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

Britt K. Erickson, Omar Najjar, Shari Damast, Adriana Blakaj, Joan Tymon-Rosario, Maryam Shahi, Alessandro Santin, Molly E Klein, Michelle M Dolan, Ashley Cimino-Mathews, Natalia Buza, J. Stuart Ferriss, Rebecca L. Stone, Mahmoud A Khalifa, Amanda N. Fader

Research output: Contribution to journalArticle

Abstract

Background: 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. Methods: 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. Results: 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. Conclusions: 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.

Original languageEnglish (US)
JournalGynecologic oncology
DOIs
StateAccepted/In press - 2020

Keywords

  • Biomarkers
  • Human epidermal growth factor receptor 2 HER2
  • Uterine serous carcinoma

PubMed: MeSH publication types

  • Journal Article

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    Erickson, B. K., Najjar, O., Damast, S., Blakaj, A., Tymon-Rosario, J., Shahi, M., Santin, A., Klein, M. E., Dolan, M. M., Cimino-Mathews, A., Buza, N., Ferriss, J. S., Stone, R. L., Khalifa, M. A., & Fader, A. N. (Accepted/In press). Human epidermal growth factor 2 (HER2) in early stage uterine serous carcinoma: A multi-institutional cohort study. Gynecologic oncology. https://doi.org/10.1016/j.ygyno.2020.07.016