In 1896, Sir George Beatson reported that removal of the ovaries from three young women with locally advanced breast cancer resulted in substantial tumor shrinkage.¹ Beatson’s report set the stage for what is arguably the anticancer treatment with the most impact in regards to lives saved: endocrine therapy (ET) for breast cancer.² Nonetheless, ET is far from 100% effective, which raises the question, Why doesn’t ET work for all patients? McGuire and colleagues³ first reported that estrogen receptor (ER) is a very potent predictive factor for ET, and subsequent studies have demonstrated that ER-negative cancers are completely refractory to ET.² Since then, investigators have focused principally on identifying acquired somatic tumor alterations in ER-positive cancers that might confer resistance to ET, including upregulation of alternative pathways such as human epidermal growth factor 2 (HER2)⁴ or the appearance of mutations in ESR1 (the gene that encodes for ER⁵) or in PIK3CA.⁶

中文翻译：

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乳腺癌的药物基因组学和内分泌治疗。

1896年，乔治·比阿特森爵士（Sir George Beatson）报道说，从三名患有局部晚期乳腺癌的年轻女性中切除卵巢导致肿瘤实质缩小。¹ Beatson的报告为可以挽救生命的最有效的抗癌治疗奠定了基础：乳腺癌的内分泌治疗（ET）。²然而，ET远非100％有效，这引发了一个问题：为什么ET不能对所有患者有效？McGuire及其同事[ ^3]首先报道了雌激素受体（ER）是ET的非常有效的预测因子，随后的研究表明ER阴性的癌症对ET完全不敏感。^2个从那以后，研究人员主要致力于确定可能对ET产生抗药性的ER阳性癌症中获得性体细胞肿瘤的改变，包括上调人类人类表皮生长因子2（HER2）⁴或ESR1（编码ER ^5的基因或PIK3CA。⁶