Intrinsic molecular subtypes of breast cancers categorized as HER2-positive using an alternative chromosome 17 probe assay

Abstract The 2013 update of the American Society of Clinical Oncology-College of American Pathologists (ASCO-CAP) human epidermal growth factor receptor 2 (HER2) testing guidelines recommend using an alternative chromosome 17 probe assay to resolve HER2 results determined to be equivocal by immunohi...
Ausführliche Beschreibung

Abstract The 2013 update of the American Society of Clinical Oncology-College of American Pathologists (ASCO-CAP) human epidermal growth factor receptor 2 (HER2) testing guidelines recommend using an alternative chromosome 17 probe assay to resolve HER2 results determined to be equivocal by immunohistochemistry (IHC) or fluorescence in-situ hybridization (FISH). However, it is unclear if cases considered HER2-positive ($ HER2^{+} $) by the alternative probe method are similar to those classified as $ HER2^{+} $ by traditional IHC and FISH criteria and benefit the same from HER2-targeted therapies. We studied the clinical and pathologic features of all 31 breast cancers classified as $ HER2^{+} $ by the alternative probe method at our institution since 2013 and determined their PAM50 intrinsic molecular subtypes. For comparison, we analyzed 19 consecutive cases that were classified as $ HER2^{+} $ by traditional FISH criteria during the same time period. Thirty (97%) cancers in the alternative probe cohort were estrogen receptor (ER)-positive ($ ER^{+} $), while only 9/19 (47%) of traditional HER2 controls were $ ER^{+} $ (p = 0.0002). Sufficient tissue for intrinsic subtype analysis was available for 20/31 cancers in the alternative probe cohort and 9/19 in the traditional $ HER2^{+} $ group. None (0%) of the 20 alternative probe-positive cases were of the HER2-enriched intrinsic subtype, while 8/9 (89%) of those $ HER2^{+} $ by traditional FISH criteria were HER2-enriched (p = 0.0001). These findings suggest that breast cancers classified as $ HER2^{+} $ only by the alternative probe method are biologically distinct from those classified as $ HER2^{+} $ by traditional criteria, and raises questions as to whether or not they derive the same benefit from HER2-targeted therapies. Ausführliche Beschreibung