The researchers from the The University of Texas MD Anderson Cancer Center evaluated HER2 expression by immunohistochemistry (IHC) in 4701 patients with different solid tumours. HER2-low expression, defined as 1-2+ by IHC was common across many solid tumours (41.1%). Furthermore, a significant number of patients without HER2 alterations (35.7%) had HER2 expression (\u22651+).<\/p>\n
The findings suggest that many patients with HER2-low solid tumours might benefit from HER2-targeted therapies. The study team led by Ecaterina Dumbrava, Assistant Professor in the Department of Investigational Cancer Therapeutics published the findings on 22 August 2023 in the Annals of Oncology<\/em>.<\/p>\n HER2 overexpression or amplification is a validated prognostic and predictive biomarker in breast and gastric\/gastro-oesophageal (GEJ) cancers. Several HER2-targeted agents have been approved and improved outcomes for patients with HER2-driven malignancies. Recently, trastuzumab deruxtecan was approved for the treatment of HER2-low (defined as IHC 1+ or IHC 2+\/in situ hybridisation [ISH]-negative) breast cancer and for non-small cell lung cancer (NSCLC) with HER<\/em>2<\/em> mutations. <\/p>\n The authors wrote in the background that HER2 status classification has been evolving and while there are clear ASCO\/CAP guidelines for breast and gastric cancers, other tumour types have no clear guidelines for testing. Classically, HER2 positivity is defined as overexpression by IHC or HER<\/em>2<\/em> gene amplification by ISH. Most recently HER2-low is a newly defined category with HER 1+ or 2+ expression by IHC and lack of HER2<\/em> gene amplification measured by ISH. These patients have been previously considered HER2-negative.<\/p>\n The frequency of HER2-low expression is unknown across solid tumours. Furthermore, the changes in HER2-low expression status between primary and metastatic samples are unknown. The association between the HER2<\/em> genomic alterations and HER2 expression also remains unknown. To address these gaps, the authors studied a large cohort of patients with solid tumours and evaluated their HER2 expression. They also sought to assess changes in HER2 status between paired primary and metastatic breast and gastric\/GEJ cancer samples.<\/p>\n HER2 expression was evaluated by IHC in 4701 patients with solid tumours. The study team evaluated the HER2 expression by IHC and amplification by ISH in paired breast and gastric\/GEJ primary and metastatic samples. HER2 expression was correlated with HER<\/em>2<\/em> genomic alterations evaluated by next-generation sequencing (NGS) in non-breast, non-gastric\/GEJ samples.<\/p>\n HER2 expression (HER2 IHC 1-3+) was found in half (49.8%) of cancers, with HER2-low (ICH 1 or 2+) found in many tumour types: 47.1% in breast, 34.6% in gastric\/GEJ, 50.0% in salivary gland, 46.9% in lung, 46.5% in endometrial, 46% in urothelial and 45.5 % of gallbladder cancers.<\/p>\n The concordance evaluation of HER2 expression between primary and metastatic breast cancer samples, showed that HER2 3+ remained unchanged in 87.1% with a strong agreement between primary and metastatic samples, with a weighted kappa of 0.85 (95% confidence interval 0.79-0.91). <\/p>\n HER<\/em>2<\/em> alterations were identified in 117 patients (7.5%) with non-breast, non-gastric\/GEJ solid tumours who had NGS testing. Of 1436 patients without HER<\/em>2<\/em> alterations, 512 (35.7%) showed any level of HER2 expression by IHC.<\/p>\n The authors commented that a more tumour agnostic analysis of HER2 expression is warranted given the recent FDA approval of HER2-targeted treatments for HER2-low breast cancer and NSCLC with HER<\/em>2<\/em> mutations and the inclusion in NCCN guidelines of HER2-targeted therapies for non-breast and non-gastric\/GEJ tumour types including colon, salivary gland, and biliary truct cancers.<\/p>\n This is the first study to report on HER2-low expression in a large cohort of patients across multiple solid tumour types who underwent HER2 testing for personalised cancer therapy. Changes in HER2 status between paired primary and metastatic breast and gastric\/GEJ samples provide insight into the potential role for re-testing of HER2 expression. Further prospective research is needed to evaluate the clinical outcomes by tumour types and HER2 expression status.<\/p>\n This work was supported by the Strategic Alliance: Sanofi\u2212MD Anderson Cancer Center HER2 T-Cell Engager Project Collaboration, MD Anderson Cancer Center Support grant from US NIH\/NCI, Center for Clinical and Translational Science award.<\/p>\nReference<\/h3>\n