曲妥珠单抗＋化疗效果预测新方法

　　曲妥珠单抗＋新辅助化疗已经成为HER2阳性局部晚期乳腺癌的术前标准治疗策略，可缩小肿瘤、提高手术切缘阴性率，进一步提高病理完全缓解率，还可转化为长期生存获益。不过，仍有大约20%的HER2阳性乳腺癌患者未获病理完全缓解。因此，更好地了解这些患者的特征，可能有助于改善她们生存结局。为了筛选最有可能对新辅助治疗无效患者并为她们选择最佳治疗方案，应该对未获病理完全缓解的患者特征进行充分描述，并亟需预测新辅助治疗效果的新方法。

　　2021年7月15日，瑞士《肿瘤学前沿》在线发表复旦大学附属肿瘤医院李伦、陈铭、郑舒月、李寒露、季玮儒、修秉虬、张琪、侯剑晶、王嘉、吴炅等学者的研究报告，总结了对新辅助治疗未获病理完全缓解的HER2阳性乳腺癌患者临床和基因特征，并建立了用于预测病理完全缓解的临床和基因预测模型，以优化曲妥珠单抗＋新辅助化疗的有效性。

　　该单中心队列回顾研究对复旦大学附属肿瘤医院乳腺癌数据库的600例HER2阳性早期乳腺癌术前新辅助化疗±曲妥珠单抗患者进行回顾分析，确定未获病理完全缓解的患者临床特征，建立了病理完全缓解的临床预测模型。此外，对现有基因测序数据进行回顾，建立了病理完全缓解的基因预测模型。

　　结果发现，这些患者的病理完全缓解率为39.8%。病理完全缓解与未获病理完全缓解的患者相比，无病生存率和总生存率显著较高。

　　病理完全缓解率较高的显著相关因素包括：雌激素受体阴性和孕激素受体阴性、HER2免疫组织化学评分较高、Ki-67增殖指数评分较高、曲妥珠单抗。

　　每周紫杉醇＋卡铂的病理完全缓解率最高（46.70%），蒽环类＋紫杉类方案的病理完全缓解率最低（11.11%）。

　　对四个已发表的基因表达库数据集进行分析，建立病理完全缓解的免疫特征和10基因模型。未获病理完全缓解患者的雌激素受体和孕激素受体为阳性、免疫特征和基因模型评分较低。激素受体状态和免疫特征是病理完全缓解的独立预测因素。

　　因此，该单中心队列回顾研究结果表明，激素受体状态和10基因模型可独立预测病理完全缓解，可用于患者筛选和药物疗效优化，故有必要进一步开展多中心前瞻研究进行验证。

Front Oncol. 2021 Jul 15;11:592393.

Clinical and Genetic Predictive Models for the Prediction of Pathological Complete Response to Optimize the Effectiveness for Trastuzumab Based Chemotherapy.

Li L, Chen M, Zheng S, Li H, Chi W, Xiu B, Zhang Q, Hou J, Wang J, Wu J.

Shanghai Cancer Center, Fudan University, Shanghai, China; Shanghai Medical College, Fudan University, Shanghai, China; Collaborative Innovation Center for Cancer Medicine, Shanghai, China.

BACKGROUND: Trastuzumab shows excellent benefits for HER2+ breast cancer patients, although 20% treated remain unresponsive. We conducted a retrospective cohort study to optimize neoadjuvant chemotherapy and trastuzumab treatment in HER2+ breast cancer patients.

METHODS: Six hundred patients were analyzed to identify clinical characteristics of those not achieving a pathological complete response (pCR) to develop a clinical predictive model. Available RNA sequence data was also reviewed to develop a genetic model for pCR.

RESULTS: The pCR rate was 39.8% and pCR was associated with superior disease free survival and overall survival. ER negativity and PR negativity, higher HER2 IHC scores, higher Ki-67, and trastuzumab use were associated with improved pCR. Weekly paclitaxel and carboplatin had the highest pCR rate (46.70%) and the anthracycline+taxanes regimen had the lowest rate (11.11%). Four published GEO datasets were analyzed and a 10-gene model and immune signature for pCR were developed. Non-pCR patients were ER+PR+ and had a lower immune signature and gene model score. Hormone receptor status and immune signatures were independent predictive factors of pCR.

CONCLUSION: Hormone receptor status and a 10-gene model could predict pCR independently and may be applied for patient selection and drug effectiveness optimization.

KEYWORDS: HER2; breast cancer; immune signature; neoadjuvant chemotherapy; predictive model; trastuzumab

PMID: 34336634

PMCID: PMC8319743

DOI: 10.3389/fonc.2021.592393