Quantitative hormone receptors, triple-negative breast cancer (TNBC), and molecular subtypes: A collaborative effort of the BIG-NCI NABCG.

Abstract

1008 Background: Most TNBC trials focusing on biology of the basal-like subtype (BLBC) allow borderline (1-10% staining) estrogen receptor (ER) and progesterone receptor (PgR) expression by immunohistochemistry (IHC); however the optimal ER and PgR cut points to enrich for non-luminal subtypes has not been studied. In this study,we compared quantitative ER/PgR status with gene expression-based intrinsic subtype in order to determine if borderline cases should be included in TNBC trials. Methods: ER, PgR, and HER2 status was determined by central review of tumors collected from three phase III randomized trials: GEICAM 9906 (n=820), NCIC CTG MA.5 (n=476) and MA.12 (n=398). PAM50 intrinsic subtyping (BLBC, HER2-enriched, Luminal A, Luminal B and Normal-like) was performed using the qRT-PCR-based assay. Quantitative ER/PgR expression by IHC and subtype was tested using ANOVA and Fisher’s exact test. Results: Of 1,694 tumors, 15% were BLBC, 21% HER2-Enriched, 33% Luminal A, 25% Luminal B and 4% Normal-like. BLBC subtypes were significantly associated with low expression of ER and PgR (median = 0.05%) compared to other subtypes (p < 0.001). The vast majority of BLBC (96%) did not express any ER or PgR protein by IHC. BLBC represented 73% of TNBC (borderline cases not included) and significantly more than the additional TNBC with borderline ER/PgR (p < 0.001). Within borderline ER/PgR and HER2-negative cases only, 17% were BLBC and 46% were luminal subtypes (Table). Conclusions: BLBC rarely express ER or PgR by IHC. The majority of borderline TNBC (1-10% ER/PgR) are not BLBC; half of them are categorized as luminal categories that may be endocrine sensitive. TNBC trials seeking to target BLBC tumor biology should use the ASCO/CAP guidelines of 0% as the cutoffs for ER and PgR negativity. [Table: see text]