Approximately 50% of HER2 positive breast cancer cases are also estrogen receptor (ER) positive. Data supports a role for close cross-talk between the ER and HER2 signaling pathways as an important contributor to the development of de novo or acquired resistance to hormone therapies. Therefore a strategy that simultaneously blocks both signaling pathways is a reasonable approach to prevent or overcome either endocrine or anti-HER2 therapy resistance. Moreover, preclinical data support the idea that PI3K inhibitors and CDK4/6 could be an attractive target that functions downstream of both ER and HER2 pathways. We conducted a literature review of the results of phase II and III studies testing targeted therapies in metastatic breast cancer with HER2-positive and hormonal-receptor-positive disease. The analyses included efficacy and toxicity data from earlier studies with a single anti-HER2 drug combined with hormonal therapy up to more recent studies testing new molecules targeting these signaling pathways. The aims of this review are to summarize current knowledge and to discuss research development including the possibility to spare chemotherapy in this subgroup of HER2-positive breast cancer patients.

中文翻译：

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激素治疗与靶向治疗相结合治疗内分泌反应性和 HER2 阳性转移性乳腺癌。


大约 50% HER2 阳性乳腺癌病例也是雌激素受体 (ER) 阳性。数据支持 ER 和 HER2 信号通路之间的密切交互作用，作为对激素疗法的从头或获得性耐药性发展的重要贡献者。因此，同时阻断两条信号通路的策略是预防或克服内分泌或抗 HER2 治疗耐药性的合理方法。此外，临床前数据支持这样的观点：PI3K 抑制剂和 CDK4/6 可能是在 ER 和 HER2 通路下游发挥作用的有吸引力的靶标。我们对测试 HER2 阳性和激素受体阳性转移性乳腺癌靶向治疗的 II 期和 III 期研究结果进行了文献综述。这些分析包括早期研究中单一抗 HER2 药物联合激素疗法的疗效和毒性数据，以及最近测试针对这些信号通路的新分子的研究。本综述的目的是总结当前知识并讨论研究进展，包括在 HER2 阳性乳腺癌患者亚组中免除化疗的可能性。