Comparison of different definitions of pathologic complete response in operable breast cancer: a pooled analysis of three prospective neoadjuvant studies of JBCRG.

Background: Neoadjuvant chemotherapy (NAC) has been accepted as one of the standard treatments for operable breast cancer. However, the term pathologic complete response (pCR) has not been consistently defined.

Methods: This study was a pooled analysis of three prospective studies of NAC conducted by JBCRG and was performed to compare the prognostic significance of different definitions of pCR. pCRs were defined as follows: QpCR, few or no remaining invasive cancer cells in the breast; CpCR, ypT0/is; CpCRbn, ypT0/isypN0; SpCR, ypT0; SpCRbn, ypT0ypN0; Grade 2b, only a few remaining cancer cells in the breast.

Results: A total of 353 patients were included. A Cox proportional hazards model revealed that hazard ratios (HRs) of each pCR were lower than 1; however, pCR was significant for disease-free survival (DFS) and overall survival (OS) only when QpCR, CpCR, and CpCRbn were used (DFS; QpCR, 0.27; CpCR, 0.39; CpCRbn, 0.42, SpCR, 0.57, SpCRbn, 0.68: OS; QpCR, 0.12; CpCR, 0.17; CpCRbn, 0.16; SpCR, 0.30, SpCRbn, 0.45). Grade 2b was also a significant prognostic variable for DFS and OS (HR: DFS, 0.19; OS, 0.15). Neither bone nor brain was the first site of recurrence in patients who achieved pCR, irrespective of the definition of pCR. Triple-negative and Her2-positive tumors tended to recur in soft tissue more frequently than the other subtypes, and luminal tumors had the lowest rate of recurrence in the brain.

Conclusions: Prognostic significance of pCR varied according to the definition of pCR, and the pattern of recurrence might be different according to pathologic response and subtype.