UC San Diego

Background : Converging lines of research suggest that activation of the insulin/insulin-like-growth-factor axis may impact prognosis among breast cancer survivors. Carbohydrate intake can stimulate the insulin/insulin-like -growth-factor axis by elevating blood glucose concentrations, and insulin-like-growth-factor-1 receptor (IGF-1R) activation in breast cancers triggers proliferative signaling. This dissertation examined the influence of carbohydrate intake on breast cancer recurrence and all-cause mortality among postmenopausal breast cancer survivors, and whether the odds of recurrence was modified by IGF-1R expression in the primary cancer. Methods : Secondary analysis of N=2,111 postmenopausal breast cancer survivors enrolled in a dietary intervention trial. Baseline and one-year dietary intake was assessed using 24-hour dietary recalls. One- year change in carbohydrate intake was quantified as tertiles (grams/day) and change in approximately one serving of high or low quality carbohydrate-based foods; quality considered the impact on blood glucose concentrations. Samples of primary breast cancer tissue (N=265) were stained in a nested, case-control, immunohistochemical study to test the interaction between a decreased carbohydrate intake and IGF-1R expression on odds of recurrence. Finally, the impact of carbohydrate quality (high vs. low) on outcomes was assessed among the full cohort. Results : Dietary changes began a median 24 months post-diagnosis. Over a median 7 years, there were N=247 (11.7%) recurrences. Risk of recurrence significantly increased over tertiles of change in carbohydrate intake (p=0.055). A decreased carbohydrate intake (< -26 grams/day) reduced the risk of recurrence by 30% (HR: 0.7; 95%CI:0.5-1.0). Risk reduction significantly differed (p=0.110) by IGF-1R expression in the primary breast cancer: a decreased carbohydrate intake reduced the odds of recurrence by 30% (conditional OR: 0.7;95%CI:0.2- 1.7) among participants who had IGF-1R negative cancers and 80% (conditional OR: 0.2;95%CI:0.03-0.3) among participants who had IGF-1R positive cancers. Among the full cohort, only a decreased intake of low quality carbohydrates (e.g., refined grains, sweets, starchy vegetables) was protective, and only among participants who did not decrease their intake of high quality carbohydrates (e.g., fruits, non-starchy vegetables, whole grains, dairy). Conclusions : Results support that modifications in carbohydrate intake may impact prognosis among postmenopausal breast cancer survivors via the insulin/insulin-like-growth-factor axis. Importantly, carbohydrate quality may be more important that quantity relative to prognosis