Our analyses of multivitamin and supplement use during chemotherapy by women enrolled in this clinical trial for high-risk breast cancer indicate that, in general, supplement use decreased during chemotherapy. However, use of vitamin B6 increased, and while the percentage of vitamin B12 users decreased slightly, more users reported vitamin B12 use at a high dosage during treatment than before diagnosis, perhaps to alleviate side effects of chemotherapy including neuropathy and anemia. Use of vitamin D also increased during treatment.
Supplement use in our study differed from previously published results. It has been reported that approximately 45–80 % of breast cancer patients in the United States use antioxidant supplements, including during treatment [19
]. In the LIBCSP, 60.5 % of breast cancer patients reported using supplements during treatment, and 38 % reported using antioxidants during chemotherapy [5
]. Of antioxidant users, 69 % used doses higher than those contained in a multivitamin. In our study of participants in a Cooperative Group clinical trial, the use of supplements was much lower at baseline (20 % used vitamin C at least once per week, 15 % used vitamin E at least once per week) and particularly lower during the course of chemotherapy (12 % used vitamin C at least once per week, 8 % used vitamin E at least once per week). This unexpected finding of low use at baseline could be due to temporal changes in awareness with growing publicity and recommendations that supplements may reduce treatment efficacy. The source populations may differ as well. Participants in both the LIBCSP and LACE studies were older on average than participants in our study (58.3 and 56.3 years versus 51.3, respectively) [5
]. Women were enrolled onto S0221 at sites throughout the country, from large metropolitan cancer centers to community oncology group programs in more rural areas, which may suggest that our sample is more representative of the general population in the U.S. Supplement use may be lower because the patients in this study had high-risk breast cancer, and may be less willing to use something with unknown effects on cancer therapy.
Despite the body of data from laboratory and preclinical studies demonstrating that supplements may interfere with chemotherapeutic efficacy, it is still unclear if use of supplements during treatment has any effect on therapeutic outcomes, as few data are available. In a prospective study of 1,038 patients with stage III colon cancer enrolled in the NCI-sponsored Cancer and Leukemia Group B, Ng and colleagues found no significant survival benefit to multivitamin use during treatment [20
]. In a review of 22 peer-reviewed studies, Greenlee et al. [19
] concluded that “findings did not support any conclusions regarding the effects of individual antioxidant supplements during conventional breast cancer treatment on toxicities, tumor response, recurrence, or survival.” Data from the Shanghai Breast Cancer Survival Study, a large cohort of breast cancer patients with 532 recurrences and 444 deaths, showed that use of vitamin E, vitamin C and multivitamins by breast cancer patients was associated with reduced risk of recurrence and survival, regardless of whether use was during chemotherapy or not [21
]. Because dietary and lifestyle factors may differ between populations, it is unclear as to whether these findings would apply to a mainly white, U.S. population.
There are some limitations in our assessment of physician recommendations. We were unable to discern whether discussions regarding multivitamin and/or supplement use were initiated by physicians or by patients. In addition, the question regarding recommendations from physicians only referred to vitamins and supplements in general, not specific supplements such as antioxidants or those that showed increases in use with chemotherapy. Furthermore, it did not distinguish use of high-dose supplements versus meeting recommended daily requirements. While a recommendation not to take any vitamins and supplements would include antioxidants, a recommendation to use vitamins and supplements may refer to other supplements than antioxidants, such as B vitamins for neuropathy. However, baseline non-users of vitamin C and E were more likely to initiate use during treatment after receiving a recommendation to use vitamins and supplements compared to those receiving no recommendation. In this study, regular vitamin C and E use, both before diagnosis and during treatment, was relatively low. When stratified by physician recommendation, sample sizes for some groups were small.
We have shown that patterns of use in this study are impacted greatly by physician recommendations. The participants in this clinical trial had “high-risk” Stage II or III breast cancer with large tumors and/or nodal involvement. Patients who enroll in a clinical trial may have more concerns about their prognosis, or may have more reliance upon or confidence in their oncologists, and this could influence the lower use than that reported in the literature. Indeed, our results show that supplement use was most likely to be stopped when patients were advised by their physicians to discontinue use. To our knowledge, this is the first study to report upon patterns of supplement use during chemotherapy in relation to recommendations from treating physicians, and the first survey of these interactions between cancer patients and their doctors. Thus, we are unable to compare our low rates of use of supplements in relation to physician recommendations to other published data on antioxidant use among breast cancer patients. A major strength of our study is the detailed assessment of multivitamin and supplement use at multiple time points, specifically before diagnosis and during breast cancer treatment. The majority of studies reporting on supplement use by cancer patients are derived from data ascertained at diagnosis, or several months following treatment, with little information on patterns during chemotherapy, which could be the most crucial time-point for effects on treatment outcomes.
In this study, a number of participants did not discuss supplement usage with their doctors. This would suggest that better patient-physician communication is needed although there are not clear empirical data upon which to base suggestions regarding habits during chemotherapy. With adequate followup time of patients enrolled in S0221, and detailed information on use of multivitamins and supplements before, during and after chemotherapy, data upon which to base those recommendations will be available for advising patients on habits during cancer therapy.