Human epidermal growth factor 2 (HER2) in early stage uterine serous carcinoma: A multi-institutional cohort study.

Gynecologic oncology 2020 Oct

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Human epidermal growth factor receptor 2 (HER2) has emerged as an important prognostic and therapeutic target in advanced stage and recurrent uterine serous carcinoma (USC). The significance of tumoral HER2 expression in early-stage disease has not been established. This multi-center cohort study included women with stage I USC treated from 2000 to 2019. Demographic, treatment, recurrence, and survival data were collected. Immunohistochemistry (IHC) was performed for HER2 and scored 0-3+. Equivocal IHC results (2+) were further tested with fluorescence in-situ hybridization (FISH). HER2 positivity was defined as 3+ IHC or FISH positive. One hundred sixty-nine patients with stage I USC were tested for HER2; 26% were HER2-positive. There were no significant differences in age, race, stage, adjuvant therapy, or follow-up duration between the HER2-positive and negative cohorts. Presence of lymph-vascular space invasion was correlated with HER2-positive tumors (p = .003). After a median follow-up of 50 months, there were 43 (25.4%) recurrences. There were significantly more recurrences in the HER2-positive cohort (50.0% vs 16.8%, p < .001). HER2 positive tumors were associated with worse progression-free (PFS) and overall survival (OS) (p < .001 and p = .024). On multivariate analysis, HER2 positive tumors were associated with inferior PFS (aHR 3.50, 95%CI 1.84-6.67; p < .001) and OS (aHR 2.00, 95%CI 1.04-3.88; p = .039) compared to HER2-negative tumors. Given its significant association with worse recurrence and survival outcomes, HER2 positivity appears to be a prognostic biomarker in women with stage I uterine serous carcinoma. These data provide support for clinical trials with anti-HER2-directed therapy in early-stage disease. Copyright © 2020 Elsevier Inc. All rights reserved.

Citation

Britt K Erickson, Omar Najjar, Shari Damast, Adriana Blakaj, Joan Tymon-Rosario, Maryam Shahi, Alessandro Santin, Molly Klein, Michelle Dolan, Ashley Cimino-Mathews, Natalia Buza, J Stuart Ferriss, Rebecca L Stone, Mahmoud Khalifa, Amanda N Fader. Human epidermal growth factor 2 (HER2) in early stage uterine serous carcinoma: A multi-institutional cohort study. Gynecologic oncology. 2020 Oct;159(1):17-22