Chandrika Kurpad, MS, LGCG - CGA-IGC Communications Committee
Serous uterine cancer, also known as uterine serous carcinoma (USC), is a rare but aggressive form of endometrial cancer.
Despite comprising only 10% of uterine cancers, it accounts for a disproportionate number of deaths due to its aggressive nature and tendency for late-stage diagnosis [1].
Key Characteristics
Aggressive Behavior: USC grows and spreads quickly, often before symptoms are noticeable [2].
Late-Stage Diagnosis: Many cases are diagnosed at advanced stages, contributing to poor outcomes [2].
Age: USC typically affects older, postmenopausal women, with the average age at diagnosis being in the mid-60s [3].
Symptoms
Common symptoms of USC include:
Postmenopausal bleeding
Abnormal vaginal discharge
Pelvic pain or pressure
Difficulty urinating or changes in bowel habits [4]
It's crucial to note that these symptoms can be caused by various conditions, not just cancer. However, any unusual gynecological symptoms should be evaluated by a healthcare provider promptly.
Genetics and Risk Factors
Recent research has revealed important genetic links in USC:
BRCA1 Mutations: Women with germline BRCA1 mutations have a 2.6% to 4.7% lifetime risk of developing USC, which is 5-10 times higher than the general population [5,6].
TP53 Mutations: Somatic mutations in the TP53 gene are present in up to 90% of USCs, making it a hallmark of this subtype [7].
Lynch Syndrome: While more commonly associated with endometrioid endometrial cancer, Lynch syndrome may also increase the risk of USC [8].
Other risk factors include:
Obesity
Long-term use of tamoxifen for breast cancer treatment
Postmenopausal status [3,4]
Racial Disparities
Serous uterine cancer disproportionately affects women of African American ancestry:
Higher Incidence: African American women have a higher incidence of USC compared to women of other racial/ethnic groups [9].
Mortality Rate: The mortality rate for USC is significantly higher among African American women [10].
Age at Diagnosis: African American women are often diagnosed with USC at a younger age compared to white women [11].
Genetic Factors: Some studies suggest that there may be different genetic risk factors or molecular profiles of USC in African American women, but more research is needed in this area [12].
Access to Care: Disparities in access to healthcare and timely treatment may contribute to poorer outcomes among African American women with USC [13].
Diagnosis and Treatment
Diagnosis of USC typically involves:
Physical exam and medical history
Transvaginal ultrasound
Endometrial biopsy or dilation and curettage (D&C)
Imaging studies (CT, MRI, or PET scans) for staging [4]
Treatment is often multimodal and may include:
Surgery (hysterectomy, removal of ovaries and fallopian tubes, and often lymph node dissection)
Chemotherapy
Radiation therapy
Emerging targeted therapies [14]
Future Directions in Research and Treatment
Ongoing research is focusing on:
Developing more effective targeted therapies
Improving early detection methods
Understanding the molecular mechanisms driving USC to identify new treatment targets
Exploring the role of immunotherapy in treating serous uterine cancer [15]
Investigating the potential of PARP inhibitors, which have shown promise in BRCA-mutated ovarian cancers, for treating BRCA-mutated serous uterine cancers [16]
Understanding and addressing racial disparities in USC incidence and outcomes
Conclusion
Serous uterine cancer is a complex disease with both sporadic and hereditary forms. The recognition of its genetic components, particularly the link to BRCA1 mutations, has opened new avenues for research and personalized treatment approaches. Additionally, the significant racial disparities in USC incidence and outcomes highlight the need for targeted interventions and increased research focus on diverse populations.
As our understanding of the molecular basis of this cancer grows, we hope to see improvements in prevention, early detection, and treatment outcomes for all women diagnosed with this challenging form of uterine cancer, with a particular focus on reducing disparities and improving outcomes for African American women.
References
Bokhman JV. Two pathogenetic types of endometrial carcinoma. Gynecol Oncol. 1983;15(1):10-17.
Fader AN, et al. Uterine papillary serous carcinoma: epidemiology, pathogenesis and management. Curr Opin Obstet Gynecol. 2010;22(1):21-29.
Slomovitz BM, et al. Uterine papillary serous carcinoma (UPSC): a single institution review of 129 cases. Gynecol Oncol. 2003;91(3):463-469.
Hamilton CA, et al. Uterine papillary serous and clear cell carcinomas predict for poorer survival compared to grade 3 endometrioid corpus cancers. Br J Cancer. 2006;94(5):642-646.
Shu CA, et al. Uterine Cancer After Risk-Reducing Salpingo-oophorectomy Without Hysterectomy in Women With BRCA Mutations. JAMA Oncol. 2016;2(11):1434–1440.
de Jonge MM, et al. Linking uterine serous carcinoma to BRCA1/2-associated cancer syndrome: A meta-analysis and case report. Eur J Cancer. 2017;72:215-225.
Zheng W, et al. A proposed model for endometrial serous carcinogenesis. Am J Surg Pathol. 2011;35(1):e1-e14.
Batte BAL, et al. Consequences of universal MSI/IHC in screening endometrial cancer patients for Lynch syndrome. Gynecol Oncol. 2014;134(2):319-325.
Long B, et al. Racial differences in MMR deficiency and PD-L1 expression in uterine serous carcinomas. Gynecol Oncol. 2020;156(3):595-600.
Cote ML, et al. Risk factors for endometrial cancer in black and white women: a pooled analysis from the Epidemiology of Endometrial Cancer Consortium (E2C2). Cancer Causes Control. 2015;26(2):287-296.
Shing DC, et al. Racial disparities in uterine cancer incidence and mortality in the United States: A comprehensive review. JCO Glob Oncol. 2021;7:1456-1467.
Guttery DS, et al. Racial differences in endometrial cancer molecular portraits in The Cancer Genome Atlas. Oncotarget. 2018;9(24):17093-17103.
Collins Y, et al. Inherited and acquired mutations in gynecologic cancers in women of African ancestry. Gynecol Oncol. 2021;162(2):459-468.
Boruta DM 2nd, et al. Management of women with uterine papillary serous cancer: a Society of Gynecologic Oncology (SGO) review. Gynecol Oncol. 2009;115(1):142-153.
Makker V, et al. New therapies for advanced, recurrent, and metastatic endometrial cancers. Gynecol Oncol Res Pract. 2017;4:19.
Konstantinopoulos PA, et al. Homologous Recombination Deficiency: Exploiting the Fundamental Vulnerability of Ovarian Cancer. Cancer Discov. 2015;5(11):1137-54.
Comentários