Thompson CA, Rock CL, Thompson PA, et al. Vegetable intake is associated with reduced breast cancer recurrence in tamoxifen users: a secondary analysis from the Womens Healthy Eating and Living Study. Breast Cancer Res Treat, published online July 6, 2010.
Secondary analysis from the Women’s Healthy Eating and Living Study (WHEL study)
3,080 female breast cancer survivors aged 18–70, who were on average 23.5 months post-diagnosis at the time of enrollment. All participants lived in 4 western states, and the WHEL trial was conducted between the years of 1995 and 2006. Participants were diagnosed with and had completed treatment for stage I, II, or III invasive breast cancer, and at the time of enrollment were found to be without evidence of disease. The majority of participants were educated, nonsmoking, sedentary Caucasian women.
Study Parameters Assessed
The WHEL study intervention diet included a daily diet of 5 vegetables (a vegetable serving was defined as any ½-cup serving of raw or cooked vegetables or 1 cup of raw leafy vegetables excluding iceberg lettuce and white potatoes), 3 fruits, 16 oz. vegetable juice, 30 g fiber, and 20% energy from fat. The WHEL Study protocol included a baseline clinic visit to assess baseline characteristics. Dietary intakes were then assessed in 24-hour dietary recalls in 4 prescheduled telephone calls. At study entry (baseline), participants completed questionnaires regarding menopause history, use of menopausal hormone therapy, other lifestyle behaviors and cancer occurrence. Cancer outcomes were assessed from annual self-administered questionnaires, with 93% of cancers confirmed with a review of pathology reports.
In this secondary analysis, a separate subgroup analysis was performed on the effect of vegetable intake on recurrence in women taking tamoxifen compared to women not taking tamoxifen. Furthermore, the effect of cruciferous vegetable intake on recurrence rate in tamoxifen users was assessed.
WHEL participants reported mean baseline intakes of 3. 1 servings of total vegetables and 0.5 servings of cruciferous vegetables. Women in the highest tertile of vegetable intake had a significantly lower hazard of breast cancer recurrence (HR 0.69, 95% CI: 0.55–0.87) at baseline. Cruciferous vegetable intake did not produce a statistically significant decrease in the hazard of recurrence at baseline. This secondary analysis revealed that when stratified for tamoxifen use, hazard of recurrence was even lower in women in the highest tertile of vegetable intake versus non-tamoxifen users (HR 0.56, 95% CI: 0.41–0.77, P≤0.001). Furthermore, a statistically significant reduction in the hazard of recurrence was seen with cruciferous vegetable consumption in the tamoxifen users (HR 0.65, 95% CI: 0.47–0.89, P=0.006).
This secondary analysis adds to the growing number of secondary analyses of the WHEL study that elucidate benefit from vegetable intake in subpopulations of the participants. Although the WHEL study ultimately failed to find benefit from consumption of vegetables in reducing the risk of breast cancer recurrence, subsequent secondary analyses of various cohorts, such as this one, are finding benefit.
In this study, the women with the highest reported intakes of total vegetables at baseline measure had an overall lower risk of recurrence and a lower risk of developing a new primary breast cancer.
In this study, the women with the highest reported intakes of total vegetables at baseline measure had an overall lower risk of recurrence and a lower risk of developing a new primary breast cancer. This effect was most pronounced in women taking tamoxifen, and the effect was the greatest in tamoxifen users who consumed the highest quantity of cruciferous vegetables. Essentially, this study suggests that vegetable intakes above the average US intakes increase the likelihood of disease-free survival in women taking tamoxifen. This beneficial effect is amplified with cruciferous vegetable intake.
The postulated mechanisms underlying this observed relationship include the synergistic role of indole-3-carbinol (I3C) found in broccoli with tamoxifen in inducing apoptosis over tamoxifen alone. Additionally, diindolylmethane (DIM), a metabolic end-product of I3C influences the metabolism of tamoxifen away from tamoxifen N-oxide, a relatively inactive metabolite, and toward its active metabolite, 4-hydroxy tamoxifen. Other studies have demonstrated that sulfurophane, another component of broccoli, induces apoptosis in breast cancer stem cells,1 an action that theoretically would complement and strengthen the antiproliferative effects of tamoxifen.
The findings in this secondary analysis are consistent with another recent study, which demonstrated that intake of 1 serving of raw broccoli, but not cooked broccoli or vegetables overall, at least once a month reduced the risk of dying from bladder cancer by 57% (HR for disease-specific death: 0.43; 95% CI: 0.25–0.74)2. This effect was attributed to isothiocyanates, which are destroyed in the cooking of broccoli.
The data from this secondary analysis is the latest addition to several studies elucidating the benefit of vegetable intake, and cruciferous vegetables in particular, on reducing the risk of cancer recurrence. The benefit of regular consumption of cruciferous vegetables, and broccoli in particular, on reducing the risk of breast cancer recurrence in tamoxifen users are worth notice. Tamoxifen has rapidly become part of standard care for women with estrogen receptor–positive breast cancer, which represents the majority of breast cancers. Thus, the inclusion of cruciferous vegetables in the daily diet of these women is important. The amount needed for this survival benefit is reasonable for most—a baseline of 0.5 servings per day—making this an acceptable strategy.
This study was limited by the reliance upon self-reported data and thus the possibility of recall bias. Additionally, the data from this study cannot be generalized to other cohorts. Finally, as a secondary analysis, the conclusions should be verified in an independent study.
For more research involving integrative oncology, click here.
1. Li Y, Zhang T, Korkaya H, et al. Sulforaphane, a dietary component of broccoli/broccoli sprouts, inhibits breast cancer stem cells. Clin Cancer Res. 2010;16(9):2580-2590.
2. Tang L, Zirpoli GR, Guru K, et al. Intake of cruciferous vegetables modifies bladder cancer survival. Cancer Epidemiol Biomarkers Prev. 2010;19(7):1806-1811.