对于接受新辅助芳香化酶抑制剂治疗的雌激素受体阳性乳腺癌患者，突变并非内分泌抵抗的常见机制。
Mutations Are Not a Common Mechanism of Endocrine Resistance in Patients With Estrogen Receptor-Positive Breast Cancer Treated With Neoadjuvant Aromatase Inhibitor Therapy.
作者信息
Reinert Tomás, Ramalho Susana, de Vasconcelos Vivian Castro Antunes, Silva Leonardo Roberto, da Silva Ana Elisa Ribeiro, de Andrade Camila Annicchino, Kraft Maria Beatriz de Paula Leite, Coelho Guilherme Portela, Mandelli Jovana, Binotto Monique, Cabello Cesar, de Paiva Silva Geisilene Russano, Bines José, Barrios Carlos H, Ellis Matthew J, Graudenz Marcia Silveira
机构信息
Postgraduate Program in Medical Sciences, Universidade Federal Do Rio Grande Do Sul (UFRGS), Porto Alegre, Brazil.
Centro de Pesquisa da Serra Gaucha (CEPESG), Caxias Do Sul, Brazil.
出版信息
Front Oncol. 2020 Apr 3;10:342. doi: 10.3389/fonc.2020.00342. eCollection 2020.
Mutations in the gene (m) are important mechanisms of resistance to endocrine therapy in estrogen receptor-positive (ER+) metastatic breast cancer and have been studied as a potential therapeutic target, as well as a predictive and prognostic biomarker. Nonetheless, the role of m as a possible mechanism of primary endocrine resistance, as well as whether it also occurs in tumors that are resistant to ET administered in early-stage disease as (neo)adjuvant, has not been adequately studied. In this study, we evaluated the prevalence of m in tumor samples from patients with ER+ breast cancer resistant to neoadjuvant aromatase inhibitor therapy. We followed a prospective cohort of patients with ER+ HER2- stages II and III breast cancer treated with neoadjuvant endocrine therapy (NET). Tumor samples from patients with a pattern of primary endocrine resistance [defined as a Preoperative Endocrine Prognostic Index (PEPI) score of ≥4] were identified and analyzed for the presence of m. One hundred twenty-seven patients were included in the cohort, of which 100 (79%) had completed NET and underwent surgery. Among these patients, the PEPI score ranged from 0 to 3 in 70% (70/100), whereas 30% (30/100) had a PEPI score of 4 or more. Twenty-three of these patients were included in the analysis. mutations were not identified in any of the 23 patients with early-stage ER+ breast cancer resistant to NET. Growing evidence supports the notion that there are different mechanisms for primary and secondary endocrine resistance. Our study suggests that mutations do not evolve rapidly and do not represent a common mechanism of primary endocrine resistance in the neoadjuvant setting. Therefore, m should be considered a mechanism of acquired endocrine resistance in the context of advanced disease. Further research should be conducted to identify factors associated with intrinsic resistance to ET.
基因（m）的突变是雌激素受体阳性（ER+）转移性乳腺癌内分泌治疗耐药的重要机制，已被作为潜在治疗靶点以及预测和预后生物标志物进行研究。尽管如此，m作为原发性内分泌耐药的可能机制的作用，以及它是否也存在于对早期疾病作为（新）辅助治疗所给予的内分泌治疗（ET）耐药的肿瘤中，尚未得到充分研究。在本研究中，我们评估了对新辅助芳香化酶抑制剂治疗耐药的ER+乳腺癌患者肿瘤样本中m的发生率。我们对接受新辅助内分泌治疗（NET）的ER+ HER2- II期和III期乳腺癌患者进行了前瞻性队列研究。识别出具有原发性内分泌耐药模式（定义为术前内分泌预后指数（PEPI）评分≥4）的患者的肿瘤样本，并分析其中m的存在情况。该队列纳入了127例患者，其中100例（79%）完成了NET并接受了手术。在这些患者中，70%（70/100）的PEPI评分在0至3之间，而30%（30/100）的PEPI评分在4或更高。其中23例患者纳入分析。在23例对NET耐药的早期ER+乳腺癌患者中均未发现m突变。越来越多的证据支持原发性和继发性内分泌耐药存在不同机制这一观点。我们的研究表明，m突变不会迅速演变，也不代表新辅助治疗中原发性内分泌耐药的常见机制。因此，在晚期疾病背景下，m应被视为获得性内分泌耐药的一种机制。应进一步开展研究以确定与ET内在耐药相关的因素。
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