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Endometrial Cancer

What is Endometrial Cancer?

  • Endometrial cancer is found in the inner lining of the uterus, known as the endometrium.[i]

  • It is the most common type of cancer that affects the female reproductive organs in the US.[ii]

  • Approximately 60,000 new cases of endometrial cancer are expected to be diagnosed in the US in 2021.[ii]

What are the signs and symptoms of endometrial cancer?

The most common symptoms of endometrial cancer are:[iii],[iv],[v]

  • Abnormal vaginal bleeding

  • ~90% of women with endometrial cancer will experience abnormal vaginal bleeding such as a change in periods, bleeding between periods, or bleeding after menopause.

  • Non-bloody vaginal discharge

Additional common late-stage symptoms of endometrial cancer include:[iii],[iv],[v]       

  • Pelvic pain

  • Feeling a mass

  • Weight loss without trying

What is the unmet need in endometrial cancer?

  • The majority of women who have endometrial cancer are diagnosed early, and are cured with surgery.

  • However, for women whose disease recurs after platinum-based chemotherapy, there are limited treatment options.[vi],[vii],[viii]

  • Approximately 1 in 4 women with endometrial cancer experience a recurrence or are diagnosed with advanced disease each year.[ix],[x]

  • Endometrial cancer has the highest rate of mismatch repair deficiency (dMMR) among tumor types,[xi],[xii] at approximately 25%,xii and increased rates of recurrence have been reported for some women with dMMR endometrial cancer[xiii] resulting in an unmet need for expanded treatment options for these women.

  • In normal cells, Mismatch Repair (MMR) corrects errors that are introduced during DNA replication via enzymes. Under normal conditions, the enzymes as part of the MMR system restore DNA integrity by detecting and fixing the erroneous strands.[xiv]

  • When this process is defective it is known as Mismatch Repair Deficient (dMMR). dMMR is the result of the enzymes no longer functioning properly, leading to errors in the DNA that go unchecked.[xiv][xv]

  • A dMMR system may result in the accumulation of these errors and may lead to cancer.[xv]

How is endometrial cancer diagnosed?

  • Endometrial cancer is usually diagnosed after a women visits her doctor due to a variety of abnormal symptoms. Pelvic examination, ultrasounds, CT scans, MRIs and endometrial tissue sampling may all be used to diagnose endometrial cancer.[xvi]

Who is at increased risk for endometrial cancer?

  • Certain risk factors can increase the likelihood that a woman will develop endometrial cancer, such as obesity, things that affect hormone levels, age, diet and exercise, type 2 diabetes, family history, past history of breast or ovarian cancer, treatment with radiation therapy to the pelvis[xvii] and past history of endometrial hyperplasia.[xviii]

References

[ii] Cancer Facts & Figures 2021. American Cancer Society. Accessed March 30, 2021. https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2021/cancer-facts-and-figures-2021.pdf 

[iii] Bagaria M, Shields E, Bakkum-Gamez JN. Novel approaches to early detection of endometrial cancer. Curr Opin Obstet Gynecol. 2017;29(1):40-46.

[iv] Burton ER, Sorosky JI. Recognition and Therapeutic Options for Malignancy of the Cervix and Uterus. Obstet Gynecol Clin North Am. 2017;44(2):195-206.

[v] Matteson KA, Robison K, Jacoby VL. Opportunities for Early Detection of Endometrial Cancer in Women With Postmenopausal Bleeding. JAMA Intern Med. 2018;178(9):1222-1223.

[vi] Burke WM, Orr J, Leitao M, et al.  Endometrial Cancer: a review and current management strategies: part II.  Gynecol Oncol. 2014;134(2):393-402.

[vii] Brooks RA, Flemming GF, Lastra RR, et al.  Current recommendations and recent progress in endometrial cancer. CA Cancer J Clin. 2019;69(4):258-279.

[viii] Oaknin A, Tinker AV, Gilbert L, et al. Clinical activity and safety of the anti–programmed death 1 monoclonal antibody dostarlimab for patients with recurrent or advanced mismatch repair–deficient endometrial cancer: a nonrandomized phase 1 clinical trial. JAMA Oncol. 2020;6(11):1766-1772.

[ix] CancerMPact® Patient Metric, Kantar. Available from www.cancermpact.com. Accessed 18 March 2020.

[x] NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Uterine Neoplasms  V1.2020.  © National Comprehensive Cancer Network, Inc. 2020.  All rights reserved.  Accessed April 17, 2020.SGO Clinical Practice Endometrial Cancer Working Group. 

[xi] Le DT, Durham JN Smith KN, et al.  Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade.  Science 2017;357(6349):409-413.

[xii] Lorenzi M, Amonkar M, Zhang J, et al.  Epidemiology of microsatellite instability high (MSI-H) and deficient mismatch repair (dMMR) in solid tumor: a structured literature review.  Journal of Oncology 2020; Article ID 1807929

[xiii] Backes FJ, Haag J, Cosgrove CS, et al.  Mismatch repair deficiency identifies patients with high-intermediate risk (HIR) endometrioid endometrial cancer at the highest risk of recurrence: a prognostic biomarker.  Cancer 2019;125(3):398-405.

[xiv] Microsatellite Instability - Defective DNA Mismatch Repair: ESMO Biomarker Factsheet. Retrieved March 30, 2021, from https://oncologypro.esmo.org/education-library/factsheets-on-biomarkers/microsatellite-instability-defective-dna-mismatch-repair (ESMO p1 [DNA mismatch repair] lines 1-2).

[xv] Mismatch Repair Deficiency – NCI Dictionaries. Retrieved March 30, 2021, from https://www.cancer.gov/publications/dictionaries/cancer-terms/def/mismatch-repair-deficiency

[xvi] American Society of Clinical Oncology. Uterine Cancer: Diagnosis. 6/2017. Accessed March 30, 2021. www.cancer.net/cancer-types/uterine-cancer/diagnosis   

[xvii] American Society of Clinical Oncology. Uterine Cancer: Risk Factors and Prevention. 6/2017. Accessed March 30, 2021. www.cancer.net/cancer-types/uterine-cancer/risk-factors-and-prevention   

[xviii] Endometrial Cancer Risk Factors. American Cancer Society. (n.d.). Accessed April 28, 2021. https://www.cancer.org/cancer/endometrial-cancer/causes-risks-prevention/risk-factors.html.