文章：

乳腺癌抗雌激素治疗抵抗

Therapeutic resistance to anti-oestrogen therapy in breast cancer

原文发布日期：2023-07-27

DOI: 10.1038/s41568-023-00604-3

类型: Review Article

开放获取: 否

英文摘要：

The hormone receptor oestrogen receptor-α (ER) orchestrates physiological mammary gland development, breast carcinogenesis and the progression of breast tumours into lethal, treatment-refractory systemic disease. Selective antagonism of ER signalling has been one of the most successful therapeutic approaches in oncology, benefiting patients as both a cancer preventative measure and a cancer treatment strategy. However, resistance to anti-oestrogen therapy is a major clinical challenge. Over the past decade, we have gained an understanding of how breast cancers evolve under the pressure of anti-oestrogen therapy. This is best depicted by the case of oestrogen-independent mutations in the gene encoding ER (ESR1), which are virtually absent in primary breast cancer but highly prevalent (20–40%) in anti-oestrogen-treated metastatic disease. These and other findings highlight the ‘evolvability’ of ER+ breast cancer and the need to understand molecular processes by which this evolution occurs. Recent development and approval of next-generation ER antagonists to target ESR1-mutant breast cancer underscores the clinical importance of this evolvability and sets a new paradigm for the treatment of ER+ breast cancers.

摘要翻译： 

激素受体雌激素受体α（ER）调控着生理性乳腺发育、乳腺癌发生以及乳腺肿瘤进展为致命性、治疗难治性全身性疾病的过程。选择性拮抗ER信号通路已成为肿瘤学领域最成功的治疗策略之一，作为癌症预防措施和癌症治疗手段均使患者获益。然而，抗雌激素治疗耐药性仍是临床面临的主要挑战。过去十年间，我们逐渐认识到乳腺癌在抗雌激素治疗压力下的进化机制，其中编码ER的基因ESR1发生雌激素非依赖性突变的现象最具代表性：这类突变在原发性乳腺癌中几乎不存在，但在经抗雌激素治疗的转移性病例中检出率高达20%-40%。这些发现揭示了ER阳性乳腺癌的"进化潜力"，并强调了理解其分子演进机制的必要性。新一代ER拮抗剂针对ESR1突变型乳腺癌的研发及获批，凸显了这种进化特性的临床重要性，为ER阳性乳腺癌治疗建立了新范式。

原文链接：

Therapeutic resistance to anti-oestrogen therapy in breast cancer