Abstract PO5-24-07: HER2 EXPRESSION HETEROGENEITY PATTERN IN INVASIVE BREAST CARCINOMAS: FREQUENCY, DISTRIBUTION AND RELATION TO MORPHOLOGICAL VARIABLES
Authors: Waitzberg Angela Flavia , Barbosa Lucas de Figueiredo , Filho Adilson Monteiro dos Santos , da Cruz Ana Luiza , Nova Lisandra Gonzalez Porta , Prigenzi Karla Calaça Kabbach 
Published: May 2024

Abstract
Human epidermal growth factor receptor 2 (HER2), a critical contributor to breast cancer development, is found to be amplified and overexpressed in approximately 15-20% of cases, making it a significant factor in carcinogenesis. This scenario was targeted by anti-HER2 drugs approved by several regulatory agencies in the past 15 years. Recently, novel anti-HER2 antibody-drug conjugates (ADCs) were approved to metastatic breast cancer with some HER2 expression albeit not due to amplification of the gene. Despite being classified as HER2 negative, most of these tumors exhibit detectable amounts of HER2 protein, reinforcing the challenging task of HER2 expression evaluation. In this scenario, it is very important to evaluate the spectrum of HER2 expression within a tumor due to its heterogeneity. We designed a retrospective linear study to reanalyze all HER2 immunohistochemical core biopsy slides of patients with primary invasive breast carcinomas (IBC) diagnosed and treated at São Paulo Federal University Hospital between 2019 and 2023. Pathological variables (histological subtype, histological grading, and hormonal receptors expression) were collected in pathology reports. Only patients with available slides and blocks were enrolled. HER2 slides were evaluated by three observers in consensus to access ASCO-CAP 2018 guidelines HER2 expression; presence or absence of HER2 expression heterogeneity; pattern of heterogeneity; frequency of the primary and secondary HER2 score in heterogeneous cases; and frequency of HER2 score in cases with homogeneous expression. Statistical analyses were performed with Chi-Square and Mann–Whitney U test using SSPS (26.0) program. 353 cases were included in this study. 104 (29,5%) were under 50 years and 249 (70,5%) over 50 years. 54,1% cases were left sided and 45,9% right sided. IBC of no special type comprehended 324 cases (91,8%) and invasive lobular carcinomas (ILC) were represented by 26 cases (7,4%); less than 1% of the cases were rare subtypes. Overall, HER2 results was negative in 296 (83,9%) cases and positive in 42 (11,9%) cases; HER2 2+ accounted by 15 cases (4,2%). Out of the negative cases, 235 (79.4%) were classified as 0+ and 61 (20.6%) were classified as 1+. Homogenous HER2 expression was observed in 287 cases (81,3%) with predominance of 0+ expression (80,8% - 232 cases), followed by 1+ (9,4% - 27 cases). ITH was present in 66 cases (18,7%), in which the subtyping was represented by 39 scattered (59,1%), 25 clustered (37,9%) and 2 mosaic (3%). The most prevalent score in this group was 1+ (51,5% - 34 cases), followed by 3+ (25,8% - 17 cases); the secondary score was predominantly categorized as 0+ (58,3%), followed by 1+ (20%) and 2+ (20%); only one case showed as 3+ expression. In the ILC group, 24 cases (92,3%) exhibited homogeneous HER2 expression, with predominant 0+ score (75% - 18 cases), while 2 cases (7,7%) showed heterogeneous expression. Out of the cases with heterogeneous HER2 expression, one exhibited a clustered heterogeneity pattern, with a primary HER2 score of 1+ and a secondary score of 0+. The other case displayed a scattered heterogeneity pattern, with a primary HER2 score of 3+ and a secondary score of 2+. There was a statistically significant association between HER2 expression heterogeneity and histologic grade (p = 0.005), and a marginal association with estrogen (p = 0.060) and progesterone (p = 0.060) expression. Tumor size wasn’t associated with heterogeneity (p = 0,071). We conclude that heterogeneity is prevalent in HER2 expression, especially in IBC, and should be addressed in pathology reports, especially in the ADCs scenario.
Citation Format: Angela Flavia Waitzberg, Lucas de Figueiredo Barbosa, Adilson Monteiro dos Santos Filho, Ana Luiza da Cruz, Lisandra Gonzalez Porta Nova, Karla Calaça Kabbach Prigenzi. HER2 EXPRESSION HETEROGENEITY PATTERN IN INVASIVE BREAST CARCINOMAS: FREQUENCY, DISTRIBUTION AND RELATION TO MORPHOLOGICAL VARIABLES [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-24-07.