Molecular characterisation of the residual disease after neoadjuvant endocrine therapy in ER+/HER2- breast cancer uncovers biomarkers of tumour response

IF 5 2区医学 Q2 Medicine

Translational Oncology Pub Date : 2025-05-10 DOI:10.1016/j.tranon.2025.102407

Joanna I. López-Velazco , Sara Manzano , Kepa Elorriaga , Maria Otaño , Ainhara Lahuerta , Luis Álvarez , Inge Etxabe , Miren Huarte , Elvira Buch , Julia Gimenez , Vanesa Quiroga , Marta Fernandez , Sofía Aragón , Laia Paré , Aleix Prat , Isabel Álvarez-López , Maria M. Caffarel , Ander Urruticoechea

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引用次数: 0

Abstract

Background

Neoadjuvant endocrine therapy (NET) in oestrogen receptor-positive /HER2-negative breast cancer (ER+/HER2- BC) allows real-time evaluation of treatment sensitivity by monitoring tumour response and offers the opportunity of personalised therapy. However, the lack of reproducible biomarkers to assess response and long-term prognosis after NET is a significant barrier to increase its indications.

Methods

In this study we searched for clinically relevant molecular reporters of response to NET in a multicentre population of ER+/HER2- BC patients (n = 87) by using: PAM50 gene expression panel and immunohistochemical evaluation of key proteins involved in tumorigenesis.

Results

Our PAM50 analyses show that tumours changing from luminal A to normal-like subtype after NET presented better radiological and pathological tumour responses, a significant larger decrease in Ki67 at surgery, lower preoperative endocrine prognostic index score (PEPI) and lower tumour cellularity size (TCS) than those with persistent luminal A status. Patients with the highest response to NET showed the largest decrease in PAM50-derived risk of recurrence (ROR) following NET. In addition, the percentage of p53 positive cells was associated with decreased response to NET.

Conclusions

Our findings highlight the change of intrinsic subtype from luminal A to normal-like after NET as a putative biomarker characterising the patient population that obtains the highest benefit from NET. Our study also suggests that changes in PAM50-derived ROR score and p53 evaluation could also help to identify those patients. Thus, this study uncovers potential biomarkers of response to NET and prognosis, which should be validated in independent cohorts, helping to the implementation of NET in the clinical practice.

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ER+/HER2-乳腺癌新辅助内分泌治疗后残留病变的分子特征揭示了肿瘤反应的生物标志物

背景：雌激素受体阳性/HER2阴性乳腺癌（ER+/HER2- BC）的新辅助内分泌治疗（NET）可以通过监测肿瘤反应来实时评估治疗敏感性，并提供个性化治疗的机会。然而，缺乏可重复的生物标志物来评估NET后的反应和长期预后是增加其适应症的重大障碍。方法在本研究中，我们通过PAM50基因表达小组和肿瘤发生关键蛋白的免疫组织化学评估，在多中心ER+/HER2- BC患者（n = 87）中寻找临床相关的NET反应分子报告。结果我们的PAM50分析显示，NET后从腔内A转变为正常样亚型的肿瘤表现出更好的放射学和病理肿瘤反应，手术时Ki67明显下降，术前内分泌预后指数评分（PEPI）和肿瘤细胞大小（TCS）低于持续腔内A状态的肿瘤。NET反应最高的患者在NET后pam50衍生的复发风险（ROR）下降幅度最大。此外，p53阳性细胞的百分比与对NET的反应降低有关。结论我们的研究结果强调了NET后内在亚型从腔内A到正常样的变化，作为一种推定的生物标志物，表征了从NET中获得最高获益的患者群体。我们的研究还表明，pam50衍生的ROR评分和p53评估的变化也有助于识别这些患者。因此，本研究揭示了对NET的反应和预后的潜在生物标志物，这些生物标志物应该在独立的队列中进行验证，有助于NET在临床实践中的实施。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Translational Oncology ONCOLOGY-

CiteScore

8.40

自引率

2.00%

发文量

314

审稿时长

54 days

期刊介绍： Translational Oncology publishes the results of novel research investigations which bridge the laboratory and clinical settings including risk assessment, cellular and molecular characterization, prevention, detection, diagnosis and treatment of human cancers with the overall goal of improving the clinical care of oncology patients. Translational Oncology will publish laboratory studies of novel therapeutic interventions as well as clinical trials which evaluate new treatment paradigms for cancer. Peer reviewed manuscript types include Original Reports, Reviews and Editorials.