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Cancers (Basel). 2019 May 28;11(6). pii: E738. doi: 10.3390/cancers11060738.

Estrogen Receptor Status Oppositely Modifies Breast Cancer Prognosis in BRCA1/BRCA2 Mutation Carriers Versus Non-Carriers.

Author information

1
Department of Oncology, First Faculty of Medicine, Charles University and General University Hospital, U Nemocnice 499/2, 128 00 Prague 2, Czech Republic. michal.vocka@vfn.cz.
2
Department of Oncology, First Faculty of Medicine, Charles University and General University Hospital, U Nemocnice 499/2, 128 00 Prague 2, Czech Republic. martina.zimovjanova@vfn.cz.
3
Department of Oncology, First Faculty of Medicine, Charles University and General University Hospital, U Nemocnice 499/2, 128 00 Prague 2, Czech Republic. zuzana.bielcikova@vfn.cz.
4
Department of Oncology, First Faculty of Medicine, Charles University and General University Hospital, U Nemocnice 499/2, 128 00 Prague 2, Czech Republic. petra.tesarova@vfn.cz.
5
Department of Oncology, First Faculty of Medicine, Charles University and General University Hospital, U Nemocnice 499/2, 128 00 Prague 2, Czech Republic. lubos.petruzelka@vfn.cz.
6
Department of Oncology, First Faculty of Medicine, Charles University and General University Hospital, U Nemocnice 499/2, 128 00 Prague 2, Czech Republic. martin.mateju@vfn.cz.
7
Department of Oncology, First Faculty of Medicine, Charles University and General University Hospital, U Nemocnice 499/2, 128 00 Prague 2, Czech Republic. ludmila.krizova@vfn.cz.
8
Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University and General University Hospital, Albertov 4, 128 00 Prague 2, Czech Republic. jaroslav.kotlas@vfn.cz.
9
Institute of Biochemistry and Experimental Oncology, First Faculty of Medicine, Charles University, U Nemocnice 5, 128 00 Prague 2, Czech Republic. jana.soukupova@lf1.cuni.cz.
10
Institute of Biochemistry and Experimental Oncology, First Faculty of Medicine, Charles University, U Nemocnice 5, 128 00 Prague 2, Czech Republic. marketa.janatova@lf1.cuni.cz.
11
Institute of Biochemistry and Experimental Oncology, First Faculty of Medicine, Charles University, U Nemocnice 5, 128 00 Prague 2, Czech Republic. petra.zemankova@lf1.cuni.cz.
12
Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University and General University Hospital, Albertov 4, 128 00 Prague 2, Czech Republic. pekleje@lf1.cuni.cz.
13
Institute of Biochemistry and Experimental Oncology, First Faculty of Medicine, Charles University, U Nemocnice 5, 128 00 Prague 2, Czech Republic. pekleje@lf1.cuni.cz.
14
Department of Surgery, Sunderby Hospital, Sjukhusvägen 10, 954 42 Sunderbyn, Sweden. onkologie@seznam.cz.
15
Department of Oncology, First Faculty of Medicine, Charles University and General University Hospital, U Nemocnice 499/2, 128 00 Prague 2, Czech Republic. bohuslav.konopasek@vfn.cz.
16
Department of Oncology, Chomutov Hospital, Kochova 1185, 430 01 Chomutov, Czech Republic. martina.chodacka@kzcr.eu.
17
Department of Radiotherapy and Oncology, Third Faculty of Medicine, Charles University and Faculty Hospital Kralovske Vinohrady, Srobarova 1150/50, 100 34 Prague 10, Czech Republic. brychta@fnkv.cz.
18
Department of Oncology, Vzdusna 1360/6, 460 01 Liberec, Czech Republic. sochor.marek73@gmail.com.
19
Department of Oncology, Masaryk Hospital, Socialni pece 3316/12, 401 13 Usti nad Labem, Czech Republic. denisa.smejkalovamusilova@kzcr.eu.
20
Department of Oncology, Second Faculty of Medicine, Charles University and Motol University Hospital, V Uvalu 84, 150 06 Prague 5, Czech Republic. v.cmejlova@seznam.cz.
21
Department of Oncology, Medicon, Roskotova 1717/2, 140 00 Prague 4, Czech Republic. r.kozevnikovova@email.cz.
22
Department of Oncology, First Faculty of Medicine, Charles University and Thomayer Hospital, Videnska 800, 140 59 Prague 4, Czech Republic. lenka.mockova@gmail.com.
23
Institute of Radiation Oncology, First Faculty of Medicine, Charles University and Hospital Na Bulovce, Budinova 2, 180 00 Prague 8, Czech Republic. argi@centrum.cz.
24
Institute of Biochemistry and Experimental Oncology, First Faculty of Medicine, Charles University, U Nemocnice 5, 128 00 Prague 2, Czech Republic. lenka.stolarova@lf1.cuni.cz.
25
Institute of Biochemistry and Experimental Oncology, First Faculty of Medicine, Charles University, U Nemocnice 5, 128 00 Prague 2, Czech Republic. klara.lhotova@lf1.cuni.cz.
26
Institute of Biochemistry and Experimental Oncology, First Faculty of Medicine, Charles University, U Nemocnice 5, 128 00 Prague 2, Czech Republic. marianna.borecka@lf1.cuni.cz.
27
Institute of Biochemistry and Experimental Oncology, First Faculty of Medicine, Charles University, U Nemocnice 5, 128 00 Prague 2, Czech Republic. zdekleje@lf1.cuni.cz.

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.

KEYWORDS:

BRCA1; BRCA2; breast cancer; estrogen receptor; germline mutations; survival

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