Interaction between current vitamin D supplementation and menopausal hormone therapy use on breast cancer risk: evidence from the E3N cohort

Am J Clin Nutr. 2015 Oct;102(4):966-73. doi: 10.3945/ajcn.114.104323. Epub 2015 Sep 9.

Abstract

Background: Experimental studies suggest protective effects of vitamin D on breast carcinogenesis, particularly on estrogen receptor-positive tumors. Epidemiologic data are less conclusive.

Objective: Our objective was to investigate the association between postmenopausal breast cancer risk and current or past vitamin D supplementation overall and according to the use of menopausal hormone therapy (MHT).

Design: Between 1995 and 2008, 2482 invasive breast cancer cases were diagnosed among 57,403 postmenopausal women from the E3N prospective cohort during 581,085 person-years. Vitamin D supplementation was assessed from biennially self-administered questionnaires sent in 1995, 2000, 2002, and 2005 and from medico-administrative data on drug reimbursements since 2004. Multivariable HRs for primary invasive breast cancer and 95% CIs were estimated by using Cox models.

Results: A decreased postmenopausal breast cancer risk was associated with current (HR: 0.82; 95% CI: 0.69, 0.97) but not past (HR: 1.10; 95% CI: 0.92, 1.31) vitamin D supplementation (P-homogeneity = 0.02). The association with current vitamin D supplementation differed according to MHT use: ever users (HR: 0.74; 95% CI: 0.60, 0.90) and never users (HR: 1.13; 95% CI: 0.89, 1.56); P-homogeneity = 0.02.

Conclusions: In this observational study, current vitamin D supplementation, mostly taken daily and combined with calcium, was associated with a decreased postmenopausal breast cancer risk in MHT users. These findings should be confirmed before considering vitamin D supplementation to partly balance the MHT-associated increased breast cancer risk.

Keywords: MHT; breast cancer; calcitriol; cohort; estrogen; menopausal hormone therapy; menopause; prospective study; supplements; vitamin D.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Body Mass Index
  • Breast Neoplasms / epidemiology*
  • Calcium, Dietary / administration & dosage*
  • Dietary Supplements*
  • Energy Intake
  • Female
  • Follow-Up Studies
  • Hormone Replacement Therapy / methods*
  • Humans
  • Incidence
  • Life Style
  • Menopause / drug effects*
  • Middle Aged
  • Motor Activity
  • Nutrition Assessment
  • Proportional Hazards Models
  • Prospective Studies
  • Risk Factors
  • Surveys and Questionnaires
  • Vitamin D / administration & dosage*

Substances

  • Calcium, Dietary
  • Vitamin D