复旦大学肿瘤研究所邵志敏教授研究了使用多基因标记，为可手术三阴性乳腺癌症患者量身定制个性化辅助治疗的可行性。相关论文于2024年10月23日发表在《英国医学杂志》上。

为了评估使用多基因标记为可手术三阴性乳腺癌症患者量身定制个性化辅助治疗的可行性，2016年1月3日至2023年7月17日，研究组在中国的7个癌症中心进行了一项随机、多中心、开放标签、3期临床试验。招募18-70岁早期三阴性乳腺癌确诊手术后的女性患者。

在使用综合特征进行风险分层后，高危患者被随机（1:1）接受强化辅助治疗，包括四个周期的多西他赛、表柔比星和环磷酰胺，然后是四个周期的吉西他滨和顺铂（A组；n=166），或接受四个周期表柔比星和环磷酰胺的标准治疗，然后是4个周期的多西他赛（B组；n=170）。低风险患者接受了与B组相同的辅助化疗（C组；n=168）。在A组与B组的意向治疗分析中，主要终点是无病生存期。次要终点包括C组和B组的无病生存率、无复发生存率、总生存率和安全性。

在504名入组患者中，498名接受了研究治疗。在45.1个月的中位随访中，A组患者的三年无病生存率为90.9%，B组患者为80.6%（风险比为0.51，95%置信区间（CI）0.28至0.95；P=0.03）。A组的三年无复发生存率为92.6%，B组为83.2%（风险比0.50，95%CI 0.25至0.98；P=0.04）。A组和B组的三年总生存率分别为98.2%和91.3%（风险比0.58，95%置信区间0.22至1.54；P=0.27）。采用相同化疗方案的C组患者的无病生存率（三年无病生存率90.1%对80.6%；风险比0.57，95%CI 0.33至0.98；P=0.04）、无复发生存率（四年无复发生存率94.5%对83.2%；0.42，0.22至0.81；P=0.007）和总生存率（五年总生存率100%对91.3%；0.14，0.03至0.61；P=0.002）明显高于B组患者。A、B和C组3-4级治疗相关不良事件的发生率分别为64%（105/163）、51%（86/169）和54%（90/166）。没有发生与治疗相关的死亡。

研究结果表明，多基因标记显示了为可手术的三阴性乳腺癌症患者量身定制辅助化疗的潜力。将吉西他滨和顺铂纳入蒽环类/紫杉烷类药物治疗的强化方案显著提高了无病生存率，且毒性可控。

附：英文原文

Title: Intensive chemotherapy versus standard chemotherapy among patients with high risk, operable, triple negative breast cancer based on integrated mRNA-lncRNA signature (BCTOP-T-A01): randomised, multicentre, phase 3 trial

Author: Min He, Yi-Zhou Jiang, Yue Gong, Lei Fan, Xi-Yu Liu, Yin Liu, Li-Chen Tang, Miao Mo, Yi-Feng Hou, Gen-Hong Di, Guang-Yu Liu, Ke-Da Yu, Jiong Wu, Xia Yan, Xiao-Hua Zeng, De-Yuan Fu, Chuan-Gui Song, Zhi-Gang Zhuang, Ke-Jin Wu, Jie Wang, Zhong-Hua Wang, Zhi-Ming Shao

Issue&Volume: 2024/10/23

Abstract:

Objective To evaluate the feasibility of using a multigene signature to tailor individualised adjuvant therapy for patients with operable triple negative breast cancer.

Design Randomised, multicentre, open label, phase 3 trial.

Setting 7 cancer centres in China between 3 January 2016 and 17 July 2023.

Participants Female patients aged 18-70 years with early triple negative breast cancer after definitive surgery.

Interventions After risk stratification using the integrated signature, patients at high risk were randomised (1:1) to receive an intensive adjuvant treatment comprising four cycles of docetaxel, epirubicin, and cyclophosphamide followed by four cycles of gemcitabine and cisplatin (arm A; n=166) or a standard treatment of four cycles of epirubicin and cyclophosphamide followed by four cycles of docetaxel (arm B; n=170). Patients at low risk received the same adjuvant chemotherapy as arm B (arm C; n=168).

Main outcome measures The primary endpoint was disease-free survival in the intention-to-treat analysis for arm A versus arm B. Secondary endpoints included disease-free survival for arm C versus arm B, recurrence-free survival, overall survival, and safety.

Results Among the 504 enrolled patients, 498 received study treatment. At a median follow-up of 45.1 months, the three year disease-free survival rate was 90.9% for patients in arm A and 80.6% for patients in arm B (hazard ratio 0.51, 95% confidence interval (CI) 0.28 to 0.95; P=0.03). The three year recurrence-free survival rate was 92.6% in arm A and 83.2% in arm B (hazard ratio 0.50, 95% CI 0.25 to 0.98; P=0.04). The three year overall survival rate was 98.2% in arm A and 91.3% in arm B (hazard ratio 0.58, 95% CI 0.22 to 1.54; P=0.27). The rates of disease-free survival (three year disease-free survival 90.1% v 80.6%; hazard ratio 0.57, 95% CI 0.33 to 0.98; P=0.04), recurrence-free survival (three year recurrence-free survival 94.5% v 83.2%; 0.42, 0.22 to 0.81; P=0.007), and overall survival (three year overall survival 100% v 91.3%; 0.14, 0.03 to 0.61; P=0.002) were significantly higher in patients in arm C than in those in arm B with the same chemotherapy regimen. The incidence of grade 3-4 treatment related adverse events were 64% (105/163), 51% (86/169), and 54% (90/166) for arms A, B, and C, respectively. No treatment related deaths occurred.

Conclusions The multigene signature showed potential for tailoring adjuvant chemotherapy for patients with operable triple negative breast cancer. Intensive regimens incorporating gemcitabine and cisplatin into anthracycline/taxane based therapy significantly improved disease-free survival with manageable toxicity.

DOI: 10.1136/bmj-2024-079603

Source: https://www.bmj.com/content/387/bmj-2024-079603