Exp Ther Med. 2013 Nov;6(5):1089-1095.

Treatment outcome in patients with stage III breast cancer treated with neoadjuvant chemotherapy.

Takahashi R, Toh U, Iwakuma N, Mishima M, Fujii T, Takenaka M, Koura K, Seki N, Kawahara A, Kage M, Ogo E, Shirouzu K.

Department of Surgery, Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan.

 

Abstract

Despite the good responses of patients (pts) with stage III breast cancer to neoadjuvant chemotherapy (NAC), most eventually relapse and have a poor prognosis. We investigated the prognostic indicators in pts with stage III breast cancer treated with NAC, using epirubicin and/or docetaxel. A total of 22 women with stage III breast cancer underwent NAC between January 2005 and May 2011. The regimens of NAC comprised ED (epirubicin 60 mg/m2 and docetaxel 60 mg/m2) in 10 cases, FEC (fluorouracil 500 mg/m2, epirubicin 75-100 mg/m2 and cyclophosphamide 500 mg/m2) in 10 cases and EC (epirubicin 60 mg/m2 and cyclophosphamide 600 mg/m2) in two cases. Following four cycles of each regimen, a further four cycles of D (docetaxel 70 mg/m2) were undertaken in nine cases. Subsequent to the completion of NAC and surgery, we assessed the clinicopathological results and performed prognostic analyses. Statistical analyses concerning disease-free survival (DFS) or overall survival (OS) were conducted by a Cox proportional hazard model. The median survival time was 66 months and there were 12 distant metastases and two local recurrences. Multivariate analyses showed the number of metastatic axillary lymph nodes (ALNs) [hazard ratio (HR), 1.079; P=0.023] was correlated with DFS, while the Ki-67 labeling index (HR, 1.109; P=0.042) and the number of meta-static ALNs (HR, 1.087; P=0.023) were correlated with OS. In conclusion, even if pts with stage III breast cancer show good responses to NAC using epirubicin and/or docetaxel, the majority eventually relapse and have a poor prognosis. The Ki-67 labeling index and the number of involved ALNs are suggested as prognostic indicators in stage III breast cancer.

KEYWORDS: neoadjuvant chemotherapy, prognostic indicator, stage III breast cancer, treatment outcome

PMID: 24223627

 

Supplement:

We concentrated stage III breast cancer patients who were treated with NAC using epirubicin and/or docetaxel. Each patient had locally advanced breast cancer and positive axillary lymph nodes before treatment. The intrinsic subtypes were divided into three types as fellows: six luminal/Her2-negative types, nine Her2-positive types and seven triple-negative types. The regimens of NAC mainly comprised FEC (fluorouracil, epirubicin and cyclophosphamide) and ED (epirubicin and docetaxel). Subsequent the completion of NAC and surgery, we evaluated prognostic factors associated with DFS and OS.

Clinical response to NAC was shown in 14 cases and pathological complete response was shown in 4 cases. Based on the Eastern Cooperative Oncology Group (ECOG) common toxicity criteria, grade 3 or 4 hematological toxicity was shown in 9 patients. The median survival time was 66 months and there were 14 recurrent cases (12 distant metastases and 2 local recurrences). We evaluated Ki-67 labeling index in pre-treatment biopsy specimens, due to the fact that tissue degeneration following chemotherapy often makes it difficult to identify Ki-67-positive tumor cells. Axillary nodal status was also confirmed in dissected axillary lymph nodes at the time of surgery. Although no statistical difference associated with positive nodal status was shown between three subtypes (P=0.7469, Wilcoxon test), a higher Ki-67 labeling index was shown in triple-negative types (P=0.0363, Wilcoxon test). The univariate survival analysis indicated that triple-negative types had a significantly poor prognosis, but no significant difference was shown in the multivariate analysis, due to the limited number of patients in this study.

Previous studies of NAC in locally advanced breast cancer patients have indicated that, hormone receptor status and the number of residual axillary lymph nodes was associated with a poor prognosis. Despite the limited number of stage III breast cancer patients treated with NAC, our findings suggested that a high Ki-67 labeling index in pre-treatment breast cancer tissues may be a significant prognostic factor.

Ryuji Takahashi-fig1

 

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