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


METHODS
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.
Inserm, Centre for Research in Epidemiology and Population Health, Nutrition, Hormones and Women's Health Team, Villejuif Cedex, France; Université Paris-Sud, Villejuif Cedex, France; and Gustave Roussy, Villejuif Cedex, France.
Claire
C
Cadeau
Inserm, Centre for Research in Epidemiology and Population Health, Nutrition, Hormones and Women's Health Team, Villejuif Cedex, France; Université Paris-Sud, Villejuif Cedex, France; and Gustave Roussy, Villejuif Cedex, France.
Agnès
A
Fournier
Inserm, Centre for Research in Epidemiology and Population Health, Nutrition, Hormones and Women's Health Team, Villejuif Cedex, France; Université Paris-Sud, Villejuif Cedex, France; and Gustave Roussy, Villejuif Cedex, France.
Sylvie
S
Mesrine
Inserm, Centre for Research in Epidemiology and Population Health, Nutrition, Hormones and Women's Health Team, Villejuif Cedex, France; Université Paris-Sud, Villejuif Cedex, France; and Gustave Roussy, Villejuif Cedex, France.
Françoise
F
Clavel-Chapelon
Inserm, Centre for Research in Epidemiology and Population Health, Nutrition, Hormones and Women's Health Team, Villejuif Cedex, France; Université Paris-Sud, Villejuif Cedex, France; and Gustave Roussy, Villejuif Cedex, France.
Guy
G
Fagherazzi
Inserm, Centre for Research in Epidemiology and Population Health, Nutrition, Hormones and Women's Health Team, Villejuif Cedex, France; Université Paris-Sud, Villejuif Cedex, France; and Gustave Roussy, Villejuif Cedex, France marie-christine.boutron@gustaveroussy.fr.
Marie-Christine
MC
Boutron-Ruault
D000328:Adult; D000368:Aged; D015992:Body Mass Index; D001943:Breast Neoplasms / Q000453:epidemiology*; D002136:Calcium, Dietary / Q000008:administration & dosage*; D019587:Dietary Supplements; D002149:Energy Intake; D005260:Female; D005500:Follow-Up Studies; D020249:Hormone Replacement Therapy / Q000379:methods*; D006801:Humans; D015994:Incidence; D008019:Life Style; D008593:Menopause / Q000187:drug effects*; D008875:Middle Aged; D009043:Motor Activity; D015596:Nutrition Assessment; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D011795:Surveys and Questionnaires; D014807:Vitamin D / Q000008:administration & dosage*
D002136:Calcium, Dietary; D014807:Vitamin D
MHT; breast cancer; calcitriol; cohort; estrogen; menopausal hormone therapy; menopause; prospective study; supplements; vitamin D