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 (RPFNA), 27 were registered and 24 participated in the interventional phase. The 24 biomarker evaluable women had a median baseline BMI of 34.2 kg/m2 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 < 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.

Effect of Weight Loss with or without Exercise on Inflammatory Markers and Adipokines in Postmenopausal Women: The SHAPE-2 Trial, A Randomized Controlled Trial

“…Our results on hsCRP are in line with several previous diet or exercise weight loss studies in healthy postmenopausal women (14,27,(30)(31)(32)(33)(34). Results of exercise-only interventions in a comparable population are mixed.…”

Modulation of Breast Cancer Risk Biomarkers by High-Dose Omega-3 Fatty Acids: Phase II Pilot Study in Postmenopausal Women

“…For premenopausal women who were not regularly menstruating, follicular phase of cycle was confirmed by FSH, estradiol, and progesterone levels. For the RPFNA procedure, two sites per breast were aspirated under local anesthesia as previously described with needle tip preferentially guided to areas of increased resistance [24, 30]. One-fifth of the RPFNA material was immediately placed in 0.25 ml aliquots of phosphate buffered saline in cryovials, placed in liquid nitrogen and transferred to a −80° C freezer within 12 h until assessments for fatty acid analyses, adipocytokines (Luminex®), gene expression (RT-qPCR), and proteomics.…”

“…Fasting blood [30] was obtained at the on-study visit and at 6 months within 24 hours of scheduled drug discontinuation. Insulin, glucose, adipocytokines and fatty acid analyses were performed on fasting blood.…”

Obesity, Inflammation, and Cancer

“…This is consistent with findings that calorie restriction protects mice from colonic neoplasia and reduces COX2 expression (171). Weight loss in obese, postmenopausal women has been reported to improve serum biomarkers of breast cancer risk, including SHBG, bioavailable estradiol, insulin, C-reactive protein, adiponectin, and leptin (172). Similarly, a large mixed-weight population study found that all-cause weight loss was associated with reduced colon cancer risk (173).…”