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

8 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:
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.

Publisher Copyright:
© 2020 Elsevier Inc.

Keywords

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

PubMed: MeSH publication types

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

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