Abstract P1-06-02: The Protective Effect of a Dietary Intervention on Additional Breast Cancer Events Is Limited to Those with Higher Baseline Testosterone Concentrations
Authors: Emond JA , Patterson RE , Natarajan L , Laughlin GA , Gold EB , Pierce JP. 
Published: April 2011

Abstract
In 2007, the Women's Healthy Eating and Living (WHEL) Study reported that among breast cancer survivors, adoption of a diet high in fruits, vegetables, and fiber and low in fat did not improve breast cancer prognosis over 7.3 years of follow-up. However, in a subgroup of women who reported not having hot flashes at baseline, the intervention significantly reduced the risk of additional breast cancer events. The absence of hot flashes in postmenopausal women is believed to be a marker of higher circulating estrogen levels. Therefore, this analysis was to determine if the WHEL intervention was associated with significant changes in sex hormone concentrations, and to examine if the protective effect of the WHEL intervention was modified by baseline hormone levels. Methods: Baseline and year one concentrations of total and bioavailable estradiol, total and bioavailable testosterone, and sex hormone binding globulin (SHBG) were compared by intervention arm among 447 postmenopausal women without hot flashes. Women who experienced an additional breast cancer event in the first year of the study were excluded. In separate Cox proportional hazard models, we tested interaction terms of study arm with baseline hormone concentrations, adjusted for study site, anti-estrogen use, number of positive nodes, tumor size, oophorectomy status, and hormone replacement therapy use; age and other medical/clinical measures did not differ by arm nor were related to outcome. Results: In this sample, the intervention remained protective against additional breast cancer events (adjusted HR 0.51, 95% CI: 0.30-0.85; p=0.011). Baseline median values for hormones were: 8 pg/mL total estradiol, 4.5 pg/mL bioavailable estradiol, 27.2 ng/dL total testosterone, 11.0 ng/dL bioavailable testosterone, 60.5 nmol/L SHBG. Sex hormone concentrations at baseline and year one did not differ by study arm nor did they change over the first year in either study arm. However, a statistically significant interaction was seen between study arm and baseline testosterone. Specifically, the protective effect of the intervention increased among women with higher baseline total or bioavailable testosterone concentrations. No significant interactions were seen with estradiol or SHBG. Results were similar for women who did not undergo any oophorectomies (n=357).
Discussion: The WHEL dietary intervention did not change concentrations of sex hormones over the first year of the study in this subset. These results suggest that the intervention may have modified other risk factors correlated with baseline testosterone (e.g., biomarkers in the insulin-IGF axis). This study was limited by sample size and the post-hoc nature of the analyses. Further research is needed to clarify the role of diet and biomarkers with additional breast cancer events in breast cancer survivors.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-06-02.