Abstract P4-06-09: HER2+ and HER2- luminal B subtypes have similar overall survival and histologic grade distributions
Authors: Chen Y , Kovatich AJ , Fantacone-Campbell JL , Hooke JA , Kvecher L , Kovatich AW , Gallagher CM , Hueman MT , Hyslop T , Mural RJ , Shriver CD , Rui H , Hu H 
Published: August 2014

Abstract
Background There are multiple subtypes in invasive breast cancers (IBCs). Immunohistochemistry (IHC)-based assays using ER, PR, HER2, and Ki67 for subtyping has been developed. However, association between such subtypes and treatment outcomes and histology is not completely known, and are impacted by dataset-to-dataset and pathologist-to-pathologist variations. We report an analysis on these problems, as a pilot study of a project involving 5,000 patients and 250 protein biomarkers.
Methods Patients were enrolled for the Clinical Breast Care Project from a military site with data collected per IRB-approved protocols, from 2000 to 2010. Total of 215 female IBC cases were included in this study, with surgically resected tumors (SRT) assayed for ER, PR, HER2, and Ki67 by IHC in a central CLIA-certified lab following clinical guidelines where applicable. All slides were reviewed by a single experienced breast pathologist. ER and PR was positive if nuclear staining was &gt;5%. HER2 was negative if IHC = 0 or 1+ and positive if IHC = 3+; For IHC = 2+, the FISH result determined the final call. Ki67 was positive if nuclear staining was &gt; = 15%. For IBC subtypes, LA was ER+/HER2-/Ki67-; Two LB subtypes were defined, with LB1 being ER+/HER2-/Ki67+ and LB2 being ER+/HER2+; Her2+ was ER-/PR-/HER2+; TN was ER-/PR-/HER2-. Statistical analyses were performed using SAS, Kaplan-Meier estimate and log-rank test were used for survival analysis and the follow-up period was 10 years with a median of 4.6 years. Chi-Square test was used for categorical data analysis supplemented by Fisher's Exact test as appropriate.
Results 204 of the 215 cases were classified into subtypes of LA (n = 74, 7 deceased), LB1 (n = 53, 4 deceased), LB2 (n = 14, 1 deceased), Her2+ (n = 14, 1 deceased), and TN (n = 49, 16 deceased). Despite the low number of events in some subtypes, there was a significant difference in overall survival between the 5 subtypes of IBCs defined here (p = 0.0023), with TN cases showing the least favorable outcome. No difference was observed in outcome between LB1 and LB2 (p = 0.86). Overall, Ki67+ cases trended toward worse outcomes (p = 0.08), which was also observed in TN (p = 0.17) but not other subtypes. Histologic grades were significantly different among the 5 subtypes (p = 6.25E-20); 96% of LA cases were G1 or G2, over 80% of LB1 and LB2 cases were G2 or G3, and all Her2+ and 93% of TN cases were G2 or G3. Within the luminal subtypes, grade distribution for LA cases was significantly different from that for LB cases (p&lt;0.0001) but there was no difference between LB1 and LB2 cases (p = 0.95).
Discussion In this cohort where all IHC and pathology slides were reviewed by a single pathologist, we used cell proliferation marker Ki67 to help classify luminal IBCs into LA, LB1 (HER2-), and LB2 (HER2+). Overall survival analysis result for all cases was consistent with the literature, Ki67+ cases trended toward worse outcomes, and no outcome difference was identified between LB1 and LB2. Histologic grade distributions in different subtypes were consistent with the literature; we further found no difference between LB1 and LB2 subtypes.
The views expressed in this abstract are those of the authors and do not reflect the official policy of the Department of Defense, or US Government.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P4-06-09.