Tumor-Infiltrating Lymphocytes and Survival Outcomes in Early ERBB2-Positive Breast Cancer: 10-Year Analysis of the ShortHER Randomized Clinical Trial.

Background

To evaluate the association of tumor-infiltrating lymphocytes (TILs) with distant disease-free (DDFS) and overall survival(OS) for patients with ERBB2-positive early breast cancer.

评估肿瘤浸润淋巴细胞（TILs）与早期ERBB2阳性乳腺癌患者的无远处疾病生存（DDFS）和总生存（OS）之间的关联。

DESIGN, SETTING, AND PARTICIPANTS: The ShortHER randomized clinical trial was a multicentric trial in Italy that enrolled patients with ERBB2-positive breast cancer from December 2007 to October 2013.

设计、设置和参与者：ShortHER随机临床试验是一项在意大利进行的多中心试验，从2007年12月至2013年10月招募了ERBB2阳性乳腺癌患者。

Patients received 9 weeks or 1 year of adjuvant trastuzumab combined with chemotherapy.

患者接受了9周或1年的辅助性曲妥珠单抗联合化疗。

Tumor samples were evaluated for TILs.

肿瘤样本被评估以检测肿瘤浸润淋巴细胞(TILs)。

Herein, patients were evaluated at a median follow-up of 9 years, and data were analyzed from February 2023 to August 2024.

在本研究中，患者在中位随访9年时进行了评估，数据从2023年2月至2024年8月进行了分析。

intervention

Four cycles of anthracycline-based chemotherapy followed by 4 courses of taxanes combined with trastuzumab for 1 year (long arm) or 3 courses of taxanes combined with trastuzumab for 9 weeks followed by reduced-dose anthracycline-based chemotherapy for 3 courses (short arm).

接受4个周期的葱环类药物化疗，随后是4个周期的紫杉类药物联合曲妥珠单抗治疗1年（长臂组）或3个周期的紫杉类药物联合曲妥珠单抗治疗9周，随后是3个周期的减量葱环类药物化疗（短臂组）。

main_outcomes_and_measures

The association of TILs with DDFS and OS was assessed with Cox models.

使用Cox模型评估肿瘤浸润淋巴细胞（TILs）与无病生存期（DDFS）和总生存（OS）之间的关联。

Results

Of 1253 patients enrolled in the ShortHER trial, 866 women (median [IQR] age, 56 [48-64] years) had evaluable TILs.

在ShortHER试验中，共有1253名患者入组，其中866名女性（中位年龄[四分位数间距]，56[48-64]岁）的TILs具有可评估性。

In Cox models with relevant factors, each 5% TIL increment was associated with improved DDFS (hazard ratio[HR], 0.87; 95% CI, 0.80-0.95; P = .001) and OS (HR, 0.89; 95% CI, 0.81-0.98; P = .01).

在包含相关因素的Cox模型中，每增加5%的TILs与改善的无病生存期（危险比[HR]，0.87；95%置信区间，0.80-0.95；P = .001）和总生存期（HR，0.89；95%置信区间，0.81-0.98；P = .01）相关。

The 10-year OS rate was 91.3% for patients with TILs 20% or higher, 93.3% for patients with TILs 30% or higher, and 98.1% for patients with TILs 50% or higher, resulting higher vs lower TIL counterparts.

TILs（肿瘤浸润淋巴细胞）含量20%或以上的患者10年总生存率为91.3%，TILs含量30%或以上的患者为93.3%，TILs含量50%或以上的患者为98.1%，与TILs含量较低的患者相比，生存率更高。

Patients with TILs lower than 20% showed a better outcome with the long vs short treatment (10-year DDFS, 88.7% vs 81.0%), whereas patients with TILs 20% or higher showed the opposite (10-year DDFS, 87.1% vs 92.2%; P for interaction = .01).

TILs含量低于20%的患者在接受长期治疗与短期治疗相比，10年无病生存率更高（88.7%对比81.0%），而TILs含量20%或以上的患者则相反（10年无病生存率87.1%对比92.2%；交互作用的P值为.01）。

Similarly, patients with TILs 20% or higher had a 10-year OS rate of 89.3% in the long arm vs 93.1% in the short arm (HR, 0.36; 95% CI, 0.10-1.36); patients with TILs lower than 20% had a 10-year OS rate of 91.3% in the long arm vs 86.9% in the short arm (HR, 1.36; 95% CI, 0.82-2.23; P for interaction = .06).

同样，TILs水平20%或以上的患者在长方案组的10年总生存率为89.3%，而在短方案组为93.1%（HR, 0.36; 95% 置信区间, 0.10-1.36）；TILs水平低于20%的患者在长方案组的10年总生存率为91.3%，而在短方案组为86.9%（HR, 1.36; 95% 置信区间, 0.82-2.23；交互作用P值 = .06）。

conclusions_and_relevance

This follow-up analysis of the ShortHER randomized clinical trial is, to our knowledge, the first demonstration of an independent effect of TILs in terms of OS for patients with ERBB2-positive early breast cancer treated with adjuvant chemotherapy and anti-ERBB2 therapy.

据我们所知，这是首次通过ShortHER随机临床试验的随访分析，展示了TILs对于接受辅助化疗和抗ERBB2治疗的ERBB2阳性早期乳腺癌患者的总生存具有独立影响的证据。

Patients with TILs 20% or higher who de-escalated trastuzumab duration and chemotherapy dose were not exposed to an excess risk of distant relapse or death.

TILs水平达到20%或更高的患者，在降低曲妥珠单抗的治疗时长和化疗剂量后，并未增加远处复发或死亡的风险。

trial_registration

EudraCT: 2007-004326-25.

EudraCT: 2007-004326-25。