Reproductive profiles and risk of breast cancer subtypes: a multi-center case-only study

Journal article

Publication Details

Author(s): Brouckaert O, Rudolph A, Laenen A, Keeman R, Bolla MK, Wang Q, Soubry A, Wildiers H, Andrulis IL, Arndt V, Beckmann M, Benitez J, Blomqvist C, Bojesen SE, Brauch H, Brennan P, Brenner H, Chenevix-Trench G, Choi JY, Cornelissen S, Couch FJ, Cox A, Cross SS, Czene K, Eriksson M, Fasching P, Figueroa J, Flyger H, Giles GG, Gonzalez-Neira A, Guenel P, Hall P, Hollestelle A, Hopper JL, Ito H, Jones M, Kang D, Knight JA, Kosma VM, Li J, Lindblom A, Lilyquist J, Lophatananon A, Mannermaa A, Manoukian S, Margolin S, Matsuo K, Muir K, Nevanlinna H, Peterlongo P, Pylkas K, Saajrang S, Seynaeve C, Shen CY, Shu XO, Southey MC, Swerdlow A, Teo SH, Tollenaar RAEM, Truong T, Tseng CC, Van Den Broek AJ, Van Deurzen CHM, Winqvist R, Wu AH, Yip CH, Yu JC, Zheng W, Milne RL, Pharoah PDP, Easton DF, Schmidt MK, Garcia-Closas M, Chang-Claude J, Lambrechts D, Neven P
Journal: Breast Cancer Research
Publication year: 2017
Volume: 19
Journal issue: 1
ISSN: 1465-542X


BACKGROUND: Previous studies have shown that reproductive factors are differentially associated with breast cancer (BC) risk by subtypes. The aim of this study was to investigate associations between reproductive factors and BC subtypes, and whether these vary by age at diagnosis.
METHODS: We used pooled data on tumor markers (estrogen and progesterone receptor, human epidermal growth factor receptor-2 (HER2)) and reproductive risk factors (parity, age at first full-time pregnancy (FFTP) and age at menarche) from 28,095 patients with invasive BC from 34 studies participating in the Breast Cancer Association Consortium (BCAC). In a case-only analysis, we used logistic regression to assess associations between reproductive factors and BC subtype compared to luminal A tumors as a reference. The interaction between age and parity in BC subtype risk was also tested, across all ages and, because age was modeled non-linearly, specifically at ages 35, 55 and 75 years.
RESULTS: Parous women were more likely to be diagnosed with triple negative BC (TNBC) than with luminal A BC, irrespective of age (OR for parity = 1.38, 95% CI 1.16-1.65, p = 0.0004; p for interaction with age = 0.076). Parous women were also more likely to be diagnosed with luminal and non-luminal HER2-like BCs and this effect was slightly more pronounced at an early age (p for interaction with age = 0.037 and 0.030, respectively). For instance, women diagnosed at age 35 were 1.48 (CI 1.01-2.16) more likely to have luminal HER2-like BC than luminal A BC, while this association was not significant at age 75 (OR = 0.72, CI 0.45-1.14). While age at menarche was not significantly associated with BC subtype, increasing age at FFTP was non-linearly associated with TNBC relative to luminal A BC. An age at FFTP of 25 versus 20 years lowered the risk for TNBC (OR = 0.78, CI 0.70-0.88, p < 0.0001), but this effect was not apparent at a later FFTP.
CONCLUSIONS: Our main findings suggest that parity is associated with TNBC across all ages at BC diagnosis, whereas the association with luminal HER2-like BC was present only for early onset BC.

FAU Authors / FAU Editors

Beckmann, Matthias Prof. Dr.
Lehrstuhl für Geburtshilfe und Frauenheilkunde
Fasching, Peter PD Dr.
Professur für Translationale Frauenheilkunde und Geburtshilfe

External institutions with authors

Aichi Cancer Center Research Institute
Antoni van Leeuwenhoek
Cancer Council Victoria
Cancer Research Initiatives Foundation (CARIF)
China Medical University (CMU) / 中國醫藥大學
Copenhagen University Hospital
Deutsches Krebsforschungszentrum (DKFZ)
Erasmus University Medical Center
Erasmus University Rotterdam (EUR) / Erasmus Universiteit Rotterdam
Flanders Institute for Biotechnology / Vlaams Instituut voor Biotechnologie (VIB)
Fondazione IRCCS: Istituto Nazionale dei Tumori
Helsingin yliopisto / University of Helsinki
IFOM - FIRC Institute of Molecular Oncology
International Agency for Research on Cancer (IARC)
Jan Yperman Ziekenhuis
Karolinska Institute
Katholieke Universiteit Leuven (KUL) / Catholic University of Leuven
Leiden University
Mayo Clinic
Mount Sinai Hospital (MSH)
National Cancer Institute (NCI)
National Taiwan University Hospital (NTUH) / 國立台灣大學醫學院附設醫院
Netherlands Cancer Institute (NKI)
Oulun Yliopisto / University of Oulo
QIMR Berghofer Medical Research Institute (früher: the Queensland Institute of Medical Research)
Seoul National University (SNU) / 서울대학교
Spanish National Cancer Research Centre / Centro Nacional de Investigaciones Oncológicas (CNIO)
The Institute of Cancer Research (ICR)
The University of Melbourne
University Hospital Leuven (UZ) / Universitaire ziekenhuizen Leuven
University of Cambridge
University of Eastern Finland
University of Edinburgh
University of Malaya (UM) / Universiti Malaya
University of Paris 11 - Paris-Sud / Université Paris XI Paris-Sud
University of Sheffield
University of Southern California (USC)
University of Warwick
Vanderbilt University

How to cite

Brouckaert, O., Rudolph, A., Laenen, A., Keeman, R., Bolla, M.K., Wang, Q.,... Neven, P. (2017). Reproductive profiles and risk of breast cancer subtypes: a multi-center case-only study. Breast Cancer Research, 19(1).

Brouckaert, Olivier, et al. "Reproductive profiles and risk of breast cancer subtypes: a multi-center case-only study." Breast Cancer Research 19.1 (2017).


Last updated on 2019-26-03 at 07:38