Older women who developed invasive breast cancer while taking multivitamin supplements with minerals had a 30% lower rate of breast cancer mortality than women who did not take supplements, according to an analysis of data from the Women's Health Initiative (WHI). The finding was published online October 7 in Breast Cancer Research and Treatment.
"Our data suggest that multivitamins with minerals [MVM] have a protective role for women with breast cancer. Ours is the largest study of multivitamin supplements in postmenopausal breast cancer survivors, so we had a lot of power to uncover these associations," lead author Sylvia Wassertheil-Smoller, MD, distinguished university professor emerita of epidemiology and population health at the Albert Einstein College of Medicine of Yeshiva University, in Bronx, New York.
However, there are questions about residual confounding, mainly focused on whether the women who were taking the supplements were generally healthier.
Also, the WHI researchers emphasize that the protective effect should not be assumed to apply to women who already have breast cancer when they start taking the vitamin supplements.
Prospective Study
Dr. Wassertheil-Smoller and colleagues conducted a prospective cohort study of 7728 women 50 to 79 years of age enrolled in the WHI who were diagnosed with incident invasive breast cancer. Subjects were followed for a mean of 7.1 years.
The main study objective was to determine the effect of MVM on breast cancer mortality in these subjects. MVM use was assessed, using pill bottles brought to the clinic, at baseline and at the visit closest to the breast cancer diagnosis.
The researchers report that 37.8% of women with incident invasive breast cancer were MVM users at baseline. For the entire cohort, breast cancer mortality was 6.7%; however, it was 30% lower in MVM users than nonusers (hazard ratio [HR], 0.70).
This positive association persisted even after adjustment for potential confounding variables, including age at breast cancer diagnosis, race/ethnicity, stage of breast cancer, estrogen-receptor and progestin-receptor status of the tumor, education, smoking status, body mass index (BMI), alcohol use, physical activity, self-reported health, and diabetes.
"It appears that taking multivitamins is safe for women with breast cancer, and may be protective. However, most were taking multivitamins with minerals before they were diagnosed with breast cancer; we do not know if starting to take multivitamins after diagnosis is of benefit or harm," Dr. Wassertheil-Smoller said.
"Perhaps the women who took the multivitamins regularly were overall healthier than those who didn't, and this general good health helped to protect them from dying from breast cancer. If so, we wouldn't know if the multivitamins made them healthier or if women who were healthy and health conscious to begin with tended to be users of multivitamins. We call that confounding. We did control for many confounders, using sophisticated statistical methods, but still there could be residual confounding," she explained.
The possibility of confounding was also raised by Jaakko Mursu, MD, from the Institute of Public Health and Clinical Nutrition at the University of Eastern Finland in Kuopio, who was approached by Medscape Medical News for comment. Dr. Mursu was not involved in the WHI study, but she was lead author on a report from the Iowa Women's Health Study that showed that multivitamin use had little impact on total mortality risk (HR, 1.06 for users vs nonusers) in a general population of older women (Arch Intern Med. 2011;171:1625-1633). However, that study did not specifically examine mortality in women with breast cancer.
Dr. Mursu noted that the WHI study was an observational study, and such studies have a few methodological challenges. "Women taking multivitamins with minerals at baseline were slightly older, more likely to be white, had a higher education and income, were less likely to be current smokers, were more likely to have a lower BMI and waist/hip ratio, were more active, had higher levels of self-reported general health, and were less likely to have a history of diabetes," she said.
Overall, "supplement users were healthier and had a healthier lifestyle. The researchers did their best to control for these issues in the statistical analyses, but despite this, they cannot exclude the possibility of residual confounding. Better survival among breast cancer patients who used supplements may be the result of better health and health behavior," said Dr. Mursu.
Dr. Wassertheil-Smoller stressed that all of the subjects in the WHI study were postmenopausal women with breast cancer. "We cannot generalize to younger premenopausal women who have invasive breast cancer," she warned.
"Nevertheless," she added, "our finding of a protective effect of multivitamins with minerals is robust, and holds no matter what subgroups of women we looked at. The bottom line is that for postmenopausal women, perhaps taking a daily multivitamin and mineral supplement may be protective if they develop breast cancer. It might boost their general health. It should be noted that these supplements generally contain about 20 or more vitamins and minerals, usually at the recommended daily allowance, so these are not megadoses, which can be harmful."
The WHI is sponsored by the National Heart, Lung, and Blood Institute of the National Institutes of Health. Dr. Wassertheil-Smoller and Dr. Mursu have disclosed no relevant financial relationships.
Breast Cancer Res Treat. Published online October 9, 2013. Abstract
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