Favorable modulation of benign breast tissue and serum risk biomarkers is associated with > 10 % weight loss in postmenopausal women

Abstract

We conducted a phase II feasibility study of a 6-month behavioral weight loss intervention in postmenopausal overweight and obese women at increased risk for breast cancer and the effects of weight loss on anthropomorphic, blood, and benign breast tissue biomarkers. 67 women were screened by random peri-areolar fine-needle aspiration, 27 were registered and 24 participated in the interventional phase. The 24 biomarker evaluable women had a median baseline BMI of 34.2 kg/m(2) and lost a median of 11 % of their initial weight. Significant tissue biomarker modulation after the 6-month intervention was noted for Ki-67 (if restricted to the 15 women with any Ki-67 at baseline, p = 0.041), adiponectin to leptin ratio (p = 0.003); and cyclin B1 (p = 0.001), phosphorylated retinoblastoma (p = 0.005), and ribosomal S6 (p = 0.004) proteins. Favorable modulation for serum markers was observed for sex hormone-binding globulin (p < 0.001), bioavailable estradiol (p < 0.001), bioavailable testosterone (p = 0.033), insulin (p = 0.018), adiponectin (p = 0.001), leptin (p < 0.001), the adiponectin to leptin ratio (p < 0.001), C-reactive protein (p = 0.002), and hepatocyte growth factor (p = 0.011). When subdivided by <10 or >10 % weight loss, change in percent total body and android (visceral) fat, physical activity, and the majority of the serum and tissue biomarkers were significantly modulated only for women with >10 % weight loss from baseline. Some factors such as serum PAI-1 and breast tissue pS2 (estrogen-inducible gene) mRNA were not significantly modulated overall but were when considering only those with >10 % weight loss. In conclusion, a median weight loss of 11 % over 6 months resulted in favorable modulation of a number of anthropomorphic, breast tissue and serum risk and mechanistic markers. Weight loss of 10 % or more should likely be the goal for breast cancer risk reduction studies in obese women.

Figure 1

Representation of effects exhibited by various serum biomarkers. The relative difference (compared to baseline) is shown dichotomized into groups of women that lost <10% weight vs those that lost >10%. For all biomarkers (except PAI-1) there was a statistically significant effect of the intervention for the entire cohort of 24 evaluable subjects. The asterisks indicate a statistically significant change over time when analyzed separately for each of the two weight loss groups. For all biomarkers the effect was observed only in the >10% weight loss group; except for the molar ratio of IGF1:IGFBP3 where an increase was also observed for <10% weight loss.

Figure 2

Change over the course of the study for immunocytochemical expression of Ki-67 in RPFNA specimens of benign breast tissue. Values represent the percent of cells (of 500 counted) that exhibit staining for Ki-67 antibody.

Figure 3

Time-dependent maintenance of weight loss following completion of the 6-month study. Weight loss is expressed as relative to the baseline weight at entry on study. Open circles represent women whose weight is within +/− 5% of baseline; solid triangles represent women whose weight is >5% of their baseline weight; and solid diamonds represent women who have achieved and maintained at least a 5% reduction of their on-study weight. Not all 24 evaluable subjects could be followed for the entire 36 months.