激素受体阳性HER2阴性乳腺癌大约占初诊患者的七成，过去往往一刀切给予内分泌治疗和化疗，但是不同患者的治疗结局相差较大，部分患者的耐药、复发和转移风险较高，迫切需要针对不同患者进行精准的分型治疗。2023年，复旦大学附属肿瘤医院邵志敏教授团队根据大规模基因组学、转录组学、蛋白质组学、代谢组学、数字化病理学回顾分析，通过相似度网络融合法（SNF）将此类乳腺癌进一步分为4种亚型：经典管腔型SNF1、免疫调节型SNF2、增殖型SNF3、受体酪氨酸激酶驱动型SNF4。
2025年1月4日，美国威立出版社《癌症通讯》在线发表复旦大学附属肿瘤医院陈力①、吴文雅①、柳光宇、余科达、吴炅、狄根红、范蕾、王中华、李俊杰✉️、邵志敏✉️、复旦大学附属中山医院梁斐等学者的FINEST研究报告，对激素受体阳性HER2阴性早期乳腺癌术前新辅助治疗患者的有效性和安全性进行了复旦分型探索。
FINEST (NCT04215003): A Clinical Trial of Breast Cancer Neo-adjuvant Therapy Based on Molecular Pathway in FUSCC Official Title: This is a Phase Ib/II, Prospective , Open-label, Single Center, Bayesian Adaptive Design, Umbrella Study Evaluating the Efficacy and Safety of Neo-adjuvant Therapy in Patients With Breast Cancer.
B组：新化疗方案治疗4个周期 C组：内分泌免疫治疗4个周期（达尔西利＋来曲唑＋阿得贝利单抗，如果患者未绝经，同时给予戈舍瑞林） D组：直接进行手术
A组SNF4与非SNF4亚型相比，对白蛋白紫杉醇＋卡铂最敏感（病理完全缓解率：21.1%比1.8%） C组SNF2与非SNF2亚型相比：对内分泌免疫治疗最敏感（MP分级4-5级病理完全缓解率：45.5%比6.3%）
Cancer Commun (Lond). 2025 Jan 4. IF: 20.1
A prospective, phase II, neoadjuvant study based on chemotherapy sensitivity in HR+/HER2- breast cancer-FINEST study.
Chen L, Wu WY, Liang F, Liu GY, Yu KD, Wu J, Di GH, Fan L, Wang ZH, Li JJ, Shao ZM.
Fudan University Shanghai Cancer Centre, Shanghai, China; Shanghai Medical College, Fudan University, Shanghai, China; Zhongshan Hospital, Fudan University, Shanghai, China.
BACKGROUND: Hormone receptor-positive (HR+)/humaal growth factor receptor 2-negative (HER2-) breast cancer, the most common breast cancer type, has variable prognosis and high recurrence risk. Neoadjuvant therapy is recommended for median-high risk HR+/HER2- patients. This phase II, single-arm, prospective study aimed to explore appropriate neoadjuvant treatment strategies for HR+/HER2- breast cancer patients.
METHODS: Eligible female patients with newly diagnosed, untreated HR+/HER2- breast cancer received 2 cycles of nab-paclitaxel and carboplatin (nabPCb). Magnetic resonance imaging (MRI) was performed to assess tumor responses, and ≥ 40% regression of the maximal tumor diameter was deemed chemo-sensitive. Chemo-sensitive patients continued nabPCb for 4 more cycles (group A). Chemo-insensitive patients were randomized to groups B, C, and D at a ratio of 1:3:1 to receive a new chemotherapy for 4 cycles or endocrine-immune-based therapy (dalpiciclib, letrozole and adebrelimab, with goserelin if patients were premenopausal) for 4 cycles or to undergo surgery. Peripheral blood and core-needle biopsy (CNB) samples were collected before treatment, followed by a next-generation sequencing (NGS) panel detection and similarity network fusion (SNF) typing through digital pathology data. The primary endpoint was the pathological complete response (pCR) rate, and the secondary endpoint was the clinical objective response rate (ORR).
RESULTS: A total of 121 patients were enrolled (67.8% with stage III disease), with 76, 9, 27, and 9 patients in groups A, B, C and D, respectively. The total pCR rate was 4.1%, and all patients who received pCR were in group A. Group C had a better ORR than Group B (81.5% vs. 66.7%). Exploratory analysis revealed that patients with the SNF4 subtype were the most sensitive to nabPCb (pCR rate of 21.1% vs. 1.8% in group A), whereas patients in group C with the SNF2 subtype were more sensitive to endocrine-immune-based therapy (Miller-Payne grade 4-5, 45.5% vs. 6.3%).
CONCLUSIONS: Converting to endocrine-immune-based therapy improved the ORR, but not the pCR rate in chemo-insensitive patients. Neoadjuvant chemotherapy and endocrine therapy are not mutually exclusive. The SNF4 subtype of HR+/HER2- breast cancer was more chemo-sensitive, whereas the SNF2 subtype might be more sensitive to immunotherapy.
KEYWORDS: HER2; HR; SNF subtype; breast cancer; neoadjuvant therapy; precision treatment
PMID: 39754712
DOI: 10.1002/cac2.12649
