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

Objective: 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.