近日，法国居里研究所Etienne Brain团队分析了基于基因组分级指数（ASTER 70s）评估70岁及以上高风险乳腺癌女性患者接受辅助化疗和激素治疗与仅接受辅助激素治疗的疗效。2025年8月2日，《柳叶刀》杂志发表了这一成果。

对于70岁及以上的雌激素受体阳性HER2阴性侵袭性乳腺癌患者，激素治疗是标准的辅助治疗，而化疗的作用仍存在争议。该研究旨在根据预后基因组特征评估辅助化疗对这些老年高危肿瘤患者总生存率的影响。

这项3期、随机、优势研究在法国和比利时的84个临床机构进行，患者年龄在70岁及以上，患有雌激素受体阳性和HER2阴性的原发性乳腺癌或孤立的局部复发，均在任何全身治疗前和完全手术后。基因组等级指数（GGI）测试是在中心实验室用石蜡包埋肿瘤组织上的8个基因的逆转录酶PCR检测完成的。GGI高危肿瘤患者随机分配（1:1），接受4个周期的术后紫杉烷化疗或蒽环类化疗，每3周给予一次，随后进行激素治疗（化疗组）或单独激素治疗（无化疗组）。根据G8筛查工具评分对老年虚弱、淋巴结状态和中心进行随机分层。主要终点是总生存期。

2012年4月12日至2016年4月14日，共筛查GGI患者1969例，其中GGI高危肿瘤1089例，随机分为化疗组（n=541）和非化疗组（n=548）。中位年龄75.1岁（IQR 72.5 ~ 78.7）， 437例（40%）患者存在老年性虚弱（G8评分≤14）。中位随访时间为7.8年（95% CI为7.5 ~ 7.8），化疗组4年总生存率为99.5% (95% CI为86.7% ~ 92.8)，8年总生存率为72.7%(67.8 ~ 77.7)，未化疗组4年总生存率为89.3%(86.2 ~ 91.6)，8年总生存率为68.3%(63.3 ~ 72.7)（分层log-rank p= 0.2100；风险比0.83)，4年生存率的绝对差异为1.3个百分点（95% CI -2·4至5.5），8年生存率的绝对差异为4.5% (95% CI -2·1至11.1)，统计学上无显著差异。安全性分析支持无化疗组：无化疗组548例患者中有52例（9%）发生至少1例3级或以上不良事件（包括1例与治疗无关的死亡），而化疗组541例患者中有183例（34%）发生不良事件（包括3例死亡，其中1例与治疗有关）。

研究结果表明，对于70岁及以上的GGI高危雌激素受体阳性HER2阴性乳腺癌患者，在激素治疗的基础上增加辅助化疗并没有获得生存益处，且与更多的不良事件相关，这为该老年人群在辅助激素治疗的基础上增加辅助化疗的获益-风险平衡提供了重要数据。

附：英文原文

Title: Adjuvant chemotherapy and hormonotherapy versus adjuvant hormonotherapy alone for women aged 70 years and older with high-risk breast cancer based on the genomic grade index (ASTER 70s): a randomised phase 3 trial

