TY - JOUR

T1 - Reproductive profiles and risk of breast cancer subtypes

T2 - A multi-center case-only study

AU - Brouckaert, Olivier

AU - Rudolph, Anja

AU - Laenen, Annouschka

AU - Keeman, Renske

AU - Bolla, Manjeet K.

AU - Wang, Qin

AU - Soubry, Adelheid

AU - Wildiers, Hans

AU - Andrulis, Irene L.

AU - Arndt, Volker

AU - Beckmann, Matthias W.

AU - Benitez, Javier

AU - Blomqvist, Carl

AU - Bojesen, Stig E.

AU - Brauch, Hiltrud

AU - Brennan, Paul

AU - Brenner, Hermann

AU - Chenevix-Trench, Georgia

AU - Choi, Ji Yeob

AU - Cornelissen, Sten

AU - Couch, Fergus J.

AU - Cox, Angela

AU - Cross, Simon S.

AU - Czene, Kamila

AU - Eriksson, Mikael

AU - Fasching, Peter A.

AU - Figueroa, Jonine

AU - Flyger, Henrik

AU - Giles, Graham G.

AU - González-Neira, Anna

AU - Guénel, Pascal

AU - Hall, Per

AU - Hollestelle, Antoinette

AU - Hopper, John L.

AU - Ito, Hidemi

AU - Jones, Michael

AU - Kang, Daehee

AU - kConFab

AU - Knight, Julia A.

AU - Kosma, Veli Matti

AU - Li, Jingmei

AU - Lindblom, Annika

AU - Lilyquist, Jenna

AU - Lophatananon, Artitaya

AU - Mannermaa, Arto

AU - Manoukian, Siranoush

AU - Margolin, Sara

AU - Matsuo, Keitaro

AU - Muir, Kenneth

AU - Nevanlinna, Heli

AU - Peterlongo, Paolo

AU - Change-Claude, Jenny

AU - Lambrechts, Diether

AU - Neven, Patrick

PY - 2017/11/7

Y1 - 2017/11/7

N2 - 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.

AB - 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.

KW - Age at breast cancer diagnosis

KW - Age at first full-time pregnancy

KW - Age at menarche

KW - Breast cancer subtype

KW - Parity

U2 - 10.1186/s13058-017-0909-3

DO - 10.1186/s13058-017-0909-3

M3 - Journal article

C2 - 29116004

AN - SCOPUS:85033407313

VL - 19

JO - Breast Cancer Research

JF - Breast Cancer Research

SN - 1465-5411

M1 - 119

ER -