Abstract P4-05-09: Clinicopathologic characteristics and molecular profiling of HER2-low breast cancer: A single academic institution experience
Authors: Zhang Huina , Katerji Hani , Turner Bradley M , Hicks David G 
Published: March 2022

Abstract
Objectives: Recently-published phase I clinical trials have demonstrated promising efficacy of novel HER2-targeted therapy in advanced breast cancers with a HER2 immunohistochemistry (IHC) score of 1+, or 2+ with a non-amplified in-situ hybridization (ISH). This has raised the possibility for changing the categories for clinical interpretation of HER2 in breast cancers into: 1) HER2-negative (HER2 IHC score of 0+), 2) HER2-low (IHC score of 1+, or 2+ with a non-amplified ISH), and 3) HER2-positive (HER2 IHC score of 3+ and IHC score of 2+ with amplified ISH). Earlier studies on low HER2-expressing breast cancers focused on differences between HER2 2+ with negative ISH and HER2 0/1+. The aims of this study are to investigate the clinical, pathologic and molecular features of HER2-low breast cancers, in comparison to HER2-negative breast cancers. Methods: 281 breast cancers with HER2 IHC were diagnosed between 04/2020 and 12/2020 at our institution, including 164 HER2-negative, 87 HER2-low, and 30 HER2-positve cases. The clinicopathologic information and molecular subtyping (Agendia BluePrint) results of HER2-low breast cancers were retrospectively collected, and compared to those of HER2-negative cases. A p-value of &lt; 0.05 was considered statistically significant. Results: HER2-low breast cancers accounted for 31% (87/281) of breast cancers in our study population. The majority of these HER2-low cases were clinical stage I-II, with 6 cases (6.9%) being stage IV. Most of the HER2-low cancers had a HER2 IHC score of 1+ (87%, 76/87), a ductal phenotype (82%, 71/87), histologic grades of 1 or 2 (94%, 82/87), were ER positive (94%, 81/86), PR positive (86%, 74/86), and had luminal molecular subtypes (96%, 83/87). Four patients received neoadjuvant chemotherapy and none of them achieved pathologic complete response. Compared to HER2-negative cancers, HER2-low breast cancers showed a lower Ki-67 (p&lt;0.05), a higher ER positivity (p&lt;0.05), a higher pathologic stage (p&lt;0.05), and were more likely to be of the luminal molecular subtype (p&lt;0.05). There was no significant difference in age, tumor size, histologic type, histologic grade, presence of lymphovascular invasion, PR status, or pathologic nodal stage (Table 1). Conclusions: HER-2 low breast cancers represent a heterogeneous group, and the majority are lower grade, early-stage, hormonal receptor positive, have a HER2 IHC score of 1+, and have a luminal molecular phenotype. This study provides the baseline clinicopathologic and molecular features of HER2-low breast cancers. Additional studies are needed to further elucidate the biology of HER2-low breast cancers.
Table 1. Comparison of clinicopathologic parameters and molecular subtypes between HER2-low and HER2-negative breast cancersHER2-Low (n=87)HER2-Negative (n=164)P valueAge (year)66.6264.380.22Tumor size (mm)21.4919.290.49Histologic typeDuctal711390.57Lobular1524Mixed11Histologic grade143640.156239813519pT Stage142880.0452817362Unknown2735PN stage036760.351613210300Unknown2353ER positivity94.2 % (81/86)82.9% (136/64)0.01PR positivity86% (74/86)76.8% (126/164)0.09Ki-67 (%)12.8118.290.03Molecular subtypeLuminal A571050.003Luminal B2630HER210Basal328
Citation Format: Huina Zhang, Hani Katerji, Bradley M Turner, David G Hicks. Clinicopathologic characteristics and molecular profiling of HER2-low breast cancer: A single academic institution experience [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-05-09.