Dr Machaalani on the Incidence of ERBB2 Amplifications Across Race, Sex, and Cancer Type

Marc Machaalani, MD, research fellow, Department of Medicine, Dana-Farber Cancer Institute, discusses an investigation into the distribution of ERBB2 (HER2) amplifications across sex, race, and cancer type in patients with cancer. Notably, findings from this analysis were presented at the 2024 ESMO Congress.

In April 2024, fam-trastuzumab deruxtecan-nxki (Enhertu) received accelerated approval from the FDA for the treatment of patients with pretreated, metastatic or unresectable HER2-positive tumors. Machaalani and colleagues investigated the distribution of ERBB2 amplifications, often linked to HER2 overexpression, across various subgroups of patients with cancer based on race, sex, and cancer type. Investigators analyzed data from 103,786 patients within the Genomics Evidence Neoplasia Information Exchange (GENIE) registry and identified ERBB2 amplifications in 4.02% of samples (n = 5040), with the highest rates observed in esophageal adenocarcinoma (19.4%), breast cancer (12%), salivary gland cancer (7.2%), bladder cancer (6.1%), and endometrial cancer (4.7%), he explains.

Significant differences emerged across subgroups, he continues. For example, male patients with esophagogastric cancer exhibited higher rates of ERBB2 amplifications compared with female patients with these diseases, at 14.8% vs 9.5%, respectively. Conversely, female patients with breast cancer had higher rates of ERBB2 amplifications than their male counterparts, Machaalani reports. Racial disparities were also observed, with Asian patients with colorectal and bladder cancers showing 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 vs White patients with this disease, he expresses.

Additionally, ERBB2 amplifications were more frequently detected in metastatic tumors compared with primary tumors, with notable findings in vaginal cancers, Machaalani continues. 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, he states. By acknowledging these differences, oncologists can better tailor treatment approaches, improving outcomes in patients with HER2-positive tumors, according to Machaalani. Furthermore, these insights are valuable for guiding clinical trial designs, ensuring they account for the variability in HER2 amplification across different demographics and tumor types, Machaalani says. This study underscores the need for personalized therapeutic strategies to optimize care for diverse patient populations, he concludes.