• breast cancer;
  • women;
  • risk factors;
  • cohort study;
  • estrogen receptor;
  • hormone receptor;
  • postmenopausal women;
  • premenopausal women;
  • attributable fraction;
  • hormone replacement therapy;
  • birth weight

Breast cancer is the most frequently diagnosed cancer among women worldwide. Breast cancer risk factors have been widely explored individually; however, little is known about their combined impact. We included 67,634 women from the French E3N prospective cohort, aged 42–72 at baseline. During a 15-year follow-up period, 497 premenopausal and 3,138 postmenopausal invasive breast cancer cases were diagnosed. Population-attributable fractions (PAFs) were used to estimate cases proportions attributable to risk factors under hypothetical scenarios of lowest exposure. We examined overall premenopausal and postmenopausal invasive breast cancers and tumour subtypes (ER status and HER2 expression). Premenopausal breast cancer was not significantly attributable to non-behavioral (61.2%, −15.5 to 91.88%) nor to behavioral (39.9%, −71.0 to 93.9%) factors, contrary to postmenopausal breast cancer (41.9%, 4.5 to 68.7% and 53.5%, 12.8 to 78.7%, respectively). Individually, the highest statistically significant PAFs were obtained in premenopause for birth weight (33.6%, 5.7 to 56.6%) and age at menarche (19.8%, 5.2 to 33.6%) for non-behavioral factors and in postmenopause for history of benign breast diseases (14.9%, 11.6 to 18.0%) and age at menarche (9.7%, 3.9 to 15.5%) for non-behavioral factors and for body shape at menarche (17.1%, 9.7 to 24.3%), use of hormone replacement therapy (14.5%, 9.2 to 19.6%), dietary pattern (10.1%, 2.6 to 17.4%) and alcohol consumption (5.6%, 1.9 to 9.3%) for behavioral factors. These proportions were higher for ER+, HER2− and ER+/HER2− postmenopausal breast cancers. Our data support the hypothesis that in postmenopause, never starting unhealthy behaviors can reduce the number of diagnosed breast cancers.