Unit of Investigative Clinical Oncology (INCO) and Division of Medical Oncology, Piedmont Oncology Foundation/Institute for Cancer Research and Treatment, Candiolo.
Ann Oncol. 2013 Nov;24(11):2715-24. doi: 10.1093/annonc/mdt287. Epub 2013 Aug 1.
Recent data show a significant benefit from combining an anti-HER-2 agent with endocrine therapy in HER2-positive and hormone receptor (HR)-positive metastatic breast cancer. However, as the clinical outcomes achieved by these combinations do not favourably match those with chemotherapy, clinicians still perceive HER2-positive breast cancer as an homogeneous group and consider chemotherapy with anti-HER2 agents as the preferred treatment option, regardless of the HR status. Indeed, in HR-positive HER2-positive tumours, chemotherapy with anti-HER2 agents is the backbone of treatment, while endocrine therapy is commonly used in sequence when HR and HER2 are co-expressed rather than as a real alternative. Emerging biological and clinical data challenge this paradigm, suggesting that HER2-positive tumours are rather heterogeneous that HRs co-expression may account for part of this heterogeneity and, finally, that chemotherapy may represent an overtreatment in selected cases. The present review aims to summarise the biological features of HER2-positive breast cancer according to HR status, the role of the bi-directional cross-talk between HER2 and HR pathways on resistance development to anti-HER2 and endocrine therapy, and finally, the novel therapeutic strategies, including but not limited to chemotherapy, targeting these two pathways.
最近的数据表明，在 HER2 阳性和激素受体（HR）阳性转移性乳腺癌中，联合使用抗 HER2 药物和内分泌治疗具有显著益处。然而，由于这些联合治疗的临床结果并不优于化疗，临床医生仍然认为 HER2 阳性乳腺癌是一个同质的群体，并认为化疗联合抗 HER2 药物是首选的治疗方案，而不考虑 HR 状态。事实上，在 HR 阳性 HER2 阳性肿瘤中，化疗联合抗 HER2 药物是治疗的基础，而内分泌治疗通常在 HR 和 HER2 共表达时序贯使用，而不是真正的替代治疗。新兴的生物学和临床数据挑战了这一范式，表明 HER2 阳性肿瘤具有相当的异质性，HR 共表达可能是这种异质性的一部分，最后，化疗在某些情况下可能代表过度治疗。本综述旨在根据 HR 状态总结 HER2 阳性乳腺癌的生物学特征，HER2 和 HR 通路之间的双向交叉对话在抗 HER2 和内分泌治疗耐药发展中的作用，以及最后，针对这两个通路的新的治疗策略，包括但不限于化疗。
