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Previous work found that lower BMI is associated with a pathologic complete response (pCR) following neoadjuvant chemotherapy for breast cancer. Relative dose intensity (RDI) of chemotherapy is an important marker of treatment tolerability. We hypothesized that patients with low BMI would have higher RDI than patients with high BMI, explaining the mechanism for the association between BMI and pCR. We conducted a retrospective study of women treated with neoadjuvant chemotherapy for stage I-III breast cancer at Yale New Haven Hospital-Smilow Cancer Hospital. We reviewed medical records to determine tumor characteristics, chemotherapy doses, and reasons for dose reductions or delays. The treatment RDI was calculated using published methods. Chi-squared analyses were conducted to determine the associations between RDI and BMI and between RDI and pCR. Our cohort (n = 237) had an average age of 53 years (SD 13) and mean BMI of 29.5 kg/m2 (SD 7.0). Fifty-eight patients (24%) received

Our study examined whether common variants of obesity-associated genes FTO, MC4R, BDNF, and CREB1 moderated the effects of a lifestyle intervention on weight change among breast cancer survivors. 151 breast cancer survivors with a body mass index ≥ 25 kg/m2 were randomly assigned to a 6-month weight loss intervention or usual care group. Genotyping of FTO rs9939609, MC4R rs6567160, BDNF rs11030104, CREB1 rs17203016 was performed. Linear mixed models were used including the main effects of genotype (assuming a dominant genetic model), treatment arm on weight and percent body fat changes, and genotype by treatment interaction variable. All statistical tests were evaluated against a Bonferroni-corrected alpha of 0.0125. Women in the intervention group achieved significantly greater weight loss than the usual care group (5.9% vs 0.4%, p 0.0125 for each single-nucleotide polymorphisms). Women who are genetically predisposed to obesity and recently diagnosed with breast cancer may achieve significant and clinically meaningful weight loss through healthy eating and exercise. Clinical Trial Registration: NCT02863887 (Date of Registration: August 11, 2016); NCT02110641 (Date of Registration: April 10, 2014)

Previous work found that lower BMI is associated with a pathologic complete response (pCR) following neoadjuvant chemotherapy for breast cancer. Relative dose intensity (RDI) of chemotherapy is an important marker of treatment tolerability. We hypothesized that patients with low BMI would have higher RDI than patients with high BMI, explaining the mechanism for the association between BMI and pCR.We conducted a retrospective study of women treated with neoadjuvant chemotherapy for stage I-III breast cancer at Yale New Haven Hospital-Smilow Cancer Hospital. We reviewed medical records to determine tumor characteristics, chemotherapy doses, and reasons for dose reductions or delays. The treatment RDI was calculated using published methods. Chi-squared analyses were conducted to determine the associations between RDI and BMI and between RDI and pCR.Our cohort (n = 237) had an average age of 53 years (SD 13) and mean BMI of 29.5 kg/mNearly one quarter of our cohort had RDI85%. Although RDI overall was not associated with pCR, having fewer dose delays was associated with pCR. Our results highlight a need for improved patient adherence to and tolerability of neoadjuvant chemotherapy to minimize treatment delays.

Some studies suggest that telomere shortening may be associated with increased breast cancer risk and mortality. Obesity is also associated with increased breast cancer risk and mortality. Few studies have examined changes in telomere length in overweight or obese breast cancer survivors. The purpose of our study was to examine the effect of a 6-month diet- and exercise-induced weight loss intervention versus usual care on telomere length in breast cancer survivors. 151 breast cancer survivors with body mass index (BMI) ≥ 25 kg/m2 were randomly assigned to a 6-month weight loss intervention (n = 93) or to usual care (n = 58). Fasting blood samples, height, weight, physical activity, and diet were measured at baseline and 6-months. Relative telomere length (RTL) was measured by quantitative-polymerase chain reaction (qPCR) done on buffy coat-extracted genomic DNA. Mean baseline to 6-month changes were compared between groups (intention-to-treat) using generalized estimating equations. Complete telomere data were available in 125 participants. Women were 58 ± 8 years, with BMI 33.0 ± 6.2 kg/m2 and were 2.9 ± 2.5 years from diagnosis; 90% were non-Hispanic white, and 76% had stage 0/I breast cancer. After 6 months, women randomized to weight loss had 3% telomere lengthening compared to 5% shortening in the usual care group (p = 0.12). Among women with stage 0/I, the intervention group experienced 7% telomere lengthening compared to 8% shortening in the usual care group (p = 0.01). No intervention effect was observed in women with stage II/III breast cancer. Our findings suggest a weight loss intervention in stage 0 and 1 breast cancer survivors may lead to telomere lengthening, compared to a shortening in their usual care counterparts.

PURPOSE: Obesity and weight gain are associated with comorbidities including a higher risk of tumor recurrence and cancer-related deaths among breast cancer(BC) survivors, however the underlying mechanisms linking obesity and cancer are poorly understood. Given the lack of clinically validated BC biomarkers, obesity and weight loss studies utilize serum biomarkers as intermediary outcomes of tumor recurrence. Studies have indicated microRNAs(miRNA)s are reliable biomarkers for cancer. We hypothesized that miRNA expression is correlated with obesity and weight loss amongst BC survivors. This would yield insight into the biological pathways through which this association occurs, enabling more precise development of therapeutics. PATIENTS AND METHODS: We correlated baseline body mass index(BMI) with serum miRNA expression in 121 BC survivors enrolled in the Hormones and Physical Exercise(HOPE) trial. We then analyzed expression of the 35 most abundant miRNAs from HOPE in a six-month randomized controlled weight loss trial(Lifestyle, Exercise, and Nutrition; LEAN) in 100 BC survivors. Ingenuity Pathway Analysis(IPA) software was used to identify biological pathway targets of the BMI-associated and intervention-responsive miRNAs using predictive biomarkers. RESULTS: Pearson correlations in HOPE identified eight miRNAs associated with BMI, including miR_191–5p(r=−0.22, p=0.016) and miR_122–5p(r=0.25, p=0.0048). In the LEAN validation study, levels of miR_191–5p significantly increased during the six-month intervention(p=0.082). Ingenuity Pathway Analysis identified “Estrogen-mediated S-phase entry”(HOPE p=0.003; LEAN p