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Uterine serous carcinoma: key advances and novel treatment approaches
  1. J Stuart Ferriss1,
  2. Britt K Erickson2,
  3. Ie-Ming Shih3 and
  4. Amanda N Fader1
  1. 1Kelly Gynecologic Oncology Division, Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
  2. 2Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Minnesota, Minneapolis, Minnesota, USA
  3. 3TeLinde Gynecologic Pathology Program, Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
  1. Correspondence to Dr J Stuart Ferriss, Department of Gynecology and Obstetrics, Johns Hopkins University, Baltimore, MD 21218, USA; jferris3{at}jhmi.edu

Abstract

The incidence and mortality rates from endometrial cancer continue to increase worldwide, while rates in most other cancers have either plateaued or declined considerably. Uterine serous carcinoma represents a fraction of all endometrial malignancies each year, yet this histology is responsible for nearly 40% of all endometrial cancer-related deaths. These deaths disproportionately affect black women, who have higher rates of advanced disease at diagnosis. Molecular genetic analyses reveal major alterations including TP53 mutation, PIK3CA mutation/amplification, ERBB2 amplification, CCNE1 amplification, FBXW7 mutation/deletion, PPP2R1A mutation, and somatic mutations involving homologous recombination genes. Clinical risk factors for uterine serous carcinoma include advancing age, a history of breast cancer, tamoxifen usage, and the hereditary breast–ovarian cancer syndrome. Surgery remains the cornerstone of treatment. Recent advances in our understanding of uterine serous carcinoma molecular drivers have led to development of targeted therapeutics that promise improved outcomes for patients. Overexpression or amplification of HER2 in uterine serous carcinoma carries a poor prognosis; yet this actionable target has led to the incorporation of several anti-HER2 therapies, including trastuzumab which, when added to conventional chemotherapy, is associated with improved survival for women with advanced and recurrent HER2-positive disease. The combination of pembrolizumab and lenvatinib is also a promising targeted treatment strategy for women with uterine serous carcinoma, with a recent phase II study suggesting a 50% response rate in women with recurrent disease. Several trials examining additional targeted agents are ongoing. Despite years of stalled progress, meaningful, tailored treatment options are emerging for patients with this uncommon and biologically aggressive endometrial cancer subtype.

  • uterine cancer
  • surgery
  • SLN and lympadenectomy
  • pathology

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Footnotes

  • Twitter @amandanfader

  • Contributors All authors made substantial contributions to the conception, drafting, critical revision, and have given their approval of the manuscript. All authors agree to be accountable for all aspects of the work.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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