Classism.

Top Line: We all know response to neoadjuvant treatment is a harbinger of disease outcomes to come, but how much can we learn from each individual case?

The Study: I-SPY2 is back with more robust analyses than ever. Remember, in this trial 938 women with breast tumors >2.5 cm with high-risk receptor status (i.e. ER <5% or Her2+) and/or high-risk genomic scores (via MammaPrint) were randomly assigned to neoadjuvant paclitaxel or one of ten investigational agents x 12 weeks then cyclophosphamide/doxorubicin x 12 weeks followed by surgery. This report doesn’t delve into the outcomes with each investigational treatment per se but rather into whether pathologic response to neoadjuvant therapy can prognosticate on a spectrum. As it turns out, event-free survival was significantly worse with each increase in residual cancer burden (RCB) class at time of surgery. Several pathologic factors assign an RCB class 0-III—don’t worry, there’s an online calculator. More interesting, this was clearly the case across every subtype, even ER+/HER2- where there was a HR 1.75 for recurrence and/or death with each increase in RCB class. Granted that subtype was least likely to achieve complete (class 0) or near complete (class I) responses. Figures 1 and 2 provide really nice visuals at glance for the outcomes presented here. The most important reason to take note of these fascinating results is that they may shine light on who is likely to benefit most from further systemic therapy post-operatively.

TBL: “Residual cancer burden as a continuous response measure exhibits favorable attributes for neoadjuvant trials in breast cancer, providing additional information beyond pathologic complete response rate and pretreatment disease characteristics.” | Symmans, JAMA Oncol 2021