Vitamin D Supplements May Reduce MHT-Associated Breast Cancer Risk: Evidence From The E3N Cohort

Claire CADEAU, Inserm, France
FAGHERAZZI G. 1,2 , BOUTRON-RUAULT M. 1,2 , MESRINE S. 1,2 , CLAVEL-CHAPELON F. 1,2 , FOURNIER A. 1,2

1 Generations and Health Team, U1018, Inserm, Villejuif, France
2 Gustave Roussy, Villejuif, France

Purpose: The high prevalence of vitamin D inadequacy in Europe and in North America has raised concern about potential adverse health effects of vitamin D deficiency. Experimental studies support protective effects of vitamin D on breast cancer, but epidemiological data remain inconclusive. Recent in vitro studies suggested potential interactions between vitamin D and estrogens. Our objective was to investigate the relationship between vitamin D supplementation and breast cancer risk, considering the recency of vitamin D supplementation and a potential interaction with menopausal hormone therapy (MHT) use.

Methods: Between 1995 and 2008, 2482 invasive breast cancers were diagnosed among 57,403 postmenopausal women from the French E3N cohort. Vitamin D supplementation was prospectively assessed from biennially self-administered questionnaires sent in 1995, 2000, 2002, and 2005. Multivariable HRs for primary invasive breast cancer and 95% CIs were estimated with Cox models.

Results: Current but not past vitamin D supplementation was associated with decreased postmenopausal breast cancer risk, compared with never use, (HR: 0.82, CI95%: [0.69, 0.97] for current use, and HR: 1.08, CI95%: [0.91, 1.30] for past use, Phomogeneity = 0.02), especially for ER+ tumours (HR: 0.73, CI95%: [0.59, 0.91]). The association with current vitamin D supplementation was modified by MHT use (Phomogeneity = 0.02): the decreased risk was restricted to MHT ever users: HR: 0.74, CI95%: [0.60, 0.90], while HR: 1.13, CI95%: [0.89, 1.56] among never users.

Conclusions: In our study, vitamin D supplementation was associated with decreased postmenopausal breast cancer risk in MHT users only. These findings should be confirmed before considering vitamin D supplementation to partly balance the MHT-associated increased breast cancer risk.

Funding source: French Ministry of Research, Fondation de France, Mutuelle générale de l’éducation nationale, European Community, Ligue Nationale Contre le Cancer, Gustave Roussy, and Institut national de la santé et de la recherche médicale.