Tuesday, 24 November 2020

Peripheral cytotoxic T lymphocyte predicts first-line progression free survival in HER2-positive advanced breast cancer

 

Peripheral cytotoxic T lymphocyte predicts first-line progression free survival in HER2-positive advanced breast cancer

 

by Xiao-Ran Liu, Jian-Jun Yu, Guo-Hong Song, Li-Jun Di, Han-Fang Jiang, Ying Yan, Xu Liang, Ru-Yan Zhang, Ran Ran, Jing Wang, Han Bai, Shi-Dong Jia, Hui-Ping Li

 

The Breast: Open Access, November 11, 2020

 

Highlights

•High pCTL level predicts shorter first-line PFS in HER2-positive patients receiving anti-HER2 based regimens.

•The predictive role of pCTL level found in HER2-positive patients was not applicable in hormone-positive and triple-negative breast cancer patients.

•High level of pCTL was associated with immunosuppressive status and FGFR1 mutations in HER2-positive breast cancer patients.

Abstract 

Background

The role of peripheral blood lymphocyte (pBL) in breast cancer has long been studied. However, the predictive role of pBL in advanced breast cancer (ABC) is poorly understood.

Methods

A total of 303 patients with ABC were consecutively recruited at our center between January 2015 and September 2019. At baseline, pBL subtypes were detected in all patients with 229 blood samples available for circulating tumor DNA (ctDNA) detection. pBL was analyzed through flow cytometry. ctDNA-based gene mutations were detected using next generation sequencing. The cutoff value of pCTL was estimated by X-tile software. Progression free survival (PFS) was estimated by Kaplan-Meier curve and Cox hazard proportion regression model, with difference detection by log-rank test.

Results

Median follow-up time of the study was 21.0 months. The median age of diagnosis was 52.0 years. Among the pBL subtypes, only pCTL level was found predictive for PFS in the HER2+ patients whom received anti-HER2 therapy (13.1 vs. 5.6 months, P = 0.001). However, the predictive role of pCTL was not found in HR-positive (P = 0.716) and TNBC (P = 0.202). pCTL high associated with suppressive immune indictors including lower CD4/CD8 ratio (P = 0.004) and high level of Treg cell (P = 0.004). High occurrence of FGFR1 amplification which has been reported as immune suppressor was also found in HER2+ patients with pCTL high (22.2% vs. 4.3%, P = 0.048).

Conclusions

Higher pCTLs level associated with shorter PFS and FGFR1 mutation in HER2+ ABC patients.