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Association of germline variation with the survival of women with BRCA1/2 pathogenic variants and breast cancer.

ABSTRACT: Germline genetic variation has been suggested to influence the survival of breast cancer patients independently of tumor pathology. We have studied survival associations of genetic variants in two etiologically unique groups of breast cancer patients, the carriers of germline pathogenic variants in BRCA1 or BRCA2 genes. We found that rs57025206 was significantly associated with the overall survival, predicting higher mortality of BRCA1 carrier patients with estrogen receptor-negative breast cancer, with a hazard ratio 4.37 (95% confidence interval 3.03-6.30, P?=?3.1?×?10-9). Multivariable analysis adjusted for tumor characteristics suggested that rs57025206 was an independent survival marker. In addition, our exploratory analyses suggest that the associations between genetic variants and breast cancer patient survival may depend on tumor biological subgroup and clinical patient characteristics.

SUBMITTER: Muranen TA

PROVIDER: S-EPMC7483417 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Association of germline variation with the survival of women with BRCA1/2 pathogenic variants and breast cancer.

Muranen Taru A TA Khan Sofia S Fagerholm Rainer R Aittomäki Kristiina K Cunningham Julie M JM Dennis Joe J Leslie Goska G McGuffog Lesley L Parsons Michael T MT Simard Jacques J Slager Susan S Soucy Penny P Easton Douglas F DF Tischkowitz Marc M Spurdle Amanda B AB Schmutzler Rita K RK Wappenschmidt Barbara B Hahnen Eric E Hooning Maartje J MJ Singer Christian F CF Wagner Gabriel G Thomassen Mads M Pedersen Inge Sokilde IS Domchek Susan M SM Nathanson Katherine L KL Lazaro Conxi C Rossing Caroline Maria CM Andrulis Irene L IL Teixeira Manuel R MR James Paul P Garber Judy J Weitzel Jeffrey N JN Jakubowska Anna A Yannoukakos Drakoulis D John Esther M EM Southey Melissa C MC Schmidt Marjanka K MK Antoniou Antonis C AC Chenevix-Trench Georgia G Blomqvist Carl C Nevanlinna Heli H

NPJ breast cancer 20200910

Germline genetic variation has been suggested to influence the survival of breast cancer patients independently of tumor pathology. We have studied survival associations of genetic variants in two etiologically unique groups of breast cancer patients, the carriers of germline pathogenic variants in BRCA1 or BRCA2 genes. We found that rs57025206 was significantly associated with the overall survival, predicting higher mortality of BRCA1 carrier patients with estrogen receptor ...[more]

PMID: 32964118

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Project description:BackgroundKnowledge is growing on the safety of assisted reproductive techniques (ART) in cancer survivors. No data exist, however, for the specific population of breast cancer patients harboring germline BRCA1/2 pathogenic variants.Patients and methodsThis is a multicenter retrospective cohort study across 30 centers worldwide including women diagnosed at ≤40 years with stage I-III breast cancer, between January 2000 and December 2012, harboring known germline BRCA1/2 pathogenic variants. Patients included in this analysis had a post-treatment pregnancy either achieved through use of ART (ART group) or naturally (non-ART group). ART procedures included ovulation induction, ovarian stimulation for in vitro fertilization or intracytoplasmic sperm injection, and embryo transfer under hormonal replacement therapy.ResultsAmong the 1424 patients registered in the study, 168 were eligible for inclusion in the present analysis, of whom 22 were in the ART group and 146 in the non-ART group. Survivors in the ART group conceived at an older age compared with those in the non-ART group (median age: 39.7 versus 35.4 years, respectively). Women in the ART group experienced more delivery complications compared with those in the non-ART group (22.1% versus 4.1%, respectively). No other apparent differences in obstetrical outcomes were observed between cohorts. The median follow-up from pregnancy was 3.4 years (range: 0.8-8.6 years) in the ART group and 5.0 years (range: 0.8-17.6 years) in the non-ART group. Two patients (9.1%) in the ART group experienced a disease-free survival event (specifically, a locoregional recurrence) compared with 40 patients (27.4%) in the non-ART group. In the ART group, no patients deceased compared with 10 patients (6.9%) in the non-ART group.ConclusionThis study provides encouraging safety data on the use of ART in breast cancer survivors harboring germline pathogenic variants in BRCA1/2, when natural conception fails or when they opt for ART in order to carry out preimplantation genetic testing.

Project description:BackgroundGenetic testing is widespread among breast cancer patients; however, no guideline recommends using germline genetic testing results to select a chemotherapy regimen. It is unknown whether breast cancer patients who carry pathogenic variants (PVs) in BRCA1 and/or 2 (BRCA1/2) or other cancer-associated genes receive different chemotherapy regimens than noncarriers.MethodsWe linked Surveillance, Epidemiology, and End Results registry records from Georgia and California to germline genetic testing results from 4 clinical laboratories. Patients who 1) had stages I-III breast cancer, either hormone receptor (HR) positive and HER2 negative or triple negative (TNBC), diagnosed in 2013-2017; 2) received chemotherapy; and 3) were linked to genetic results were included. Chemotherapy details were extracted from Surveillance, Epidemiology, and End Results text fields completed by registrars. We examined whether PV carriers received more intensive regimens (HR-positive,HER2-negative: ≥3 drugs including an anthracycline; TNBC: ≥4 drugs including an anthracycline and platinum) and/or less standard breast cancer agents (a platinum). All statistical tests were 2-sided.ResultsAmong 2293 patients, 1451 had HR-positive, HER2-negative disease, and 842 had TNBC. On multivariable analysis of women with HR-positive, HER2-negative disease, receipt of a more intensive chemotherapy regimen varied statistically significantly by genetic results (P = .02), with platinum receipt more common among BRCA1/2 PV carriers (odds ratio = 2.44, 95% confidence interval = 1.36 to 4.38; P < .001). Among women with TNBC, chemotherapy agents did not vary significantly by genetic results.ConclusionBRCA1/2 PV carriers with HR-positive, HER2-negative breast cancer had twofold higher odds than noncarriers of receiving a platinum, as part of a more intensive chemotherapy regimen. This likely represents overtreatment and emphasizes the need to monitor how genetic testing results are managed in oncology practice.

Dataset Information

Association of germline variation with the survival of women with BRCA1/2 pathogenic variants and breast cancer.

Publications

Association of germline variation with the survival of women with <i>BRCA1/2</i> pathogenic variants and breast cancer.

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