Reference
Nechuta Sarah, Lu Wei, Chen Zhi, et al. Vitamin supplement use during breast cancer treatment and survival: a prospective cohort study. Cancer Epidemiol Biomarkers Prev. 2011;20:262-271.
Design
Population-based prospective cohort study of women with invasive breast cancer in Shanghai, China, between 2002–2006. Women were interviewed 6 months after diagnosis regarding nutritional supplement usage, and subsequent follow-up interviews were done for a median of 4.1 years (0.5–6.2 years). Vital statistics registries were used for objective data.
Participants
4,877 women (20–75 years old) with established breast cancer diagnoses
Outcome
444 deaths (all causes) and 532 recurrences occurred in the median follow-up of 4.1 years. Approximately 36.4% never used any type of vitamin supplement after their diagnosis. Usage of singular vitamins were: vitamin C 17.5%, B vitamins 16.3%, vitamin E 7.6%, vitamin A 1.7%, and vitamin D 0.4%. In addition, about 11% reported using multivitamins.
Key Findings
Use of the antioxidants vitamin C and vitamin E during and after treatment with chemotherapy had a statistically significant impact on both mortality and risk of recurrence. Use of vitamin C, vitamin E, or multivitamins had 18% reduced mortality risk (HR=0.82; 95% CI: 0.65–1.02) and 22% reduced recurrence risk (HR=0.78; 95% CI: 0.63–0.95). As singular antioxidants, the risk reduction was more dramatic. Vitamin C use for more than 3 months conferred a 44% decrease in risk for mortality (adjusted HR, 0.56; 95% CI, 0.37–0.87) and a 38% decrease in risk for disease recurrence (adjusted HR, 0.62; 95% CI, 0.43–0.90). Vitamin E use for more than 3 months had a 48% reduced risk for both mortality (adjusted HR, 0.52; 95% CI, 0.27–1.01) and 43% for recurrence (adjusted HR, 0.57; 95% CI, 0.32–1.01). These inverse associations with antioxidant use were seen whether vitamins were taken concurrently or non-concurrently with chemotherapy. However, there was no association seen in women who underwent radiation treatment (approximately one-third of participants).
Practice Implications
The theoretical risk of interference with antioxidant compounds during treatment for cancer has been given as the reason to avoid all supplementation while receiving conventional therapies. This study should give us pause to reassess this blanket dismissal of antioxidants as contraindicated. The idea of antioxidants as interfering with treatment has undergone scrutiny for decades; unfortunately this has been more theoretical debate than scientific exploration through clinical trials. Studies such as this one, which suggest there is no detriment and quite likely a benefit to antioxidants, are desperately needed to move the discussion from the abstract to a useful data-driven conclusion.
It is possible that a deficiency in antoxidant status is detrimental; therefore repletion through low-moderate doses is beneficial.
It should be emphasized that the women polled in this study were not taking large doses of vitamins. Eighty-five percent of those taking vitamin C were taking 400 mg/day or less, and 99% of vitamin E users were taking 400 mg/day or less. This is an important consideration, and results cannot be extrapolated to higher doses. It is possible that a deficiency in antoxidant status is detrimental; therefore repletion through low-moderate doses is beneficial. It is unclear whether higher doses would have the same benefit, and future studies should address this question. To date, there has been very little study of the use of multivitamins concurrent with treatment. There is, however, data on the prevention of breast cancer through multivitamin use.
In an abstract presentation at the San Antonio Breast Conference in 2010, Dr. Jamie Matta presented a case-control study involving 268 women with recently diagnosed, untreated breast cancer and 457 controls. He found a 33% reduction in risk in women taking a multivitamin and a 41% reduction for those women taking a calcium supplement.1 His research also tracked the participants' DNA repair capacity and found that women who took a multivitamin had greater capacity to repair their DNA.
Conversely, a study of 35,329 women, over a 10-year period, found a 19% increased risk of breast cancer in multivitamin users.2 The closely watched Women’s Health Initiative found no correlation to multivitamin use and breast cancer incidence in post-menopausal women.3 According to a meta-analysis reviewing publications from 1950 through July 2010 on multivitamin use and breast cancer incidence, the Swedish study is the only one showing a possible increase in breast cancer risk with multivitamin use.4 Ultimately the authors concluded, “Multivitamin use is likely not associated with a significant increased or decreased risk of breast cancer.”
Of course, multivitamin use in the primary prevention of breast cancer has little to do with whether antioxidants confer benefit during and after diagnosis, the question posed in the current abstract. While this prospective cohort study is supportive of the use of low-moderate doses of antioxidants, clinical trials that assess their use during and after treatment are needed to substantiate these findings.
Limitations
This was a prospective cohort study with many confounders possibly influencing the outcome. The users of vitamins in this study tended to higher levels of education, income, daily intake of cruciferous vegetables, and soy protein. They also tended to have lower body mass index. Lastly, they were more likely to be nonsmokers and to drink and exercise regularly. Many of these factors may influence breast cancer recurrence. This study was also done in Shangai, China, so lack of genetic variation may have influenced results.
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