title: Anthropometric, metabolic and molecular determinants of human epidermal growth factor receptor 2 expression in luminal B breast cancer.
abstract: 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.
authors.affiliation: Division of Medical Oncology B, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Vici
authors.forename: Anna
authors.initials: A
authors.lastname: Crispo
authors.forename: Antonio
authors.initials: A
authors.lastname: Giordano
authors.forename: Luigi
authors.initials: L
authors.lastname: Di Lauro
authors.forename: Francesca
authors.initials: F
authors.lastname: Sperati
authors.forename: Irene
authors.initials: I
authors.lastname: Terrenato
authors.forename: Laura
authors.initials: L
authors.lastname: Pizzuti
authors.forename: Domenico
authors.initials: D
authors.lastname: Sergi
authors.forename: Marcella
authors.initials: M
authors.lastname: Mottolese
authors.forename: Claudio
authors.initials: C
authors.lastname: Botti
authors.forename: Maria
authors.initials: M
authors.lastname: Grimaldi
authors.forename: Immacolata
authors.initials: I
authors.lastname: Capasso
authors.forename: Giuseppe
authors.initials: G
authors.lastname: D'Aiuto
authors.forename: Maurizio
authors.initials: M
authors.lastname: Di Bonito
authors.forename: Flaviano
authors.initials: F
authors.lastname: Di Paola
authors.forename: Marcello
authors.initials: M
authors.lastname: Maugeri-Saccà
authors.forename: Maurizio
authors.initials: M
authors.lastname: Montella
authors.forename: Maddalena
authors.initials: M
authors.lastname: Barba
mesh_terms: D000328:Adult; D000368:Aged; D000886:Anthropometry; D001786:Blood Glucose / Q000032:analysis; D015992:Body Mass Index; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis*; D011960:Receptors, Estrogen / Q000096:biosynthesis
chemical_list: D001786:Blood Glucose; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; C508053:ERBB2 protein, human