Circulating blood biomarkers correlated with the prognosis of advanced triple negative breast cancer

Abstract

Background: Immune checkpoint inhibitors (ICIs) can improve survivals of metastatic triple negative breast cancer (mTNBC); however, we still seek circulating blood biomarkers to predict the efficacy of ICIs.

Materials and methods: In this study, we analyzed the data of ICIs treated mTNBC collected in Anhui Medical University affiliated hospitals from 2018 to 2023. The counts of lymphocytes, monocytes, platelets, and ratio indexes (NLR, MLR, PLR) in peripheral blood were investigated via the Kaplan-Meier curves and the Cox proportional-hazards model.

Results: The total of 50 mTNBC patients were treated with ICIs. High level of peripheral lymphocytes and low level of NLR and MLR at baseline and post the first cycle of ICIs play the predictable role of immunotherapies. Lymphocytes counts (HR = 0.280; 95% CI: 0.095-0.823; p = 0.021) and NLR (HR = 1.150; 95% CI: 1.052-1.257; p = 0.002) are significantly correlated with overall survival. High NLR also increases the risk of disease progression (HR = 2.189; 95% CI:1.085-4.414; p = 0.029). When NLR at baseline ≥ 2.75, the hazard of death (HR = 2.575; 95% CI:1.217-5.447; p = 0.013) and disease progression (HR = 2.189; 95% CI: 1.085-4.414; p = 0.029) significantly rise. HER-2 expression and anti-tumor therapy lines are statistically correlated with survivals.

Conclusions: Before the initiation of ICIs, enriched peripheral lymphocytes and poor neutrophils and NLR contribute to the prediction of survivals.

Keywords: Anti-PD-1; Immune checkpoint inhibitors; Immunotherapy; Peripheral blood cell count; Triple-negative breast cancer.

Fig. 1

Kaplan-Meier survival curves for OS and PFS in mTNBC treated with ICIs. OS is plotted in (A, C, E, G, I) and PFS is plotted in (B, D, F, H, J). Time is represented in days from initiation of ICIs. A and B patients are stratified by PBLC (prior to ICIs). Blue lines: PBLC (prior to ICIs) < 1.10*10⁹/L; red lines: PBLC (prior to ICIs) ≥ 1.10*10⁹/L. C and D patients are stratified by PBLC (post ICIs). Blue lines: PBLC (post ICIs) < 1.10*10⁹/L; red lines: PBLC (post ICIs) ≥ 1.10*10⁹/L. E and F patients are stratified by ANC/ALC ratio (NLR). Blue lines: NLR < 2.75; red lines: NLR ≥ 2.75. G and H patients are stratified by MLR. Blue lines: MLR < 0.294; red lines: MLR ≥ 0.294. I and J patients are stratified by PLR. Blue lines: PLR < 157.28; red lines: PLR ≥ 157.2

Fig. 2

Cox proportional hazards model for OS and PFS of TNBC treated with ICIs. OS (A, C, E, G, I) and PFS (B, D, F, H, J) were plotted by COX proportional model in mTNBC. Time is presented as days from the start of immunotherapy. A and B patients are stratified by PBLC (prior to ICIs). Blue lines: PBLC (prior to ICIs) < 1.10*10⁹/L; red lines, PBLC (prior to ICIs) ≥ 1.10*10⁹/L. C and D patients are stratified by PBLC (post ICIs). Blue lines: PBLC (post ICIs) < 1.10*10⁹/L; red lines: PBLC (post ICIs) ≥ 1.10*10⁹/L. E and F patients are stratified by NLR. Blue lines: NLR < 75; red lines: NLR ≥ 2.75. G and H patients are stratified by MLR. Blue lines: MLR < 0.294 and red lines: MLR ≥ 0.294. I and J patients are stratified by PLR. Blue lines: PLR < 157.28 and red lines: PLR ≥ 157.28