Dr Hacker on the Proportion of HER2-Expressing Tumors in Endometrial Cancer

Kari E. Hacker, MD, PhD, assistant professor, Department of Obstetrics and Gynecology, NYU Grossman School of Medicine, NYU Langone Health, discusses the proportion of endometrial cancers that are HER2-expressing and eligible for treatment with HER2-targeted antibody-drug conjugates (ADCs).

Hacker and colleagues conducted a retrospective, single-institution study examining 147 patients who underwent hysterectomy for endometrial cancer between December 2022 and January 2024. The study utilized HER2 immunohistochemistry (IHC) testing for all patients with endometrial cancer, supplemented with reflex FISH testing for 2+ IHC in p53 aberrant endometrial cancers and specific scenarios for p53 wild-type disease. HER2 positivity was determined by 3+ staining or 2+ staining with FISH amplification, while HER2-low was defined as 1+ on IHC or 2+ without FISH amplification. Among the 124 tumors tested, approximately two-thirds displayed HER2 positivity by IHC, with approximately 30% exhibiting 2+ or 3+ staining. This potentially makes these patients candidates for targeted therapy, Hacker says.

The analysis revealed that 62.1% of tumors expressed HER2, including 37.9%, 32.3%, 25% and 4.8% of patients with IHC 0+, 1+, 2+ and 3+ staining, respectively, Hacker reports. Moreover, results showed HER2 positivity across all molecular subtypes and histologies, with a notable correlation observed between HER2 positivity and non-endometrioid histology, she adds. Additionally, patients diagnosed at advanced stages were more likely to exhibit HER2 positivity compared with those diagnosed at early stages, at 92% vs 55%, respectively (P = .0005), Hacker details. Based on these data, one-third of unselected endometrial cancers with recurrent disease would qualify for treatment with fam-trastuzumab deruxtecan-nxki (Enhertu) according to current National Comprehensive Cancer Center guidelines.

These findings underscore the importance of assessing HER2 status in endometrial cancer patients regardless of histology or molecular subtype, suggesting a substantial proportion of tumors may benefit from targeted HER2-directed therapies, Hacker emphasizes.