Association between breast cancer risk factors and molecular type in postmenopausal patients with hormone receptor-positive early breast cancer
Evidence shows that genetic and non-genetic risk factors for breast cancer (BC) differ relative to the molecular subtype. This analysis aimed to investigate associations between epidemiological risk factors and immunohistochemical subtypes in a cohort of postmenopausal, hormone receptor-positive BC patients.
The prospective, single-arm, multicenter phase IV PreFace study (Evaluation of Predictive Factors Regarding the Effectivity of Aromatase Inhibitor Therapy) included 3529 postmenopausal patients with hormone receptor-positive early BC. Data on their epidemiological risk factors were obtained from patients’ diaries and their medical histories. Data on estrogen receptor, progesterone receptor, and HER2 receptor status were obtained from pathology reports. Patients with incomplete information were excluded. Data were analyzed using conditional inference regression analysis, analysis of variance, and the chi-squared test.
In a cohort of 3392 patients, the strongest association with the molecular subtypes of BC was found for hormone replacement therapy (HRT) before diagnosis of early BC. The analysis showed that patients who took HRT at diagnosis had luminal A-like BC more often (83.7%) than those who had never taken HRT or had stopped taking it (75.5%). Luminal B-like BC and HER2-positive BC were diagnosed more often in women who had never taken HRT or had stopped taking it (13.3% and 11.2%, respectively) than in women who were taking HRT at diagnosis of BC (8.3% and 8.0%, respectively).
This analysis shows an association between HRT and the distribution of molecular subtypes of BC. However, no associations between other factors (e.g., age at diagnosis, body mass index, smoking status, age at menopause, number of deliveries, age at first delivery, breastfeeding history, or family history) were noted.
KeywordsBreast cancer Molecular subtype Risk factors Hormone replacement therapy Prognosis
MW, JP, PAF, and CR contributed to the acquisition and interpretation of data, to the conception, drafting, and critical revision of the manuscript. CF and LH performed statistical analyses and contributed to critical revision of the manuscript. SYB, BV, AH, AH, SMJ, MPL, WJ, CRL, ADH, CBW, GB, AF, WM, RW, NH, OH, SK, BM, CT, HG, CW, CMB, CCH, KA, PG, FH, TFB, NN, CL, HCK, PK, MW, DSB, AK, CB, VS, GF, VP, DW, BR, TF, AR, NM, and MWB were involved in the acquisition of patient and tumor data and in critical revision of the manuscript. All authors have read the manuscript and have given their final approval for publication of this study.
This work was supported in part by Novartis Pharma GmbH Germany.
Compliance with ethical standards
Conflict of interest
A Hartmann received honoraria from BMS, Roche, MSD, Novartis, AstraZeneca, NanoString, and BioNTech and funding from NanoString, BioNTech, and Janssen-Cilag. MPL received honoraria from Pfizer, Roche, MSD, Hexal, Novartis, AstraZeneca, Celgene, Eisai, Medac, and Thieme for advisory boards, lectures, and travel support. WJ received research grants from Novartis. ADH participated on advisory boards for Novartis. RW participated on advisory boards for Novartis, AstraZeneca, Pfizer, and Lilly. SK participated on advisory boards for Roche/Genentech, Genomic Health, Novartis, AstraZeneca, Amgen, Celgene, SOMATEX, Daiichi Sankyo, Puma Biotechnology, pfm medical, Pfizer, and MSD Oncology and received funding from Roche and Daiichi Sankyo. CT received honoraria from Amgen, AstraZeneca, Celgene, Genomic Health, Lilly, NanoString, Novartis, Pfizer, Puma, and Roche for lectures and advisory boards. CCH received honoraria from Roche. PG received honoraria from Novartis, Roche, and PharmaMar. NN received honoraria from Janssen-Cilag and Novartis. HCK received honoraria from Carl Zeiss Meditec, TEVA, Theraclion, Novartis, Amgen, AstraZeneca, Pfizer, Janssen-Cilag, GSK, LIV Pharma, Roche, and Genomic Health and is stock owner of Theraclion and Phaon Scientific GmbH. MW participated on advisory boards for Novartis, Roche, Pfizer, and Celgene. BR participated on advisory boards for Novartis and Roche and received funding from AstraZeneca, Chugai, Lilly, Novartis, Janssen-Cilag, and Sanofi Aventis. TF participated on advisory boards for Novartis, Roche, AstraZeneca, Pfizer, and Daiichi Sankyo. MWB’s institution received research grants from Novartis. PAF received honoraria from Novartis, Roche, Pfizer, and Amgen. CR received honoraria from Novartis, Roche, Celgene, and Eisai. All remaining authors have declared no conflicts of interest.
Approval for the study was obtained from the ethics committee of the Faculty of Medicine at Friedrich Alexander University of Erlangen-Nuremberg and all of the relevant local ethics committees. All procedures were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
Written informed consent was obtained from the patients as part of the inclusion criteria before they entered the study.
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