Expression of cleaved caspase-3 predicts good chemotherapy response but poor survival for patients with advanced primary triple-negative breast cancer.

Objective: To assess cleaved caspase-3 (CC3), Ki-67, and E-cadherin (E-cad) expression in relation to chemotherapy response and prognosis of patients with advanced primary triple-negative breast cancer (TNBC).

Methods: CC3 expression was detected immunohistochemically in 67 pre-chemotherapy biopsy samples. Ki67 and E-cad levels were obtained from patients' medical records.

Results: CC3-positivity (N = 32; 47.8%) was associated with a higher first-line chemotherapy overall response rate (ORR; P = 0.028) and second-line chemotherapy clinical benefit rate (CBR; P = 0.033). The Ki-67 high-risk group (N = 51; 76.1%) exhibited a reduced second-line chemotherapy CBR (P = 0.024). The E-cad negative group (N = 25; 37.3%) exhibited a lower first-line chemotherapy ORR (P = 0.044) and CBR (P<0.001), and a lower second-line chemotherapy CBR (P = 0.020). CC3, Ki-67, and E-cad were significant predictors of third-line chemotherapy ORR or CBR. Similar numbers of chemotherapy cycles were completed by the CC3-positive and -negative groups. The Ki-67 high-risk and E-cad negative groups completed fewer second-line chemotherapy cycles (P = 0.038) and fewer first-line chemotherapy cycles, respectively (P = 0.001). Kaplan-Meier analyses identified worse outcomes for the CC3-positive, Ki-67 high-risk, and E-cad negative groups than for their corresponding comparison groups (P<0.05). Multivariate Cox regression analysis identified CC3 expression and an absence of E-cad expression as independent survival factors (P<0.05).

Conclusions: Our CC3-positive group exhibited a better chemotherapy response, but a worse prognosis. The Ki-67 high-risk and E-cad negative groups exhibited both a worse chemotherapy response and worse prognosis.