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

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review


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  • 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 Cornelissen
  • Fergus 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
  • 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
  • kConFab
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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.

TidsskriftBreast Cancer Research
Udgave nummer1
Sider (fra-til)119
StatusUdgivet - 7 nov. 2017

ID: 52337843