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

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Authors
Brouckaert, Olivier; Rudolph, Anja; Laenen, Annouschka; Keeman, Renske; Bolla, Manjeet K.; Wang, Qin; Soubry, Adelheid; Wildiers, Hans; Andrulis, Irene L.; Arndt, Volker; Beckmann, Matthias W.; Benitez, Javier; Blomqvist, Carl; Bojesen, Stig E.; Brauch, Hiltrud; Brennan, Paul; Brenner, Hermann; Chenevix-Trench, Georgia; Choi, Ji-Yeob; Cornelissen, Sten; Couch, Fergus J.; Cox, Angela; Cross, Simon S.; Czene, Kamila; Eriksson, Mikael; Fasching, Peter A.; Figueroa, Jonine; Flyger, Henrik; Giles, Graham G.; González-Neira, Anna; Guénel, Pascal; Hall, Per; Hollestelle, Antoinette; Hopper, John L.; Ito, Hidemi; Jones, Michael; Kang, Daehee; Knight, Julia A.; Kosma, Veli-Matti; Li, Jingmei; Lindblom, Annika; Lilyquist, Jenna; Lophatananon, Artitaya; Mannermaa, Arto; Manoukian, Siranoush; Margolin, Sara; Matsuo, Keitaro; Muir, Kenneth; Nevanlinna, Heli; Peterlongo, Paolo; Pylkäs, Katri; Saajrang, Suleeporn; Seynaeve, Caroline; Shen, Chen-Yang; Shu, Xiao-Ou; Southey, Melissa C.; Swerdlow, Anthony; Teo, Soo-Hwang; Tollenaar, Rob A. E. M.; Truong, Thérèse; Tseng, Chiu-chen; van den Broek, Alexandra J.; van Deurzen, Carolien H. M.; Winqvist, Robert; Wu, Anna H.; Yip, Cheng H.; Yu, Jyh-Cherng; Zheng, Wei; Milne, Roger L.; Pharoah, Paul D. P.; Easton, Douglas F.; Schmidt, Marjanka K.; Garcia-Closas, Montserrat; Chang-Claude, Jenny; Lambrechts, Diether; Neven, Patrick
Issue Date
2017-11-07
Publisher
BioMed Central
Citation
Breast Cancer Research, 19(1):119
Keywords
Breast cancer subtypeAge at breast cancer diagnosisParityAge at first full-time pregnancyAge at menarche
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.
ISSN
1465-542X
Language
English
URI
http://hdl.handle.net/10371/138397
DOI
https://doi.org/10.1186/s13058-017-0909-3
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College of Medicine/School of Medicine (의과대학/대학원)Dept. of Biomedical Sciences (대학원 의과학과)Journal Papers (저널논문_의과학과)
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