HER2 Amplification Varies Significantly Across Cancers and Patient Subgroups, Study Finds

• Analysis of over 100,000 patients reveals that ERBB2 (HER2) amplifications vary significantly across cancer types, with highest rates in esophageal adenocarcinoma and breast cancer.
• Male patients with esophagogastric cancer show higher ERBB2 amplification rates, while female breast cancer patients also exhibit elevated rates compared to their male counterparts.
• Racial disparities exist, with Asian patients having higher ERBB2 amplification rates in colorectal and bladder cancers, and Black patients showing higher rates in endometrial cancer.
• The study highlights the need for personalized HER2-targeted therapies and tailored clinical trial designs to account for variability in HER2 amplification across demographics and tumor types.

A comprehensive analysis of over 100,000 patients has revealed significant variations in ERBB2 (HER2) amplifications across different cancer types and patient subgroups, according to research presented at the 2024 ESMO Congress. The findings, which have implications for personalized HER2-targeted therapies, underscore the importance of understanding these heterogeneities to improve patient outcomes.

Incidence of HER2 Amplification

The study, led by Marc Machaalani, MD, research fellow at Dana-Farber Cancer Institute, analyzed data from 103,786 patients within the Genomics Evidence Neoplasia Information Exchange (GENIE) registry. The researchers identified ERBB2 amplifications in 4.02% of samples (n = 5040). The highest rates were observed in esophageal adenocarcinoma (19.4%), breast cancer (12%), salivary gland cancer (7.2%), bladder cancer (6.1%), and endometrial cancer (4.7%).

Sex-Based Differences

Significant differences emerged when analyzing data by sex. Male patients with esophagogastric cancer exhibited higher rates of ERBB2 amplifications compared to female patients with these diseases (14.8% vs 9.5%, respectively). Conversely, female patients with breast cancer had higher rates of ERBB2 amplifications than their male counterparts.

Racial Disparities

Racial disparities were also evident in the analysis. Asian patients with colorectal and bladder cancers showed higher rates of ERBB2 amplifications than White and Black patients with these diseases. Furthermore, Black patients with endometrial cancer displayed higher rates of these amplifications compared to White patients with this disease.

Metastatic vs. Primary Tumors

Notably, ERBB2 amplifications were more frequently detected in metastatic tumors compared to primary tumors, with notable findings in vaginal cancers. This suggests that HER2 amplification may play a role in cancer progression and metastasis.

Implications for Personalized Therapy

"These results emphasize the importance of understanding the heterogeneity in HER2 amplification across subgroups, as it has significant implications for the personalized use of HER2-targeted therapies," said Dr. Machaalani. By acknowledging these differences, oncologists can better tailor treatment approaches, potentially improving outcomes in patients with HER2-positive tumors. The findings are also valuable for guiding clinical trial designs, ensuring they account for the variability in HER2 amplification across different demographics and tumor types. This is particularly relevant given recent approvals of HER2-targeted therapies like fam-trastuzumab deruxtecan-nxki (Enhertu), which received accelerated FDA approval in April 2024 for pretreated, metastatic or unresectable HER2-positive solid tumors. The study underscores the need for personalized therapeutic strategies to optimize care for diverse patient populations.