Genomic and trascriptomic profiling has recently contributed details to the characterization of
luminal B
breast cancer. We explored the contribution of anthropometric, metabolic, and molecular determinants to the multifaceted heterogeneity of this
breast cancer subtype, with a specific focus on the association between body mass index (BMI), pre-treatment fasting
glucose,
hormone receptors, and expression of
human epidermal growth factor receptor 2 (HER2). Extensively annotated specimens were obtained from 154 women with
luminal B
breast cancer diagnosed at two Italian comprehensive
cancer centres. Participants' characteristics were descriptively analyzed overall and by HER2 status (positive vs. negative). BMI (<25 vs ≥25), pre-treatment fasting
glucose (<median value of 94 mg/dl vs. ≥94) and percentage of
hormone receptors were tested for association with HER2 expression in regression models. In univariate models, BMI, fasting
glucose and, at a lesser extent, percentage of
estrogen receptors (ER) were significantly and inversely associated with HER2 expression (OR: 0.32, 95% CI: 0.16-0.66; 0.43, 0.23-0.82; 0.96, 0.94-0.97, respectively). The multivariate models confirmed the protective role of BMI and ER on HER2 expression, with
luminal B HER2 positive patients being significantly less frequent among women within the highest category of BMI and percentage expression of ER compared with their counterparts (OR: 0.22, 95% CI: 0.09-0.53; 0.95, 0.93-0.97). In conclusions, BMI and percentage of ER representation are inversely associated with HER2 expression in
luminal B breast
cancers. Upon confirmatory findings, this might help identify patient subgroups who may best benefit from the use of interventions targeting
insulin resistance in well depicted
breast cancer scenarios.