Reproductive factors and risk of hormone receptor positive and negative breast cancer: a cohort study.

Rebecca Ritte, Kaja Tikk, Annekatrin Lukanova, Anne Tjønneland, Anja Olsen, Kim Overvad, Laure Dossus, Agnès Fournier, Françoise Clavel-Chapelon, Verena Grote, Heiner Boeing, Krasimira Aleksandrova, Antonia Trichopoulou, Pagona Lagiou, Dimitrios Trichopoulos, Domenico Palli, Franco Berrino, Amalia Mattiello, Rosario Tumino, Carlotta Sacerdote, José Ramón Quirós, Genevieve Buckland, Esther Molina-Montes, María-Dolores Chirlaque, Eva Ardanaz, Pilar Amiano, H Bas Bueno-de-Mesquita, Carla H van Gils, Petra Hm Peeters, Nick Wareham, Kay-Tee Khaw, Timothy J Key, Ruth C Travis, Elisabete Weiderpass, Vanessa Dumeaux, Eliv Lund, Malin Sund, Anne Andersson, Isabelle Romieu, Sabina Rinaldi, Paulo Vineis, Melissa A Merritt, Elio Riboli, Rudolf Kaaks, BMC cancer 13, 584 (2013)
DOI
10.1186/1471-2407-13-584
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Abstract

The association of reproductive factors with hormone receptor (HR)-negative breast tumors remains uncertain.

Within the EPIC cohort, Cox proportional hazards models were used to describe the relationships of reproductive factors (menarcheal age, time between menarche and first pregnancy, parity, number of children, age at first and last pregnancies, time since last full-term childbirth, breastfeeding, age at menopause, ever having an abortion and use of oral contraceptives [OC]) with risk of ER-PR- (n = 998) and ER+PR+ (n = 3,567) breast tumors.

A later first full-term childbirth was associated with increased risk of ER+PR+ tumors but not with risk of ER-PR- tumors (≥35 vs. ≤19 years HR: 1.47 [95% CI 1.15-1.88] p(trend) < 0.001 for ER+PR+ tumors; ≥35 vs. ≤19 years HR: 0.93 [95% CI 0.53-1.65] p(trend) = 0.96 for ER-PR- tumors; P(het) = 0.03). The risk associations of menarcheal age, and time period between menarche and first full-term childbirth with ER-PR-tumors were in the similar direction with risk of ER+PR+ tumors (p(het) = 0.50), although weaker in magnitude and statistically only borderline significant. Other parity related factors such as ever a full-term birth, number of births, age- and time since last birth were associated only with ER+PR+ malignancies, however no statistical heterogeneity between breast cancer subtypes was observed. Breastfeeding and OC use were generally not associated with breast cancer subtype risk.

Our study provides possible evidence that age at menarche, and time between menarche and first full-term childbirth may be associated with the etiology of both HR-negative and HR-positive malignancies, although the associations with HR-negative breast cancer were only borderline significant.