vocka M1, Zimovjanova M2, Bielcikova Z3, Tesarova P4, Petruzelka L5, Mateju M6, Krizova L7, Kotlas J8, Soukupova J9, Janatova M10, Zemankova P11, Kleiblova P12,13, Novotny J14, Konopasek B15, Chodacka M16, Brychta M17, Sochor M18, Smejkalova-Musilova D19, Cmejlova V20, Kozevnikovova R21, Miskarova L22, Argalacsova S23, Stolarova L24, Lhotova K25, Borecka M26, Kleibl Z27.

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Abstract

Breast cancer (BC) prognosis in BRCA1 and BRCA2 mutation carriers has been reported contradictorily, and the significance of variables influencing prognosis in sporadic BC is not established in BC patients with hereditary BRCA1/BRCA2 mutations. In this retrospective cohort study, we analyzed the effect of clinicopathological characteristics on BC prognosis (disease-free survival [DFS] and disease-specific survival [DSS]) in hereditary BRCA1/BRCA2 mutation carriers. We enrolled 234 BRCA1/BRCA2 mutation carriers and 899 non-carriers, of whom 191 carriers and 680 non-carriers, with complete data, were available for survival analyses. We found that patients with ER-positive tumors developed disease recurrence 2.3-times more likely when they carried a BRCA1/BRCA2 mutation (23/60; 38.3% ER-positive carriers vs. 74/445; 16.6% ER-positive non-carriers; p < 0.001). ER-positive mutation carriers also had a 3.4-times higher risk of death due to BC compared with ER-positive non-carriers (13/60; 21.7% vs. 28/445; 6.3%; p < 0.001). Moreover, prognosis in ER-negative BRCA1/BRCA2 mutation carriers was comparable with that in ER-positive non-carriers. Our study demonstrates that ER-positivity worsens BC prognosis in BRCA1/BRCA2 mutation carriers, while prognosis for carriers with ER-negative tumors (including early-onset) is significantly better and comparable with that in ER-positive, older BC non-carriers. These observations indicate that BRCA1/BRCA2 mutation carriers with ER-positive BC represent high-risk patients.