The leftovers.

Top Line: We know that a pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) is prognostic of improved survival outcomes for patients with breast cancer, but, for the majority of patients who don’t have a pCR, is the extent of residual disease still prognostic of outcome?

The Study: Residual cancer burden (RCB) is a standardized measure of residual disease after NAC. RCB is calculated as a continuous number based on the size and proportion of residual primary tumor and the number and size of nodal metastases. Cut-points are also used to group RCB scores into four classes ranging from RCB-0 (pCR) to RCB-3. This analysis of patient-level data from >5000 patients pooled from 12 centers or clinical trials (including ISPY-1 and ISPY-2) sought to determine the prognostic significance of RCB within different breast cancer subtypes. 37.9% were hormone receptor positive (HR+)/HER2-, 27.7% were HER2+ (60% HR+, 40% HR-), and 34.4% were triple negative (TNBC). The RCB class breakdown was 32.5% RCB-0 (pCR), 12.8% RCB-1, 39.1% RCB-2, and 15.6% RCB-3. Overall, RCB score, RCB class, T3-4 disease, grade 3 disease, and lymph node positivity were associated with event-free (EFS) and distant relapse-free survival (DRFS). There was a near linear relationship between RCB and the log relative hazard rate for EFS and DRFS. RCB was also significantly associated with EFS and DRFS in all receptor subgroups with a hazard ratio per unit increase in RCB of 1.55 for HR+/HER2- disease and up to 2.16 for HR-/HER2+ disease. Within subgroups, the linear relationship between RCB and survival held true with the exception of HR+/HER2- disease. In the HR+/HER2- subgroup this nonlinearity was driven by similar survival outcomes for both RCB-0 and RCB-1 classes. The association of RCB with outcome for HR+/HER2- disease was not strong until reaching RCB classes 2 and 3. Important to note is that most events involved distant metastasis–meaning the response of primary and nodal disease has important implications for the response of potential systemic disease. It would also be interesting to know how RCB is associated with radiation benefit overall and among subgroups. 

TBL: Residual cancer burden (RCB) provides important prognostic information for patients with breast cancer who don’t achieve a pathologic complete response to neoadjuvant chemotherapy. | Yau, Lancet Oncol 2021


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