Recent studies have demonstrated independent validation of the prognostic relevance of residual cancer burden (RCB) after neoadjuvant chemotherapy. However, a pooled subject-level analysis of multiple cohorts is needed to determine estimates of long-term prognosis for each class of RCB in each phenotypic subtype of breast cancer to better inform on patient outcomes. Also, a pooled subject-level analysis allows more detailed analyses of generalizability of the prognostic meaning of RCB assessments in a broader experience of practice settings.
RCB status with relevant stage, demographic and follow-up data from 10 institutes/trials (Institut Curie, Instituto de Investigación Sanitaria Gregorio Marañón, I-SPY TRIALs, Mayo clinic, MD Anderson Cancer Center, Netherlands Cancer Institute, University of Cambridge, University of Edinburgh, University of Kansas, Yale University), totaling X individual patients will be included. Median follow-up is Y years. The association between the continuous RCB index and event-free survival (EFS), as well as distant recurrence free survival (DRFS) will be assessed using mixed effect Cox models with the incorporation of random RCB coefficients to account for between-study heterogeneity. We will also allow for differences in baseline hazard across biological breast cancer subtypes and, if needed, across studies as well. In addition to this stratified mixed effect model, a multivariate analysis adjusting for age, T-category, nodal status and grade will be performed. Association between categorical RCB classes with EFS and DRFS will be similarly assessed. In addition, mixed effect Cox models will be employed to evaluate association between RCB index and class with EFS and DRFS within each HR/HER2 subtype.
We currently have centrally collected data from 4 institutes/trials from ~2500 patients and collection of the additional data of 6 institutes/trials is in process. Prognostic value of RCB in the univariate and multivariate models, overall and within subtypes, will be reported once all the data is collected and analyzed. We anticipate reporting on a pooled analysis with median follow-up of approximately 5 years.