Conventional Pathology Versus Gene Signatures for Assessing Luminal A and B Type Breast Cancers: Results of a Prospective Cohort Study.

In this study, in estrogen receptor positive (ER+) early stage breast cancer patients who were considered candidates for 70-gene signature (70-GS, "MammaPrint") use, we compared molecular subtyping (MS) based on the previously validated 80-gene signature (80-GS, "BluePrint") versus surrogate pathological subtyping (PS). Between 1 January 2013 and 31 December 2015, 595 clinical intermediate risk ER+ early stage breast cancer patients were enrolled. Hormone receptor (HR) and HER2 receptor status were determined by conventional pathology using immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH). Ki67 was assessed in a subset of patients. The overall concordance between PS and MS for luminal type cancers (A and B together) was 98%. The concordance between PS and MS for luminal A and luminal B type cancers based on the Bloom Richardson histological grade (BR) ( 586) or Ki67 ( 185) was low: 64% (Kappa 0.20 [95% CI 0.11⁻0.28]) and 65% (Kappa 0.22 [95% CI 0.062⁻0.37]), respectively. In this prospective study (NCT02209857) of a selection of ER+ and predominantly HER2- early-stage breast cancer patients, the additional ability of the 80-GS to distinguish between luminal, HER2-type and basal-like cancers was inherently very limited. The distinction of luminal-type tumors into A and B according to Ki67 status or BR grade versus the 70-GS revealed poor concordance.