Measurement of Residual Breast Cancer Burden to Predict Survival After Neoadjuvant Chemotherapy

TLDR

The study quantified residual disease after neoadjuvant chemotherapy using a continuous residual cancer burden (RCB) index that integrates primary tumor size, cellularity, and nodal metastasis measurements from 382 patients in two treatment cohorts, and used it to predict distant relapse‑free survival. RCB demonstrated that minimal residual disease (RCB‑I) confers a prognosis equivalent to pathologic complete response, while extensive residual disease (RCB‑III) predicts poor survival regardless of hormone status or adjuvant therapy, and the index reliably predicts distant relapse‑free survival across both cohorts, enabling categorization of near‑complete response and chemotherapy resistance.

Abstract

To measure residual disease after neoadjuvant chemotherapy in order to improve the prognostic information that can be obtained from evaluating pathologic response.Pathologic slides and reports were reviewed from 382 patients in two different treatment cohorts: sequential paclitaxel (T) then fluorouracil, doxorubicin, and cyclophosphamide (FAC) in 241 patients; and a single regimen of FAC in 141 patients. Residual cancer burden (RCB) was calculated as a continuous index combining pathologic measurements of primary tumor (size and cellularity) and nodal metastases (number and size) for prediction of distant relapse-free survival (DRFS) in multivariate Cox regression analyses.RCB was independently prognostic in a multivariate model that included age, pretreatment clinical stage, hormone receptor status, hormone therapy, and pathologic response (pathologic complete response [pCR] v residual disease [RD]; hazard ratio = 2.50; 95% CI 1.70 to 3.69; P < .001). Minimal RD (RCB-I) in 17% of patients carried the same prognosis as pCR (RCB-0). Extensive RD (RCB-III) in 13% of patients was associated with poor prognosis, regardless of hormone receptor status, adjuvant hormone therapy, or pathologic American Joint Committee on Cancer stage of residual disease. The generalizability of RCB for prognosis of distant relapse was confirmed in the FAC-treated validation cohort.RCB determined from routine pathologic materials represented the distribution of RD, was a significant predictor of DRFS, and can be used to define categories of near-complete response and chemotherapy resistance.