Distribution of the PAM50 breast cancer subtypes within each pathology-based group: a combined analysis of 15,339 patients across 29 studies

Abstract

Background: Current classification of breast cancer in the clinical setting is based on pathology-based biomarkers such as hormone receptors (HR) and HER2. More recently, identification of the intrinsic molecular subtypes (IS) within each pathologybased group (i.e. HR+/HER2-, HR+/HER2+, HR-/HER2+ and triple-negative [TN]) is revealing clinical value. The objective of this study is to assess the distribution of the IS within each pathology-based group in a large series of breast cancer. Method(s): Twenty-nine studies were identified from the literature (2009-2017) in which IS and pathology-based data were reported. HR was evaluated by immunohistochemistry (IHC) and HER2 by IHC and/or FISH according to standard criteria. Pathology-based groups were divided into 4 groups: HR+/HER2-, HR+/HER2+, HR-/HER2+and TN. IS (Luminal A [LumA], Luminal B [LumB], HER2-enriched [HER2-E], Basal-like [BL] and Normal-like) were identified using the research-based, or the standardized, PAM50 gene expression-based assay. Result(s): PAM50 and pathology data was available in 15,339 patients. The distribution of the PAM50 IS within each IHC-based group is shown in Table 1. Within HR+/ HER2- group (n=9,768), non-luminal subtypes (HER2-E and BL) represented 5.6% and 2.2%, respectively. Within HR+/HER2+ group (n=1,727), HER2-E and BL represented 29.2% and 2.1%, respectively. Within HR-/HER2+ group (n=1,332), non- HER2-E subtypes (Luminal A/B and BL) represented 9.3% and 13.8%, respectively. Finally, within TN (n=2,512), non-BL subtypes (Luminal A/B and HER2-E) represented 5.9%and 11.1%, respectively. Conclusion(s): Our results confirm previous observations that all IS are represented within each pathology-based group. Based on our observations, future clinical trials in unselected breast cancer patient populations should be sufficiently powered to address the prognostic and predictive ability of the IS. (Table Presented).