Study: Vegetables Reduce Risk of Breast Cancer Recurrence

reference

Thompson CA, Rock CL, Thompson PA, et al. Vegetable consumption is associated with lower breast cancer recurrence in tamoxifen users: a secondary analysis of the Womens Healthy Eating and Living Study.Breast cancer treatmentpublished online July 6, 2010.

design

Secondary analysis from the Women’s Healthy Eating and Living Study (WHEL study)

Participant

3,080 female breast cancer survivors aged 18-70 years who were an average of 23.5 months post-diagnosis at the time of enrollment. All participants lived in four western states, and the WHEL study was conducted between 1995 and 2006. Participants were diagnosed with stage I, II, or III invasive breast cancer and completed treatment with no evidence of disease. The majority of participants were educated, non-smoking, sedentary Caucasian women.

Evaluated study parameters

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 intake was then assessed during 24-hour dietary recalls in four prearranged telephone calls. At the start of the study, participants completed questionnaires about menopausal history, use of menopausal hormone therapy, other lifestyle behaviors, and occurrence of cancer. Cancer outcomes were assessed using annual self-administered questionnaires, with 93% of cancers confirmed by review of pathology reports.

In this secondary analysis, a separate subgroup analysis was performed on the effect of vegetable consumption on recurrence in women taking tamoxifen compared to women not taking tamoxifen. In addition, the effect of cruciferous vegetable intake on the recurrence rate in tamoxifen users was examined.

Key findings

WHEL participants reported an average baseline intake 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 risk of breast cancer recurrence at baseline (HR 0.69, 95% CI: 0.55-0.87). Cruciferous vegetable consumption did not result in a statistically significant decrease in the risk of recurrence at baseline. This secondary analysis found that when stratified by tamoxifen use, the risk of recurrence was even lower among women in the highest tertile of vegetable consumption compared to non-tamoxifen users (HR 0.56, 95% CI: 0.41-0.77).P≤0.001). In addition, a statistically significant reduction in the risk of recurrence with consumption of cruciferous vegetables was observed among tamoxifen users (HR 0.65, 95% CI: 0.47-0.89, P = 0.006).

Effects on practice

This secondary analysis adds to the growing number of secondary analyzes from the WHEL study that demonstrate the benefits of vegetable intake in subpopulations of participants. Although the WHEL study ultimately failed to find a benefit from eating vegetables in reducing the risk of breast cancer recurrence, subsequent secondary analyzes of different cohorts, such as this one, show a benefit.

In this study, the women with the highest reported intake of vegetables at baseline had a lower risk of recurrence overall and a lower risk of developing a new primary breast cancer.

In this study, the women with the highest reported intake of vegetables at baseline had a lower risk of recurrence overall and a lower risk of developing a new primary breast cancer. This effect was most pronounced in women taking tamoxifen and strongest in tamoxifen users who consumed the largest amount of cruciferous vegetables. Essentially, this study suggests that vegetable intakes higher than the average US intake increase the likelihood of disease-free survival in women taking tamoxifen. This beneficial effect is enhanced by consuming cruciferous vegetables.

Postulated mechanisms underlying this observed relationship include the synergistic role of indole-3-carbinol (I3C) in broccoli with tamoxifen in inducing apoptosis versus tamoxifen alone. In addition, 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 shown that sulfurophane, another component of broccoli, induces apoptosis in breast cancer stem cells.¹an effect that would theoretically complement and enhance the antiproliferative effects of tamoxifen.

The results of this secondary analysis are consistent with another recent study that showed that consuming 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 has been attributed to isothiocyanates, which are destroyed when broccoli is cooked.

The data from this secondary analysis is the latest addition to several studies demonstrating the benefits of consuming vegetables, particularly cruciferous vegetables, in reducing the risk of cancer recurrence. Of note is the benefit of regular consumption of cruciferous vegetables, particularly broccoli, in reducing the risk of breast cancer recurrence in tamoxifen users. Tamoxifen has quickly become part of the standard treatment for women with estrogen receptor-positive breast cancer, which represents the majority of breast cancers. Therefore, including cruciferous vegetables in the daily diet of these women is important. The amount required for this survival benefit is adequate for most - a baseline of 0.5 servings per day - making this an acceptable strategy.

restrictions

This study was limited by its reliance on self-reported data and therefore the potential for recall bias. Furthermore, the data from this study cannot be generalized to other cohorts. Finally, the conclusions should be tested as a secondary analysis in an independent study.

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