Author: Etienne Brain, Olivier Mir, Emmanuelle Bourbouloux, Olivier Rigal, Jean-Marc Ferrero, Sylvie Kirscher, Djelila Allouache, Véronique D’Hondt, Aude-Marie Savoye, Xavier Durando, Francois P Duhoux, Laurence Venat-Bouvet, Emmanuel Blot, Jean-Luc Canon, Florence Rollot-Trad, Hervé Bonnefoi, Telma Roque, Jérme Lemonnier, Aurélien Latouche, Julie Henriques, Magali Lacroix-Triki, Dewi Vernerey, Etienne BRAIN, Olivier MIR, Emmanuelle BOURBOULOUX, Jean-Marc FERRERO, Olivier RIGAL, Sylvie KIRSCHER, Djelila ALLOUACHE, Sophie ABADIE-LACOURTOISIE, Paul COTTU, Gilles ROMIEU, Xavier DURANDO, Aude-Marie SAVOYE, Franois DUHOUX, Laurence VENAT-BOUVET, Emmanuelle MALAURIE, Emmanuel BLOT, Sylvain LADOIRE, Catherine TERRET, Jean-Luc CANON, Véronique SERVENT, Loic MOUREY, Claudia LEFEUVRE, Elisabeth CAROLA, Lionel UWER, Véronique GIRRE, Pierre GUILLET, Marc DEBLED, Lucie MONCEAU-BAROUX, Jean-Claude DARMON, Francesco DEL PIANO, LAETITIA JOLY, Hugues BOURGEOIS, Valérie DELECROIX, Frédérique ROUSSEAU, Jean-Philippe JACQUIN, Thierry PETIT, Emmanuel BLOT, Laetitia STEFANI, Claire FALANDRY, Oana COJOCARASU, Anne MERCIER-BLAS, Carol ALLIOT, Heba DAWOOD, Eric RAYMOND, Bénédicte PETIT, Christophe TOURNIGAND, Denis HEITZ, Jean-Franois BERDAH, Marc BARON

Issue&Volume: 2025/08/02

Abstract:

Background

For women aged 70 years or older with oestrogen receptor-positive HER2-negative invasive breast cancer, hormonotherapy is a standard adjuvant treatment, while the role of chemotherapy is debated. We aimed to assess the effect of adjuvant chemotherapy on overall survival in these older patients with high-risk tumours according to a prognostic genomic signature.

Methods

This phase 3, randomised, superiority study was conducted at 84 clinical sites in France and Belgium in women aged 70 years and older with oestrogen receptor-positive and HER2-negative primary breast cancer or isolated local recurrence before any systemic treatment and after complete surgery. Genomic grade index (GGI) testing was done with a reverse-transcriptase PCR assay of eight genes on paraffin-embedded tumour tissue in a central laboratory. Patients with a GGI high-risk tumour were randomly allocated (1:1) to receive either four cycles of postoperative taxane-based or anthracycline-based chemotherapy given every 3 weeks followed by hormonotherapy (chemotherapy group) or hormonotherapy alone (no chemotherapy group). Randomisation was stratified according to the G8 screening tool score for geriatric frailty, nodal status, and centre. The primary endpoint was overall survival. This study is registered with ClinicalTrials.gov (NCT01564056) and is under active follow-up.

Findings

Between April 12, 2012 and April 14, 2016, 1969 patients were screened for GGI, of whom 1089 had a GGI high-risk tumour and were randomly allocated to the chemotherapy group (n=541) or the no chemotherapy group (n=548). Median age was 75·1 years (IQR 72·5 to 78·7) and geriatric frailty (G8 score ≤14) was identified in 437 patients (40%) patients. With a median follow-up time of 7·8 years (95% CI 7·5 to 7·8), overall survival rates were 90·5% (95% CI 87·6 to 92·8) at 4 years and 72·7% (67·8 to 77·0) at 8 years in the chemotherapy group, and 89·3% (86·2 to 91·6) at 4 years and 68·3% (63·3 to 72·7) at 8 years in the no chemotherapy group (stratified log-rank p=0·2100; hazard ratio 0·83 [95% CI 0·63 to 1·11]), yielding statistically non-significant absolute differences in survival probability of 1·3 percentage points (95% CI –2·4 to 5·0) at 4 years and 4·5% (95% CI –2·1 to 11·1) at 8 years. Safety analysis favoured the no chemotherapy group: at least one grade 3 or higher adverse event occurred in 52 (9%) of 548 patients in the no chemotherapy group (including one death not related to treatment), compared with 183 (34%) of 541 patients in the chemotherapy group (including three deaths, of which one was related to treatment).

Interpretation

The addition of adjuvant chemotherapy to hormonotherapy conferred no survival benefit in women aged 70 years and above with a GGI high-risk oestrogen receptor-positive HER2-negative breast cancer, and was associated with more adverse events, providing important data on the benefit–risk balance of adding adjuvant chemotherapy to adjuvant hormonotherapy in this older age group.

DOI: 10.1016/S0140-6736(25)00832-3

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(25)00832-3/abstract