In a large prospective cohort study of women in Northern California diagnosed with first primary breast cancer, we observed high use and initiation of vitamin and mineral supplements in the six months following diagnosis. The most commonly used supplements were multivitamins, calcium, vitamin C, and vitamin D. Only a small percent of women discontinued using specific supplements during this time. On average, the doses used by women far exceeded the recommended intake levels by the IOM. In our models, women who initiated supplements were generally highly educated, consumed more fruits and vegetables, were more likely to have ever smoked cigarettes, and were less likely to have received chemotherapy; whereas women who discontinued were more likely to be under age 50, less likely to have higher education, and did not undergo a complete mastectomy. Continuous users were more likely be older, have higher education, and consume more fruits and vegetables. In general, supplement use was greater among women who consumed more fruits and vegetables, suggesting that supplement use is higher in the population that needs supplementation the least.
Several prior studies have reported similarly high rates of vitamin/mineral supplementation among breast cancer patients and survivors [1, 3, 4, 7, 9–12, 19, 25–28]. Studies that examined use of specific supplements describe similar prevalence of multivitamin use, but much higher use of vitamins C and E than we observed [1, 4, 26]. Since supplement use data were collected over ten years ago for these studies, differences may represent new recommendations regarding antioxidant use during chemotherapy . One study reported higher rates of overall supplement use among breast cancer survivors compared to population-based controls .
In general, we report that women in the study population were somewhat more likely to discontinue than initiate supplement use. Since the commonly discontinued supplements in this population were multivitamins and vitamins C and E, we hypothesize that this difference is explained by our prospective data collection among women while they are receiving treatment. Accordingly, a recent report of high-risk breast cancer patients participating in a clinical trial observed comparable changes in use during treatment, namely decreased use of multivitamins, vitamin C, and vitamin E, consistent use of folate, and increases in vitamins B6 and B12 . However, they did not observe similar increases in vitamin D and calcium use, likely explained by younger participant age. The findings that different measures of socioeconomic status (i.e., education and income) are associated with opposite levels of use and non-use of some of the supplements is perplexing. We think that a main take home message from these findings is that different constellations of factors are associated with use of different supplements and that it is important to consider this when interpreting dietary supplement data.
The evidence-base for use of supplements during cancer treatment is inconsistent. Women are likely increasing their use of calcium and vitamin D for bone health. Prior studies suggest that calcium and vitamin D supplementation are safe for breast cancer patients [14, 30]. In the Pathways Study population, African American women reported higher use of iron and vitamin B12 before diagnosis compared to other women, likely reflecting elevated anemia risk found in African Americans . While a single study has shown that B12 may reduce breast cancer risk in premenopausal women , and other studies have shown that iron may promote carcinogenesis [33, 34], enough data do not exist to reach a clear consensus to infer causation about the risks or benefits of these dietary supplements. Folic acid and B12 are necessary to regulate DNA methylation and prevent DNA damage, but supplementation during cancer treatment is controversial . Chemotherapeutic agents such as methotrexate and 5-fluorouracil disrupt folate channels in order to promote tumor apoptosis, and supplementation during cancer treatment has the potential to reduce cytotoxicity .
Data on the effects of antioxidant use during treatment, such as vitamin E, vitamin C, and carotenoids, are mixed. There is concern that antioxidants during chemotherapy and radiation therapy may reduce treatment effectiveness . One hypothesis is that antioxidant supplements may effectively block the otherwise effective pro-oxidant therapies and therefore reduce treatment effects . However, their effects on cancer outcomes remain unclear. Observational studies report inconsistent results on use of antioxidants and risk of recurrence and mortality in breast cancer patients [4, 6]. Use of carotenoid supplements is of concern because of large human trials showing increased risk of lung cancer in those assigned to take beta-carotene [38, 39]. Use of beta-carotene as an individual supplement was not common in this population, with less than two percent reporting use after diagnosis, but many women likely use multivitamins containing beta-carotene. A recent cohort study of breast cancer patients showed increased risk of mortality among those taking combination carotenoids  but not multivitamins . Future studies utilizing information of the timing and dosage of supplement use during treatment will help clarify whether supplement interacts with or modifies the effect of conventional cancer treatments.
This study presents methodological improvements over previous studies. While several prior studies were conducted within large established cohorts, this study specifically examined changes in behavior after diagnosis, distinguishing between supplement initiators and discontinuers from continuous and never users. Therefore, it was possible to examine changes in behavior, which may affect survival outcomes and be especially relevant in establishing evidence-based recommendations for patients. This study is one of the first to prospectively collect data on supplement use shortly after diagnosis, including time during treatment. This approach differs from many prior studies where patients were queried on their supplement use far after diagnosis. Several previous studies were also limited by crude measurements of supplement intake, which make it difficult to detect small associations with cancer outcomes that are likely confounded by lifestyle and socioeconomic factors. Here we report detailed information on dose, allowing for comprehensive assessment of use patterns among continuous users, initiators, and discontinuers.
Strengths of this study include the large population of recently diagnosed women, an abundance of information on supplement use and relevant covariates, and prospective data collection. However, there are limitations. First, the participation rate in the Pathways study was 47% of the invited sample. Thus, we cannot rule out the possibility that women who enrolled in the study were healthier and more health conscious than those who did not enroll, potentially biasing our results away from the null if participants are more likely to use dietary supplements than non-participants. Differences by age and BMI at breast cancer diagnosis were minimal when comparing the enrolled to unenrolled women, respectively: average age at diagnosis 59.6 y (range: 23.6-94.8 y) vs. 61.6 y (range: 21.0-99.8 y) and 34% obese (BMI ≥ 30 kg/m2) vs. 32%. Further, the enrolled women appear largely representative of the overall breast cancer population, with a slight shift to earlier stage disease. Unenrolled women were more likely to be African American or Asian, compared to enrolled women. Second, not all women completed the 6 month follow-up questionnaire. Compared to those who completed the 6 month follow-up questionnaire, non-completers were younger, more likely to self-report as African American, Asian or Hispanic, had less education, and were diagnosed with higher stage disease. As with the non-enrollers, if the non-completers were less health conscious than the completers, study results on supplement use could be biased away from the null. In addition, this study was restricted to a single geographic region with the median education level being college graduate, which may limit generalizability of results.
A strength of the study is the detailed assessment of supplement use. Trained interviewers assessed supplement use at baseline, whereas follow-up questionnaires were completed by participants. A prior study reported low validity of self-report for some supplements, compared with the gold standard of interviewer inspection of container labels . However, most of the error was derived from extracting single micronutrient compositions from multivitamin supplements and distinguishing multiple vitamins and single supplements. A subsequent study reported high validity and reproducibility of self-administered mailed questionnaires, compared with in-person interview, and higher self-reported intakes were linearly correlated with increasing blood concentrations . Prevalence of supplement use prior to diagnosis may be overestimated because it was assessed after diagnosis, and may not accurately represent usual intake before diagnosis.