The clinical relevance of the host immune system in breast cancer has long been studied. Peripheral blood lymphocytes show a great potential due to the advantages of minimal invasiveness, ease of access and high homogeneity. Peripheral blood lymphocytes consists of varying subpopulations. Each subpopulation of peripheral lymphocytes plays a different part in anti-tumor immunity and thus may have different clinical relevance. However, the related studies have rarely been reported.
A total of 264 advanced breast cancer patients (ABCs) were consecutively recruited at our center between January 2015 and September 2018. All patients received the conventional regimen for advanced breast cancer. Detection of peripheral blood lymphocytes at baseline was accomplished in all 264 patients with 118 patients having ctDNA detection simultaneously. The median survival was estimated by Kaplan-Meier curve, with difference detection by log-rank test and Cox proportional hazards regression model.
The median follow-up time of the study was 13.0 months. Multivariate analysis confirmed that cytotoxic T cell (CTL) was an independent prognostic factor of PFS (P = 0.024). Pierson correlation analysis showed one and only positive correlation between tumor mutational burden (TMB) and CTL level at baseline (P = 0.015). Furthermore, baseline CTL level was only confirmed in the HER2-positive subgroup (P < 0.001) but not in the HR-positive (P = 0.333) or in the TNBC subgroup (P = 0.322). For the entire cohort, the TMB high (>75%) group had a signifiantly shorter PFS (P = 0.004) than TMB low. In the HER2-positive subgroup, the PFS of the TMB high group was shorter than for the TMB low group (P < 0.001). We further use survival data obtained from the TCGA database as a validation set to confirm our findings. As expected, 24 out of 105 HER2-positive patients with TMB high were found to have shorter PFS than TMB low (HR = 0.2, 95% CI: 0.06∼0.71, P = 0.005).
Pheripheral CTL to total lymphocyte proportion is predictive for PFS in HER2-positive ABCs but not in TNBC or HR positive. Since CTL proportion was found to positively correlate with TMB and high TMB indicates shorter PFS. Thus, the negative prognositc role of CTL was, at least, partly due to the TMB of ABCs.
Peking University Cancer Hospital-Beijing Cancer Hospital.
National Natural Science Foundation of China.
All authors have declared no conflicts of interest.