乳腺癌受体阳转阴的发生机理与治疗进展

Pathogenesis and therapeutic progress of breast cancer with receptor from "positive to negative"

乳腺癌因其高度异质性,给乳腺癌精准治疗带来挑战。雌激素受体(estrogen receptor, ER)、孕激素受体(progesterone receptor, PR)和人表皮生长因子受体-2(human epidermal growth factor receptor-2, HER2)状态是乳腺癌精准诊疗的重要依据。对于复发或转移性乳腺癌患者,既往治疗主要基于原发病灶受体状态。但研究发现部分患者复发/转移灶受体表达与原发病灶不同,推测可能与肿瘤异质性和治疗后的克隆选择效应相关。相较于受体表达“阴转阳”,受体“阳转阴”的发生率更高,且受体表达的缺失可能导致对原有疗法耐药且预后不良。重新评估乳腺癌复发/转移灶受体状态对调整治疗策略和判断预后具有显著临床意义,但能否基于受体变化情况指导临床决策,在临床研究或实践层面仍存在较大争议。随着靶向药物、免疫疗法及抗体偶联药物(antibody-drug conjugates, ADC)等新型抗肿瘤药物的应用,如何优化受体“阳转阴”乳腺癌患者的治疗方案以提高疗效成为未解决的临床需求。该文旨在深入探讨乳腺癌受体“阳转阴”的机理、预后影响以及治疗现状,为这类患者的治疗提供理论支持和实践指导。

Breast cancer's high degree of heterogeneity presents a challenge for precision therapy.Molecular subtypes differing from expression of estrogen receptor(ER),progesterone receptor(PR)and human epidermal growth factor receptor-2(HER2)are essential for the proper diagnosis and therapy of breast cancer.For patients with recurrent or metastatic breast cancer,previous treatments have mainly been based on the receptor status of the primary lesion.Some studies have shown that the receptor expression of recurrence/metastasis is different from that of the primary lesion,which may be related to tumor heterogeneity and post-treatment clonal selection.Compared to the conversion of receptors from"negative to positive",the rate of receptor conversion from"positive to negative"is higher,and the loss of receptor expression may result in resistance to original therapy and worse prognosis for patients.Re-evaluation of the receptor status of breast cancer recurrence/metastasis has significant clinical significance for adjusting treatment strategies and judging prognosis,but whether clinical decision-making can be guided based on receptor changes is still controversial in clinical research or practice.With the emergence of various new anti-tumor drugs,such as targeted therapies,immune therapies,and antibody-drug conjugates(ADCs),optimizing treatment decisions and maximized benefits for"positive to negative"breast cancer patients have become significant unmet needs in clinical practice.The purpose of this article is to explore the molecular mechanism,prognostic factors and current treatment status of breast cancer with“positive to negative”,in order to provide theoretical support and practical guidance for the treatment of such patients.