A Prospective Study of Multivitamin Supplement Use and Risk of Breast Cancer

Ken Ishitani; Jennifer Lin; JoAnn E. Manson; Julie E. Buring; Shumin M. Zhang


Am J Epidemiol. 2008;167(10):1197-1206. 

In This Article


At baseline, 5,033 (13.3 percent) women had never taken multivitamin supplements, 21,784 (57.4 percent) had taken multivitamin supplements in the past, and 11,103 (29.3 percent) were taking multivitamin supplements currently.

Table 1 presents the distribution of baseline risk factors for breast cancer according to status of multivitamin supplement use. Women who were taking multivitamin supplements currently tended to be younger, leaner, or more physically active. They were also more likely to consume more calories, experience late age at menarche, experience late age at menopause, have a larger number of births, take postmenopausal hormones currently, have mammography screening, or have a personal history of hysterectomy, bilateral oophorectomy, or benign breast disease. However, they were less likely to consume alcohol or smoke cigarettes currently. Age at first birth, menopausal status, and history of a mother or a sister with breast cancer did not differ substantially according to multivitamin supplement use. Age-adjusted percentages of women who had mammography screening at 12 months were 56.2 percent, 60.0 percent, and 63.9 percent among never, past, and currents users of multivitamin supplements, respectively.

Status of multivitamin supplement use was not significantly associated with risk of breast cancer among all women in the model adjusted for age and randomized treatment assignment ( Table 2 ). Additional adjustment for risk factors for breast cancer did not materially change the results; the multivariable relative risks were 0.97 (95 percent confidence interval (CI): 0.81, 1.16) for past users and 0.99 (95 percent CI: 0.82, 1.19) for current users. The results were also not appreciably changed after excluding breast cancer cases diagnosed within the first 2 years of follow-up and additionally controlling for mammographic screening, which was asked on the 12-month questionnaire; the multivariable relative risks were 1.00 (95 percent CI: 0.81, 1.22) for past users and 1.01 (95 percent CI: 0.82, 1.25) for current users. There were also no significant associations between duration or frequency of current use of multivitamin supplements and risk of breast cancer, even for those who used them currently at baseline for 20 or more years (multivariable relative risk (RR) = 1.00, 95 percent CI: 0.74, 1.35) or had taken them six or more times per week (multivariable RR = 1.00, 95 percent CI: 0.86, 1.16). The multivariable relative risk was 0.81 (95 percent CI: 0.59, 1.10) for current use of Centrum (including Centrum Silver; Wyeth Consumer Healthcare, Richmond, Virginia), the most frequently consumed multivitamin supplements among current users (18 percent). Other brands were used too infrequently to be analyzed individually.

Although the test for interaction between multivitamin supplement use and breast cancer risk according to levels of alcohol intake was not significant (p for interaction = 0.69), use of multivitamin supplements was nonsignificantly inversely associated with risk of breast cancer among women who consumed ≥10 g/day of alcohol (multivariable RR = 0.81, 95 percent CI: 0.54, 1.21 for past users; multivariable RR = 0.78, 95 percent CI: 0.50, 1.20 for current users) ( Table 3 ). There was no association between multivitamin use and breast cancer risk among women consuming <10 g/day of alcohol ( Table 3 ). When multivitamin supplement use and alcohol intake were evaluated in combination, multivitamin use appeared to reduce the increased risk of breast cancer associated with higher alcohol intake (Figure 1). The association between multivitamin supplement use and breast cancer risk did not differ by randomized vitamin E treatment assignment (p for interaction = 0.94) or by postmenopausal hormone use (p for interaction = 0.71). Analyses according to menopausal status suggested a nonsignificant interaction between multivitamin supplement use and menopausal status in relation to the risk of invasive breast cancer (p for interaction = 0.20). The multivariable relative risks were 1.31 (95 percent CI: 0.83, 2.05) for past users and 1.36 (95 percent CI: 0.85, 2.18) for current users among premenopausal women, and they were 0.89 (95 percent CI: 0.72, 1.09) for past users and 0.82 (95 percent CI: 0.66, 1.03) for current users among postmenopausal women ( Table 4 ).

Multivariable relative risks (RRs; values given above the bars) of breast cancer by multivitamin use and alcohol intake in the Women's Health Study, United States, 1992–2004. The reference group for all comparisons was women who were never users of multivitamins and nondrinkers of alcohol.

Separate analyses according to various hormone receptor statuses revealed a nonsignificant inverse association between status of multivitamin supplement use and risk of developing ER–PR– breast cancer; the multivariable relative risks were 0.67 (95 percent CI: 0.42, 1.06) for past users and 0.73 (95 percent CI: 0.45, 1.20) for current users ( Table 5 ). Such an association was significant for past users who took multivitamin supplements for 5 or more years (multivariable RR = 0.46, 95 percent CI: 0.22, 0.96). Past use for 5 or more years was also significantly associated with reduced risk of developing breast tumors with no lymph node metastasis (multivariable RR = 0.68, 95 percent CI: 0.49, 0.94), but no significant association was observed for tumors metastasized to lymph nodes ( Table 6 ). In addition, multivitamin use was nonsignificantly associated with a reduced risk of developing ≤2-cm breast tumors but an increased risk for >2-cm tumors. No significant associations for multivitamin supplement use and breast cancer risk were found according to histologic grading and differentiation (data not shown).


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