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

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Peer-reviewed

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Article

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Authors

Brouckaert, Olivier 
Rudolph, Anja 
Laenen, Annouschka 
Keeman, Renske 
Bolla, Manjeet K 

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 28095 invasive BC patients 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 on BC subtype risk was also tested, across all ages and, because age was modeled nonlinearly, specifically at age 35, 55 and 75. 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; Pinteraction 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-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.

Description

Keywords

kConFab, Humans, Breast Neoplasms, Reproductive History, Odds Ratio, Risk Assessment, Risk Factors, Cohort Studies, Adult, Aged, Middle Aged, Female, Young Adult, Triple Negative Breast Neoplasms, Biomarkers, Tumor

Journal Title

Breast cancer research : BCR

Conference Name

Journal ISSN

1465-5411
1465-542X

Volume Title

19

Publisher

Springer Nature
Sponsorship
EC FP7 CP (223175)
Cancer Research UK (CRUK-A12014)
Cancer Research UK (CRUK-A10118)
Wellcome Trust (203477/Z/16/Z)