Article open access publication

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

Breast Cancer Research, Springer Nature, ISSN 1465-5411

Volume 19, 1, 2017

DOI:10.1186/s13058-017-0909-3, Dimensions: pub.1092578278, PMC: PMC5688822, PMID: 29116004,


Wang, Qin (5)
Benitez, Javier (10) (11)
Bojesen, Stig E. (13) (14) (15)
Brauch, Hiltrud (2) (16) (17)
Figueroa, Jonine (25) (26)
Giles, Graham G (28) (29)
Hall, Per (23)
kConFab (34)
Knight, Julia A. (8) (35)
Kosma, Veli-Matti (36) (37)
Mannermaa, Arto (36) (37)
Muir, Kenneth (38) (39)
Pylkäs, Katri (43) (44)
Shen, Chen-Yang (46) (47)
Teo, Soo-Hwang (49) (50)
Winqvist, Robert (43) (44)
Wu, Anna H (52)
Zheng, Wei (54)
Milne, Roger L. (28) (29)
Lambrechts, Diether * (3) (56)

* Corresponding author



  1. (1) Department of Obstetrics and Gynaecology, Jan Yperman Hospital, Ypres, Belgium
  2. (2) German Cancer Research Center, grid.7497.d
  3. (3) KU Leuven, grid.5596.f
  4. (4) Antoni van Leeuwenhoek Hospital, grid.430814.a
  5. (5) University of Cambridge, grid.5335.0
  6. (6) Department of Oncology, Leuven Multidisciplinary Breast Cancer, University Hospital Leuven, KU Leuven, Leuven, Belgium
  7. (7) Lunenfeld-Tanenbaum Research Institute, grid.250674.2
  8. (8) University of Toronto, grid.17063.33
  9. (9) Department of Gynaecology and Obstetrics, University Hospital Erlangen, Friedrich Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany
  10. (10) Centro de Investigación en Red de Enfermedades Raras, Valencia, Spain
  11. (11) Spanish National Cancer Research Centre, grid.7719.8
  12. (12) Department of Oncology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland
  13. (13) Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark
  14. (14) Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark
  15. (15) University of Copenhagen, grid.5254.6, KU
  16. (16) Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, grid.502798.1
  17. (17) University of Tübingen, grid.10392.39
  18. (18) International Agency For Research On Cancer, grid.17703.32
  19. (19) QIMR Berghofer Medical Research Institute, grid.1049.c
  20. (20) Seoul National University, grid.31501.36
  21. (21) Mayo Clinic, grid.66875.3a
  22. (22) University of Sheffield, grid.11835.3e
  23. (23) Karolinska Institute, grid.4714.6
  24. (24) University of California, Los Angeles, grid.19006.3e
  25. (25) University of Edinburgh, grid.4305.2
  26. (26) National Cancer Institute, grid.48336.3a
  27. (27) Department of Breast Surgery, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark
  28. (28) University of Melbourne, grid.1008.9
  29. (29) Cancer Council Victoria, grid.3263.4
  30. (30) Cancer & Environment Group, Center for Research in Epidemiology and Population Health (CESP), INSERM, University Paris-Sud, University Paris-Saclay, Villejuif, France
  31. (31) Erasmus University Medical Center, grid.5645.2
  32. (32) Aichi Cancer Center, grid.410800.d
  33. (33) Institute of Cancer Research, grid.18886.3f
  34. (34) kConFab, Research Department, Peter MacCallum Cancer Centre, and The Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Australia
  35. (35) Mount Sinai Hospital, grid.416166.2
  36. (36) Kuopio University Hospital, grid.410705.7
  37. (37) University of Eastern Finland, grid.9668.1
  38. (38) University of Manchester, grid.5379.8
  39. (39) University of Warwick, grid.7372.1
  40. (40) Fondazione IRCCS Istituto Nazionale dei Tumori, grid.417893.0
  41. (41) Department of Obstetrics and Gynecology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland
  42. (42) IFOM, The FIRC (Italian Foundation for Cancer Research) Institute of Molecular Oncology, Milan, Italy
  43. (43) Laboratory of Cancer Genetics and Tumor Biology, Northern Finland Laboratory Centre Oulu, Oulu, Finland
  44. (44) University of Oulu, grid.10858.34
  45. (45) National Cancer Institute of Thailand, grid.419173.9
  46. (46) China Medical University, grid.254145.3
  47. (47) Institute of Biomedical Sciences, Academia Sinica, grid.482251.8
  48. (48) Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA
  49. (49) Cancer Research Initiatives Foundation, grid.427737.2
  50. (50) University Malaya Medical Centre, grid.413018.f
  51. (51) Leiden University Medical Center, grid.10419.3d
  52. (52) University of Southern California, grid.42505.36
  53. (53) National Taiwan University Hospital, grid.412094.a
  54. (54) Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA
  55. (55) University Cancer Center Hamburg, grid.412315.0
  56. (56) Flanders Institute for Biotechnology, grid.11486.3a


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.


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Times Cited: 13

Field Citation Ratio (FCR): 4.07

Relative Citation ratio (RCR): 1.12

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