356P Prognostic value of the residual cancer burden after neoadjuvant chemotherapy for invasive lobular breast cancer: An international pooled cohort study

Residual Cancer Burden (RCB) after neoadjuvant chemotherapy (NAC) has been validated to predict event-free survival (EFS) across breast cancer subtypes but its prognostic ability has not been specifically studied for invasive lobular carcinoma (ILC). We studied patient-level data (histologic subtype, RCB, and EFS) from a previously published pooled cohort from 12 institutions in the US and Europe. ILC was defined by local institutional protocols. Characteristics in pure ILC vs. non-ILC were compared using t-test or chi-squared test. Associations between continuous RCB index and EFS were assessed in both groups with mixed effect Cox models and multivariable analyses. Recursive partitioning was used in an exploratory model to stratify prognosis by individual clinicopathologic variables and the components of RCB. Of 5161 patients, the diagnosis was ILC in 216 (4.2%) and non-ILC in 4945. ILC cases were older, had lower grade, higher tumor (T) category, and more hormone receptor (HR) positive HER2 -negative subtype (73.6% vs 36.4%) (all p-values <0.05). Pathologic complete response (pCR/RCB 0) was achieved in 10.6% of ILCs and 33.4% of non-ILC (2.5% and 11.8% respectively among HR+HER2- cases, p<0.0005). Increased RCB index was significantly associated with worse EFS in both ILC and non-ILC (p<0.05) and remained prognostic when adjusted for age, grade, T category, baseline nodal status, and receptor subtype. While continuous RCB index had a linear relationship with probability of EFS event (log scale) in non-ILC, this relationship was non-linear in ILC cases; for ILC, prognosis was similar for RCB index ≤1.9, with increasing risk for RCB index >1.9. Recursive partitioning demonstrated residual tumor cellularity as most prognostic in ILC, followed by number of positive nodes and tumor dimensions. While pCR rate after NAC is low in ILC, RCB retains prognostic value, with residual cellularity providing the most information. RCB index values ≤1.9 had similar prognosis to pCR. These results underscore the utility of RCB for evaluating NAC response in those with ILC for clinical management and as an endpoint for clinical trials.