BackgroundObesity is a risk factor for breast cancer in postmenopausal women and is associated with decreased survival and less favorable clinical characteristics such as greater tumor burden, higher grade, and poor prognosis, regardless of menopausal status. Despite the negative impact of obesity on clinical outcome, molecular mechanisms through which excess adiposity influences breast cancer etiology are not well-defined.MethodsAffymetrix U133 2.0 gene expression data were generated for 405 primary breast tumors using RNA isolated from laser microdissected tissues. Patients were classified as normal-weight (BMI < 25), overweight (BMI 25–29.9) or obese (BMI ≥ 30). Statistical analysis was performed by ANOVA using Partek Genomics Suite version 6.6 using a false discovery rate <0.05 to define significance.ResultsObese patients were significantly more likely to be diagnosed ≥50 years or with African American ancestry compared to lean or overweight women. Pathological characteristics including tumor stage, size or grade, lymph node status, intrinsic subtype, and breast cancer mortality did not differ significantly between groups. No significant gene expression differences were detected by BMI in a non-stratified analysis which included all subtypes or within luminal B, HER2-enriched or basal-like subtypes. Within luminal A tumors, however, 44 probes representing 42 genes from pathways such as cell cycle, p53 and mTOR signaling, DNA repair, and transcriptional misregulation were differentially expressed.ConclusionsIdentification of transcriptome differences in luminal A tumors from normal-weight compared to obese women suggests that obesity alters gene expression within ER+ tumor epithelial cells. Alterations of pathways involved in cell cycle control, tumorigenesis and metabolism may promote cellular proliferation and provide a molecular explanation for less favorable outcome of obese women with breast cancer. Targeted treatments, such as mTOR inhibitors, may allow for improved treatment and survival of obese women, especially African American women, who are more likely to be obese and suffer outcome disparities.

SummaryObjectiveMetabolic dysfunction characterized by insulin resistance (IR) is an important risk factor for type‐2 diabetes and coronary artery disease (CAD). The aim of this study was to determine if clinical lifestyle interventions differing in scope and intensity improve IR, defined by the lipoprotein IR (LPIR) score, in individuals differing in the severity of metabolic dysfunction.MethodsSubjects with diagnosed type‐2 diabetes, CAD or significant risk factors participated in one of two clinical lifestyle modification interventions: (i) intensive non‐randomized programme with a strict vegetarian diet (n = 90 participants, 90 matched controls) or (ii) moderate randomized trial following a Mediterranean‐style diet (n = 89 subjects, 58 controls). On‐treatment and intention‐to‐treat analyses assessed changes over 1 year in LPIR, lipoprotein profiles and metabolic risk factors in intervention participants and controls in both programmes.ResultsIn the on‐treatment analysis, both interventions led to weight loss: [−8.9% (95% CI, −10.3 to −7.4), intensive programme; −2.8% (95% CI, −3.8 to −1.9), moderate programme; adjusted P < 0.001] and a decrease in the LPIR score [−13.3% (95% CI, −18.2 to −8.3), intensive; −8.8% (95% CI, −12.9 to −4.7), moderate; adjusted P < 0.01] compared with respective controls. Of the six lipoprotein parameters comprising LPIR, only large very‐low‐density lipoprotein particle concentrations decreased significantly in participants compared with controls in both programmes [−26.3% (95% CI, −43.0 to −9.6), intensive; −14.2% (95% CI, −27.4 to −1.0), moderate; P < 0.05]. Intention‐to‐treat analysis confirmed and strengthened the primary results.ConclusionA stringent lifestyle modification intervention with a vegetarian diet and a moderate lifestyle modification intervention following a Mediterranean diet were both effective for improving IR defined by the LPIR score.

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<p><strong>Purpose: </strong>Breast cancer mortality rates are higher for African American women (AAW) than for any other ethnic group in the United States. Recent reports suggest that outcome disparities between AAW and European American women (EAW) are present in the ER+HER2- subtype. To improve our understanding, pathological characteristics, mortality and molecular profiles from women treated within an equal-access health care system were evaluated. <strong></strong></p><p><strong>Procedures: </strong>All AAW (n=90) and EAW (n=308) with ER+HER2- tumors were identified. Gene expression profiles were generated from primary breast tumors from 57 AAW and 181 EAW. Pathological characteristics, survival and gene expression analysis were evaluated using chi-square analysis, log-rank tests and ANOVA. </p><p><strong>Results: </strong>Tumors from AAW were significantly more likely to be PR-, Ki67+ and of higher grade. Tumor stage, size and lymph node status did not differ significantly, nor did mortality rates (P=.879). At the molecular level, genes PSPHL and CRYBB2P1 were expressed at significantly higher levels in tumor tissues as well as normal stroma and blood from AAW. Polymorphisms controlling expression of each gene were identified with minor allele frequencies differing significantly between populations but not between cases and controls within each population. <strong></strong></p><p><strong>Conclusions: </strong>Survival disparities were not detected in patients with ER+HER2- tumors treated within an equal-access health care system and molecular differences in tumors were not causal. Thus, outcome disparities in AAW with ER+HER2- tumors are largely attributable to socioeconomic factors affecting access to screening and treatment, rather than reflecting underlying biological differences. <em>Ethn Dis. </em>2016;26(3):407-416; doi:10.18865/ed.26.3.407 </p>