Gershuni Victoria, Li Yun R, Williams Austin D, So Alycia, Steel Laura, Carrigan Elena, Tchou Julia
Department of Surgery, Perelman School of Medicine, University of Pennsylvania, 3400 Civic Center Boulevard, 10th Floor South, Philadelphia, PA, 19104, USA.
Internal Medicine Residency Program, Department of Medicine, Eisenhower Medical Center, Rancho Mirage, CA, USA.
Breast Cancer Res Treat. 2017 Jun;163(2):375-381. doi: 10.1007/s10549-017-4192-x. Epub 2017 Mar 14.
Obesity is associated with tumor promoting pathways related to insulin resistance and chronic low-grade inflammation which have been linked to various disease states, including cancer. Many studies have focused on the relationship between obesity and increased estrogen production, which contributes to the pathogenesis of estrogen receptor-positive breast cancers. The link between obesity and other breast cancer subtypes, such as triple-negative breast cancer (TNBC) and Her2/neu+ (Her2+) breast cancer, is less clear. We hypothesize that obesity may be associated with the pathogenesis of specific breast cancer subtypes resulting in a different subtype distribution than normal weight women.
A single-institution, retrospective analysis of tumor characteristics of 848 patients diagnosed with primary operable breast cancer between 2000 and 2013 was performed to evaluate the association between BMI and clinical outcome. Patients were grouped based on their BMI at time of diagnosis stratified into three subgroups: normal weight (BMI = 18-24.9), overweight (BMI = 25-29.9), and obese (BMI > 30). The distribution of breast cancer subtypes across the three BMI subgroups was compared.
Obese and overweight women were more likely to present with TNBC and normal weight women with Her2+ breast cancer (p = 0.008).
We demonstrated, for the first time, that breast cancer subtype distribution varied significantly according to BMI status. Our results suggested that obesity might activate molecular pathways other than the well-known obesity/estrogen circuit in the pathogenesis of breast cancer. Future studies are needed to understand the molecular mechanisms that drive the variation in subtype distribution across BMI subgroups.
肥胖与胰岛素抵抗和慢性低度炎症相关的肿瘤促进途径有关，这些途径已与包括癌症在内的各种疾病状态相联系。许多研究聚焦于肥胖与雌激素生成增加之间的关系，这有助于雌激素受体阳性乳腺癌的发病机制。肥胖与其他乳腺癌亚型，如三阴性乳腺癌（TNBC）和人表皮生长因子受体2阳性（Her2+）乳腺癌之间的联系尚不清楚。我们假设肥胖可能与特定乳腺癌亚型的发病机制有关，导致与正常体重女性不同的亚型分布。
对2000年至2013年间诊断为原发性可手术乳腺癌的848例患者的肿瘤特征进行单机构回顾性分析，以评估体重指数（BMI）与临床结局之间的关联。根据诊断时的BMI将患者分组，分为三个亚组：正常体重（BMI = 18 - 24.9）、超重（BMI = 25 - 29.9）和肥胖（BMI > 30）。比较了三个BMI亚组中乳腺癌亚型的分布情况。
肥胖和超重女性更易患TNBC，而正常体重女性更易患Her2+乳腺癌（p = 0.008）。
我们首次证明，乳腺癌亚型分布根据BMI状态有显著差异。我们的结果表明，肥胖可能在乳腺癌发病机制中激活了除众所周知的肥胖/雌激素途径之外的分子途径。未来需要开展研究以了解驱动BMI亚组间亚型分布差异的分子机制。
