Distribution and concordance of HER2 scores in endometrial and ovarian cancer.

Objectives: Although multiple HER2 scoring criteria exist, the optimal strategy to identify patients with gynecologic malignancies who may benefit from HER2-directed therapies remains unknown. The objectives of this study were to assess the distribution and concordance of HER2 scores in endometrial and ovarian cancer.

Methods: One hundred five tumor specimens from 94 patients with endometrial or epithelial ovarian cancer (EOC) who underwent Caris tumor profiling from 11/2022 to 01/2025 were identified from a retrospective database. Each sample was assigned a HER2 immunohistochemistry (IHC) score of 0, 1+, 2+, or 3+ using breast, endometrial, and gastric criteria. ERBB2 amplification and HER2 IHC scores were abstracted from Caris reports. Patient characteristics and HER2 score distributions were analyzed using descriptive statistics and Fisher's exact test. Matrix correlation coefficients were used to assess HER2 score concordance.

Results: A total of 105 samples underwent internal triplicate HER2 scoring - 63 EOC and 42 endometrial. A higher percentage of patients with endometrial cancer were HER2-high compared to those with EOC (45.2-50 % vs 20.6 %, p < 0.05). Internal triplicate HER2 score concordance was strong (r ≥ 0.96, p < 0.001) but weaker when compared to Caris scores (r = 0.66). Of the 23 discordant HER2 results, 13 would have changed therapy eligibility (56.5 %). Only 12 patients (12.7 %) had intermediate or high ERBB2 amplification.

Conclusions: A clinically significant percentage of patients had HER2-high tumors regardless of tumor type. HER2 score concordance was strong within each sample but weaker when compared to Caris scores. Incorporating multi-site testing and/or validation of external IHC into any gynecologic HER2 scoring algorithm should be considered.