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 Klein, Michelle Dolan, Ashley Cimino-Mathews, Natalia Buza, J. Stuart Ferriss, Rebecca L. Stone, Mahmoud Khalifa, Amanda N. Fader

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

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)
Pages (from-to)17-22
Number of pages6
JournalGynecologic oncology
Volume159
Issue number1
DOIs
StatePublished - Oct 2020

Bibliographical note

Funding Information:
Research reported in this publication was supported to BKE by the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health , United States under Award Number K12HD055887 and to ADS by R01 CA154460-01 and U01 CA176067-01A1 grants from NIH , the Deborah Bunn Alley Foundation , the Tina Brozman Foundation , the Discovery to Cure Foundation, the Guido Berlucchi Foundation and the Stand-up-to cancer (SU2C) convergence grant 2.0 to ADS. Additional support was received from the Stolz Family Fund and the Kosegarten Family Fund . The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health .

Funding Information:
ANF is a consultant for Merck. BKE is a consultant for Boston Scientific and receives research funding from Clovis oncology. RLS is a consultant for Astra Zeneca. AS receives research funding from Puma, Immunomedics, Gilead, Synthod, Merck, Boehinger-Ingelheim, Genentech, and Tesaro. ACM receives research funding and is a consultant for Bristol-Myers Squibb.

Keywords

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

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

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