Prognostic significance of subtype and pathologic response in operable breast cancer; a pooled analysis of prospective neoadjuvant studies of JBCRG.

PURPOSE

In the past decade, JBCRG has conducted three studies of neoadjuvant chemotherapy which have examined sequential combination of fluorouracil, epirubicin and cyclophosphamide, and docetaxel. The present study is a pooled analysis of these studies performed to determine the prognostic significance of pathologic complete response (pCR) and predictive variables for pCR.

METHODS

A total of 353 patients were included. pCR was defined as the absence of invasive cancer or only a few remaining isolated cancer cells in the breast (quasi-pCR, QpCR).

RESULTS

Disease-free survival (DFS) and overall survival (OS) were not significantly different among studies, and patients who achieved a QpCR had significantly better prognosis (DFS, p < 0.001; OS, p = 0.002). Patients with triple-negative (TN) tumors had worse prognosis than patients with the other subtypes (DFS, p = 0.03; OS, p = 0.10). A Cox proportional hazards model showed node-positive, TN, and QpCR were the significant predictors for DFS and OS among study, age, tumor size, nuclear grade, nodal status, subtype, clinical response, and pathologic response (DFS; node-positive, HR = 2.29, p = 0.001; TN, HR = 3.39, p < 0.001; QpCR, HR = 0.27, p < 0.001: OS; node-positive, HR = 3.05, p = 0.003; TN, HR = 4.92, p < 0.001; QpCR, HR = 0.12, p < 0.001). In a logistic regression analysis, subtype and clinical response before surgery were the significant predictive variables for QpCR (luminal/Her2-positive, odds ratio (OR) = 4.15, p = 0.002; Her2-positive, OR = 6.24, p < 0.001; TN, OR = 4.24, p < 0.001; clinical response before surgery, OR = 2.41, p = 0.019).

CONCLUSIONS

This study confirmed the prognostic significance of QpCR and nodal status and the predictive and prognostic significance of subtype in neoadjuvant chemotherapy.