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

Olivier Brouckaert, Anja Rudolph, Annouschka Laenen, Renske Keeman, Manjeet K. Bolla, Qin Wang, Adelheid Soubry, Hans Wildiers, Irene L. Andrulis, Volker Arndt, Matthias W. Beckmann, Javier Benitez, Carl Blomqvist, Stig E. Bojesen, Hiltrud Brauch, Paul Brennan, Hermann Brenner, Georgia Chenevix-Trench, Ji Yeob Choi, Sten CornelissenFergus J. Couch, Angela Cox, Simon S. Cross, Kamila Czene, Mikael Eriksson, Peter A. Fasching, Jonine Figueroa, Henrik Flyger, Graham G. Giles, Anna González-Neira, Pascal Guénel, Per Hall, Antoinette Hollestelle, John L. Hopper, Hidemi Ito, Michael Jones, Daehee Kang, kConFab Investigators, Julia A. Knight, Veli Matti Kosma, Jingmei Li, Annika Lindblom, Jenna Lilyquist, Artitaya Lophatananon, Arto Mannermaa, Siranoush Manoukian, Sara Margolin, Keitaro Matsuo, Kenneth Muir, Heli Nevanlinna, Paolo Peterlongo, Katri Pylkäs, Suleeporn Saajrang, Caroline Seynaeve, Chen Yang Shen, Xiao Ou Shu, Melissa C. Southey, Anthony Swerdlow, Soo Hwang Teo, Rob A.E.M. Tollenaar, Thérèse Truong, Chiu chen Tseng, Alexandra J. van den Broek, Carolien H.M. van Deurzen, Robert Winqvist, Anna H. Wu, Cheng Har Yip, Jyh Cherng Yu, Wei Zheng, Roger L. Milne, Paul D.P. Pharoah, Douglas F. Easton, Marjanka K. Schmidt, Montserrat Garcia-Closas, Jenny Chang-Claude, Diether Lambrechts, Patrick Neven

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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 < 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.

Original languageEnglish
Article number119
Number of pages12
JournalBreast Cancer Research
Volume19
Issue number1
DOIs
Publication statusPublished - 7 Nov 2017
Externally publishedYes

Keywords

  • Age at breast cancer diagnosis
  • Age at first full-time pregnancy
  • Age at menarche
  • Breast cancer subtype
  • Parity

Cite this

Brouckaert, O., Rudolph, A., Laenen, A., Keeman, R., Bolla, M. K., Wang, Q., Soubry, A., Wildiers, H., Andrulis, I. L., Arndt, V., Beckmann, M. W., Benitez, J., Blomqvist, C., Bojesen, S. E., Brauch, H., Brennan, P., Brenner, H., Chenevix-Trench, G., Choi, J. Y., ... Neven, P. (2017). Reproductive profiles and risk of breast cancer subtypes: A multi-center case-only study. Breast Cancer Research, 19(1), [119]. https://doi.org/10.1186/s13058-017-0909-3