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

Brouckaert O 1 , Rudolph A 2 , Laenen A 3 , Keeman R 4 , Bolla MK 5 , Wang Q 5 Show all authors , Soubry A 6 , Wildiers H 7 , Andrulis IL 8 , Arndt V 9 , Beckmann MW 10 , Benitez J 11 , Blomqvist C 12 , Bojesen SE 13 , Brauch H 14 , Brennan P 15 , Brenner H 9 , Chenevix-Trench G 16 , Choi JY 17 , Cornelissen S 4 , Couch FJ 18 , Cox A 19 , Cross SS 20 , Czene K 21 , Eriksson M 21 , Fasching PA 10 , Figueroa J 22 , Flyger H 23 , Giles GG 24 , González-Neira A 11 , Guénel P 25 , Hall P 21 , Hollestelle A 26 , Hopper JL 27 , Ito H 28 , Jones M 29 , Kang D 17 , kConFab , Knight JA 30 , Kosma VM 31 , Li J 21 , Lindblom A 32 , Lilyquist J 33 , Lophatananon A 34 , Mannermaa A 31 , Manoukian S 35 , Margolin S 36 , Matsuo K 37 , Muir K 34 , Nevanlinna H 38 , Peterlongo P 39 , Pylkäs K 40 , Saajrang S 41 , Seynaeve C 26 , Shen CY 42 , Shu XO 43 , Southey MC 44 , Swerdlow A 29 , Teo SH 45 , Tollenaar RAEM 46 , Truong T 25 , Tseng CC 47 , van den Broek AJ 48 , van Deurzen CHM 49 , Winqvist R 40 , Wu AH 47 , Yip CH 50 , Yu JC 51 , Zheng W 52 , Milne RL 24 , Pharoah PDP 5 , Easton DF 5 , Schmidt MK 4 , Garcia-Closas M 53 , Chang-Claude J 2 , Lambrechts D 54 , Neven P 7

Affiliations 

  • 1 Department of Obstetrics and Gynaecology, Jan Yperman Hospital, Ypres, Belgium
  • 2 Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
  • 3 Centre for Biostatistics and Statistical Bioinformatics, KU Leuven, Leuven, Belgium
  • 4 Netherlands Cancer Institute, Antoni van Leeuwenhoek hospital, Amsterdam, The Netherlands
  • 5 Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care University of Cambridge, Cambridge, UK
  • 6 Epidemiology Research Unit, Department of Public Health and Primary Care, Faculty of Medicine, KU Leuven - University of Leuven, Leuven, Belgium
  • 7 Department of Oncology, Leuven Multidisciplinary Breast Cancer, University Hospital Leuven, KU Leuven, Leuven, Belgium
  • 8 Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Canada
  • 9 Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
  • 10 Department of Gynaecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany
  • 11 Human Cancer Genetics Program, Spanish National Cancer Research Centre, Madrid, Spain
  • 12 Department of Oncology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland
  • 13 Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark
  • 14 Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, Germany
  • 15 International Agency for Research on Cancer, Lyon, France
  • 16 Department of Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Australia
  • 17 Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea
  • 18 Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA
  • 19 Sheffield Cancer Research, Department of Oncology and Metabolism, University of Sheffield, Sheffield, UK
  • 20 Academic Unit of Pathology, Department of Neuroscience, University of Sheffield, Sheffield, UK
  • 21 Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
  • 22 Usher Institute of Population Health Sciences and Informatics, The University of Edinburgh Medical School, Edinburgh, UK
  • 23 Department of Breast Surgery, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark
  • 24 Cancer Epidemiology & Intelligence Division, Cancer Council Victoria, Melbourne, Australia
  • 25 Cancer & Environment Group, Center for Research in Epidemiology and Population Health (CESP), INSERM, University Paris-Sud, University Paris-Saclay, Villejuif, France
  • 26 Department of Medical Oncology, Family Cancer Clinic, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
  • 27 Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global health, The University of Melbourne, Melbourne, Australia
  • 28 Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan
  • 29 Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK
  • 30 Prosserman Centre for Health Research, Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Canada
  • 31 Cancer Center of Eastern Finland, University of Eastern Finland, Kuopio, Finland
  • 32 Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
  • 33 Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA
  • 34 Division of Health Sciences, Warwick Medical School, Warwick University, Coventry, UK
  • 35 Unit of Medical Genetics, Department of Preventive and Predictive Medicine, Fondazione IRCCS (Istituto Di Ricovero e Cura a Carattere Scientifico) Istituto Nazionale dei Tumori (INT), Milan, Italy
  • 36 Department of Oncology - Pathology, Karolinska Institutet, Stockholm, Sweden
  • 37 Division of Molecular Medicine, Aichi Cancer Center Research Institute, Nagoya, Japan
  • 38 Department of Obstetrics and Gynecology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland
  • 39 IFOM, The FIRC (Italian Foundation for Cancer Research) Institute of Molecular Oncology, Milan, Italy
  • 40 Laboratory of Cancer Genetics and Tumor Biology, Cancer and Translational Medicine Research Unit, Biocenter Oulu, University of Oulu, Oulu, Finland
  • 41 National Cancer Institute, Bangkok, Thailand
  • 42 School of Public Health, China Medical University, Taichung, Taiwan
  • 43 Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA
  • 44 Department of Pathology, The University of Melbourne, Melbourne, Australia
  • 45 Cancer Research Initiatives Foundation, Subang Jaya, Selangor, Malaysia
  • 46 Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
  • 47 Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
  • 48 Division of Psychosocial Research and Epidemiology, Netherlands Cancer Institute, Amsterdam, The Netherlands
  • 49 Department of Pathology, Erasmus University Medical Center, Rotterdam, The Netherlands
  • 50 Breast Cancer Research Unit, Cancer Research Institute, University Malaya Medical Centre, Kuala Lumpur, Malaysia
  • 51 Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan
  • 52 Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA
  • 53 Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA
  • 54 Center for Cancer Biology, VIB, Leuven, Belgium. Diether.Lambrechts@vib-kuleuven.be
Breast Cancer Res, 2017 Nov 07;19(1):119.
PMID: 29116004 DOI: 10.1186/s13058-017-0909-3

Abstract

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 

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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