Value of CXCL8–CXCR1/2 axis in neoadjuvant chemotherapy for triple-negative breast cancer patients: a retrospective pilot study

• Published in: Breast cancer research and treatment 2020-06, Vol.181 (3), p.561-570
• Main Authors: Wang, Ruo-Xi, Ji, Peng, Gong, Yue, Shao, Zhi-Ming, Chen, Sheng
• Format: Article
• Language: English
• Subjects: Adjuvant treatment; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biomarkers, Tumor - metabolism; Breast cancer; Cancer; Cancer patients; Cancer research; Carboplatin; Carboplatin - administration & dosage; Care and treatment; Chemotherapy; CXCR2 protein; Development and progression; Enzyme-linked immunosorbent assay; Enzymes; Female; Follow-Up Studies; Humans; Immunohistochemistry; Interleukin-8 - metabolism; Medicine; Medicine & Public Health; Middle Aged; Neoadjuvant Therapy - mortality; Oncology; Oncology, Experimental; Paclitaxel; Paclitaxel - administration & dosage; Patients; Pilot Projects; Preclinical Study; Prognosis; Receptors, Interleukin-8A - metabolism; Receptors, Interleukin-8B - metabolism; Retrospective Studies; Surgery; Survival; Survival Rate; Triple Negative Breast Neoplasms - drug therapy; Triple Negative Breast Neoplasms - metabolism; Triple Negative Breast Neoplasms - pathology; Tumors
• ISSN: 0167-6806; 1573-7217
• DOI: 10.1007/s10549-020-05660-z

Background In this study we investigate the prediction and prognostic value of CXCL8–CXCR1/2 axis for Triple-negative breast cancer (TNBC) patients underwent neoadjuvant chemotherapy (NAC) following standard radical surgery. Methods A total of 303 TNBC patients were included in this study. The NAC regimen was weekly paclitaxel plus carboplatin (PC) for all patients. Serum CXCL8 level was measured at baseline and at surgery via Enzyme-linked immunosorbent assay (ELISA). Immunohistochemistry was used to detect CXCR1 and CXCR2 expression in patients with residual tumors after NAC. Correlations between variables and treatment response were studied, and Cox proportional hazards regression analysis was implemented for prognostic evaluation. Results Of the 303 patients, 103 (34.0%) patients experienced pathological complete response (pCR) after completion of NAC. CXCL8 level was significantly upgraded after NAC in CXCR1/2+ patients and downgraded after NAC in CXCR1/2− patients. Higher pCR rate was more likely observed in patients with lower CXCL8 level at surgery ( P  = 0.004, HR 0.939, 95% CI 0.900–0.980). In the multivariate survival model, CXCR1/2 expression was of an independent prognostic value for survival (CXCR1/2+, HR 2.149, 95% CI 0.933–4.949; CXCR1/2++, HR 3.466, 95% CI 1.569–7.655, CXCR1/2− was used as a reference; P  = 0.003). Patients with higher level of CXCR1/2 expression were more likely to suffer unfavorable outcome. Conclusions This study contributes to the clarification of the value of serum CXCL8 level to predict pCR for TNBC patients, and prognostic performance of CXCR1/2 in non-pCR responders after NAC. The CXCL8–CXCR1/2 might play an important role in tailoring and modifying the NAC strategy for advanced TNBCs; however, further confirmatory studies are needed.