Vici Patrizia, Crispo Anna, Giordano Antonio, Di Lauro Luigi, Sperati Francesca, Terrenato Irene, Pizzuti Laura, Sergi Domenico, Mottolese Marcella, Botti Claudio, Grimaldi Maria, Capasso Immacolata, D'Aiuto Giuseppe, Di Bonito Maurizio, Di Paola Flaviano, Maugeri-Saccà Marcello, Montella Maurizio, Barba Maddalena
Division of Medical Oncology B, Regina Elena National Cancer Institute, Rome, Italy.
J Cell Physiol. 2015 Aug;230(8):1708-12. doi: 10.1002/jcp.24891.
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.
基因组和转录组分析最近为腔面B型乳腺癌的特征描述提供了详细信息。我们探讨了人体测量学、代谢和分子决定因素对这种乳腺癌亚型多方面异质性的影响，特别关注体重指数（BMI）、治疗前空腹血糖、激素受体与人表皮生长因子受体2（HER2）表达之间的关联。从意大利两个综合癌症中心诊断为腔面B型乳腺癌的154名女性中获取了大量注释样本。对参与者的特征进行了总体描述性分析，并按HER2状态（阳性与阴性）进行了分析。在回归模型中测试了BMI（<25 vs≥25）、治疗前空腹血糖（<94mg/dl的中位数 vs.≥94）和激素受体百分比与HER2表达的关联。在单变量模型中，BMI、空腹血糖以及在较小程度上雌激素受体（ER）百分比与HER2表达呈显著负相关（OR分别为：0.32，95%CI：0.16 - 0.66；0.43，0.23 - 0.82；0.96，0.94 - 0.97）。多变量模型证实了BMI和ER对HER2表达的保护作用，与对照组相比，BMI最高类别和ER表达百分比最高类别的女性中，腔面B型HER2阳性患者的比例显著更低（OR：0.22，95%CI：0.09 - 0.53；0.95，0.93 - 0.97）。总之，在腔面B型乳腺癌中，BMI和ER表达百分比与HER2表达呈负相关。经进一步证实后，这可能有助于识别在明确的乳腺癌情况下可能最受益于针对胰岛素抵抗干预措施的患者亚组。
