Among women with breast cancer who participated in the LIBCSP Follow-Up Study, 38.7% reported antioxidant supplement use during chemotherapy, 42.2% during radiation therapy, and 61.9% during tamoxifen therapy. Over half of the study participants who used antioxidants during treatment consumed doses that exceeded the DRI.
The majority of participants in our study were well-educated, non-Hispanic white, postmenopausal women with high household incomes who engaged in other health-oriented behaviors prior to diagnosis (e.g., regular physical activity, high fruit and vegetable intake, not smoking). Our results are generalizable to similar populations. Almost all participants reported prior use of one or more forms of CAM. Most women who reported antioxidant supplement use during treatment, especially those women who used high doses, also engaged in other health-oriented behaviors. Women who used high dose antioxidant supplements during treatment were much more likely to have ever used herbal products and to receive tamoxifen therapy than women who did not use antioxidant supplements.
Antioxidant supplement use appears to have been more prevalent among the Long Island breast cancer patients in our sample than among respondents to the 2000 National Health Interview Survey. In that sample 51% of women, including 62% of non-Hispanic white women, reported using vitamins or minerals anytime in the past year 31
. However, in a literature review of women with a history of breast cancer, 67% to 87% reported using vitamins and minerals 9
; those figures are similar to our observations.
We found a strong association between antioxidant supplement use and tamoxifen use. This association may reflect tamoxifen users’ strategies to manage vasomotor symptoms associated with this therapy (e.g., taking vitamin E supplements to help with hot flashes 32
). We did not ask women about their motives for dietary supplement use during treatment, but previous studies have shown that women may take supplements to counteract toxicities due to breast cancer treatment 7
To our knowledge, this study is the first to report on antioxidant use during specific phases of breast cancer treatment. A recent review found eight papers reporting on vitamin/mineral supplement use among breast cancer survivors 9
, but only one focused on the 12 months post-resection 33
. A report from the Nurses Health Study showed that 20% of breast cancer survivors used high-dose vitamins during the two years prior to the assessment (mean 3.2 years post-diagnosis) 6
. Among Canadian breast cancer patients (mean 2.4 years post-diagnosis), 51.0% reported ever using vitamins and minerals other than those in a multivitamin; to treat symptoms associated with breast cancer, 13.2% used vitamin E, 12.3% used vitamin C, and 6.0% used beta-carotene 8
. Neither study reported on use during specific breast cancer treatments.
Another strength of the study is our cumulative antioxidant index and categorization of study participants as high-dose, low-dose, or non-users of multiple forms of antioxidants. We developed this approach to exposure measurement because antioxidants are rarely taken alone and may have cumulative physiological effects. Although our categorization of antioxidant use as low-dose or high-dose was based on detailed questionnaire data, it is at best an approximation of actual intake. We were conservative in calculating the specific doses of antioxidants consumed in multivitamins; hence we may have underestimated some actual doses.
The main limitation of the study is its relatively low response rate, especially compared to the high response rate of the original LIBCSP case-control study. However, we have complete first-hand follow-up questionnaire data on 764 of the 1,414 (55.4%) women who agreed to be re-contacted for the follow-up study, including the CAM questionnaire. Our response bias analyses (data not shown) showed that women who completed the full questionnaire were of higher socioeconomic status than those who did not. Because such women are also more likely than others to use CAM 34
, our study participants may have been heavier users of antioxidants than breast cancer patients in the general population.
The follow-up survey was conducted at least five years after participants were diagnosed with a first primary breast cancer. The passage of time may have led to poor recall of supplement use before diagnosis and during treatment. Despite possible misclassification, our analyses identified strong predictors of supplement use that are consistent with those reported by other investigators 3, 35, 36
Data on the actual effects of antioxidant supplements during breast cancer treatment are limited 37
. Some studies of antioxidant supplement use during treatment of other cancer sites have suggested harm 18
. In a randomized clinical trial of patients undergoing radiation therapy for head and neck cancers, α-tocopherol supplementation (400 IU/day for 3 years, beginning at the initiation of radiation therapy) was associated with a decrease in both adverse side effects during treatment 38
and overall survival at 8 years 39
. However, patients with head and neck cancer may differ from breast cancer patients in behaviors, such as tobacco use, that may be relevant to the effects of antioxidants. The effects of antioxidant supplementation during treatment may also depend on the doses and types of supplements, intake of fruits and vegetables, tumor site and stage, type of treatment, and genetic polymorphisms in endogenous antioxidant enzymes.
Areas in which further research is needed include the physiological interactions between antioxidants and radiation therapy, chemotherapy, and hormonal therapy; whether there is a dose threshold above which an antioxidant exerts benefit or harm; and the long-term effect of antioxidants on breast cancer recurrence and survival. Prospective observational studies and clinical trials need to elucidate whether antioxidants affect treatment toxicities, treatment efficacy, and recurrence and survival. Our data suggest that many women diagnosed with breast cancer who use antioxidant supplements are also engaging in other behaviors that may affect their risk of recurrence, and these behaviors should be accounted for in studies of antioxidant supplements during treatment. Results of these studies will shed light on whether or not patients can use antioxidant supplements to enhance the effects of conventional treatment or alleviate its side effects without adversely affecting their prospects for survival.
In summary, we observed that a majority of breast cancer patients in Long Island, many of whom were of high socioeconomic status, used antioxidants during treatment. We believe that oncologists should discuss supplement use and dosing with their patients. More specifically, oncologists can inform patients that antioxidant supplements may dampen the effects of chemotherapy and radiation therapy but that clear evidence of benefit or harm is not yet available 9, 18, 37