SDF-1 expression and tumor-infiltrating lymphocytes identify clinical subtypes of triple-negative breast cancer with different responses to neoadjuvant chemotherapy and survival

Abstract

BackgroundIn this study, we investigated the prediction and prognostic value of SDF-1 for triple-negative breast cancer (TNBC) patients who underwent neoadjuvant chemotherapy (NAC) following standard radical surgery.MethodsA total of 303 TNBC patients were included in this study. The NAC regimen was weekly paclitaxel plus carboplatin (PC) for all patients. SDF-1 and CXCR4 expression were measured at baseline and surgery via enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry (IHC), respectively. Correlations between variables and treatment response were studied, and Cox proportional hazards regression analysis was implemented for prognostic evaluation.ResultsOf the 303 patients, 103 (34.0%) experienced pathological complete response (pCR) after completion of NAC. Serum SDF-1 expression before NAC was significantly correlated with the abundance of TILs. A higher pCR rate was more likely to be observed in patients with lower serum SDF-1 levels before NAC (P=0.001, OR=0.997, 95% CI: 0.996-0.999) and higher levels of TILs (P=0.005). In the multivariate survival model for nonpCR patients, serum SDF-1 expression at surgery served as an independent prognostic value for survival (high level, HR=1.980, 95% CI: 1.170-3.350, low level was used as a reference; P=0.011). Additionally, the predictive and prognostic value of serum SDF-1 expression was significant in patients with high abundance of TILs but not in patients with low abundance of TILs.ConclusionsThis study contributes to the clarification of the value of serum SDF-1 to predict pCR and survival for TNBC patients who underwent NAC. This new serum marker, together with TILs, might help identify clinical subtypes of TNBC with different treatment responses and survival and play an important role in tailoring and modifying the NAC strategy for advanced TNBCs in the future.

Predictive value of stromal tumor-infiltrating lymphocytes in patients with breast cancer treated with neoadjuvant chemotherapy: A meta-analysis

“…A high expression of stromal TILs was detected in 14.83%, 24.20%, and 33.44% of HR-positive BC cases, HER-2-positive BC cases, and TNBC cases, respectively. Compared to HR-positive BC, TNBC and HER-2positive BC have stronger immunogenicity and can induce an antitumor immune response in the body to a greater extent; Asano [18] 2018 Japan 177 tBC (HR positive, HER-2 positive, TNBC) 10% FEC-P/PH Denkert [10] 2018 Germany 3651 tBC 60% NR Dong [19] 2020 China 170 TNBC 20% TEC Floris [20] 2021 Belgium 445 TNBC 30% NR Hwang [21] 2018 Korea 248 tBC 50% NR Hong [22] 2021 China 461 tBC 10% NR Ha [23] 2021 Korea 173 HER-2 positive 20% TCHP Jimenez [24] 2022 USA 80 TNBC 20% NR Kashiwagi [25] 2022 Japan 239 tBC (HR positive, HER-2 positive, TNBC) 10% FEC-P/PH Li [26] 2020 China 282 tBC 60% TAC/EC-P/T/TH Ochi [27] 2019 Japan 209 HER-2 positive, TNBC 10% NR Pang [28] 2021 China 310 TNBC 20% NR Wang [29] 2022 China 303 TNBC 50% PC FEC-P/PH = fluorouracil epirubicin cyclophosphamide-paclitaxel/paclitaxel trastuzumab, HER-2 = human epidermal growth factor receptor 2, HR = hormone receptor, NR = not reported, TAC/EC-P/T/TH = docetaxel epirubicin cyclophosphamide/epirubicin cyclophosphamide-paclitaxel/docetaxel/docetaxel trastuzumab, tBC = total breast cancer, TCHP = docetaxel carboplatin trastuzumab pertuzumab, TEC = docetaxel epirubicin cyclophosphamide, TNBC = triple-negative breast cancer, PC = paclitaxel carboplatin. www.md-journal.com consequently, stromal TILs are highly expressed in these 2 subtypes of BC.…”