Background: The RS assay is widely used to guide treatment decisions in ER+ HER2-negative early BC regardless of tumor histology. However, the RS validation studies did not include an analysis by histologic subtype. We investigated treatments/clinical outcomes in RS-tested Clalit Health Services (CHS) patients (pts) by histologic subtype, focusing on invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC). Methods: This exploratory analysis of the CHS cohort included BC pts with N0/N1mi/N1 disease who were RS-tested from 1/2006 through 12/2010 (N0) or 12/2011 (N1mi/N1). Data from medical records were analyzed to assess risks of distant recurrence and BC death by histologic subtype. Results: The cohort included 2510 pts: 2060 (82%) IDC, 298 (12%) ILC, and 152 (6%) unknown/others. Median follow up for IDC/ILC pts was 6.0/6.1 yrs. Median age in IDC/ILC pts was 60/62 yrs; median tumor size was 1.5/1.8 cm; 71%/71% were N0, and 29%/29% were N1mi/N1. RS distribution (<18, 18-30, ≥31) was 50%, 39%, and 11%, respectively for IDC pts and 48%, 48%, and 4%, respectively, for ILC pts. Chemotherapy (CT) use for each RS group was similar between IDC and ILC pts; 5-yr Kaplan-Meier estimates for the risk of distant recurrence and BC death differed significantly across RS groups in both IDC and ILC; clinical outcomes for IDC and ILC pts were similar within risk groups see Table. Conclusions: For both IDC and ILC pts, treatment was aligned with the RS results. Within each RS group, there was no difference in clinical outcomes between these histologic subtypes, however the number of pts with ILC and RS≥31 was limited.

*Distant recurrence risk/BC death in RS groups was compared using Log-rank test.