Abstract:

Objective

To investigate the clinical efficacy， prognosis and safety of apatinib combined with doxorubicin （A） + cyclophosphamide （C） sequential albumin-bound paclitaxel （T） as a neoadjuvant chemotherapy regimen in patients with triple negative breast cancer （TNBC）.

Methods

A retrospective analysis was conducted in 70 TNBC patients treated in Cangzhou Central Hospital from July 2016 to January 2020. Patients were divided into two groups based on their treatment regimens：34 patients in the control group received preoperative AC-T chemotherapy alone， while 36 patients in the observation group received AC-T chemotherapy combined with apatinib （antiangiogenic agent）. Adverse events during chemotherapy were recorded. Blood samples were collected before and after chemotherapy to measure vascular endothelial growth factor （VEGF）， thymidine kinase 1 （TK1）， and carcinoembryonic antigen （CEA） levels. Objective response rate （ORR）， pathological complete response （pCR） rate， and surgical approaches were recorded. Intergroup comparisons of pCR， ORR， and breast-conserving surgery rate were analyzed using chi-square test. Logistic regression （univariate and multivariate） was employed to identify independent predictors of pCR. Differences in serum biomarker levels between groups were compared using t test，while adverse events were analyzed by ranksum test. Cox proportional hazards regression （univariate and multivariate） was performed to identify independent prognostic factors of DFS and OS.

Results

The observation group had significantly higher pCR and breast-conserving surgery rates compared with the control group （50.0% vs 23.5%， χ²=5.717，P=0.017；44.4% vs 20.6%，χ²=4.511，P=0.034）. Tumor size， neoadjuvant chemotherapy regimen， and pre-treatment Ki-67 levels were identified as independent predictors of pCR （OR=0.85，95%CI：0.77-0.95，P=0.003；OR=11.00，95%CI：2.37-51.12， P=0.002；OR=0.04，95%CI：0-0.44，P=0.008）. The VEGF and CEA levels after neoadjuvant chemotherapy were significantly higher in the observation group than those in the control group（279.08±29.03 vs 143.15±15.73，t=24.160，P＜0.001； 2.20±0.22 vs 1.78±0.23， t=7.840，P＜0.001）. No serious adverse reactions of grade Ⅲor above were observed in either group. The incidences of recorded adverse events， including nausea/vomiting， diarrhea， leukopenia， and proteinuria， showed no statistically significant differences between the two groups （Z=-0.463， -0.202， -0.547， -0.814； P=0.643， 0.840， 0.584， 0.416）.Patients in the observation group had a significantly higher breast-conserving surgery rate compared with the control group （44.4% vs 20.6%， χ²=4.511，P=0.034）. Apatinib combined with AC-T， postmenopausal status and early stage breast cancer were protective factors of DFS （HR=0.10， 95%CI：0.02-0.51， P=0.006； HR=0.12，95%CI：0.03-0.47， P=0.002； HR=8.87，95%CI：1.87-43.77， P=0.007）.

Conclusion

The regimen of apatinib combined with AC-T for neoadjuvant chemotherapy demonstrated favorable clinical efficacy，promising prognosis and controllable safety in TNBC patients.

Key words: Breast neoplasms, Apatinib, Chemotherapy, Prognosis