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Sponsored by: |
James Graham Brown Cancer Center |
Information provided by: | James Graham Brown Cancer Center |
ClinicalTrials.gov Identifier: | NCT00375804 |
The objectives for this study:
Condition |
Endometrial Cancer |
MedlinePlus related topics: | Cancer |
Study Type: | Observational |
Study Design: | Cohort, Other |
Official Title: | Racial Disparity in Prevalence and Survival Rates in Endometrial Cancer |
Estimated Enrollment: | 300 |
Study Start Date: | June 2003 |
Estimated Study Completion Date: | May 2009 |
Endometrial cancer is the fourth most common cancer among women and the most common gynecologic cancer. Although the incidence of well-differentiated early stage endometrial cancer is higher among white women, there appears to be an increased incidence of aggressive variants with increased mortality rate among blacks.
Reported 5-year survival rate for white women with endometrial cancer is 90% while black women have only 60% survival. (1,2) Black women tend to have more aggressive cancers and more adverse symptoms such as non-endometrioid histology, grade 3 differentiation, and more stage III and IV cancers. (3,7) Many studies have identified and established risk factors and beneficial behaviors for endometrial cancer, most of which are modifiable. Some of the major risks include obesity, hypertension, high fat diet, diabetes, smoking, increased age, hormone replacement therapy, and tamoxifen use. Behaviors associated with decreased risks are use of oral contraceptives, breast feeding, and physical activity. (4)
There is also evidence that biologic factors may contribute to development of malignant endometrial neoplasms. Both mutation and over expression of the p53 tumor suppressor gene is seen in patients with endometrial cancer, especially those in the advanced stages.
Normally, increased levels of p53 are present in cells with damaged DNA. p53 triggers cells to produce more p21, a molecule that binds to cyclin-dependent kinase 2 (Cdk2). In the unbound state, Cdk2 allows cells to progress to the synthesis stage of the cell cycle; therefore, it remains arrested the Gı phase when it is coupled to p21 in an effort to prevent proliferation of abnormal cells. In addition to this mechanism, p53 is thought to be involved in induction of apoptosis. There are indications that black women may exhibit increased incidence of p53 over expression when compared to white women. (5,6,8)
Another biologic factor involved in endometrial cancer is the estrogen receptor. In contrast to p53, presence of estrogen receptors are a positive prognostic factor because they provide a potential avenue for treating endometrial carcinomas. However, the receptors must be functional in order to be advantageous. Some tumors contain mutated estrogen receptors, which cause changes in the metabolic pathway. Individuals with mutated receptors have varying susceptibilities to developing endometrial cancer. (9)
Aromatase is an enzyme involved in converting androgens to estrogens. Both estrogen and aromatase excess has been identified in endometrial cancer, while no aromatase activity has been indicated in the normal endometrium. Most of the aromatase activity appears to be confined to the stromal cells and is correlated with stromal invasion. It may be possible to inhibit aromatase in an effort to decrease estrogen levels and potentially halt cancer growth. (10,11)
Uterine papillary serous carcinoma (UPSC) is an aggressive variant of endometrial cancer characterized by early metastasis, resistance to therapy, and a high mortality rate. Smaller studies suggest that HER-2/neu may be involved in the tumorigenesis of this disease.(13) Overexpression of the HER2/neu receptor in UPSC is an independent variable that is associated with a poorer overall survival, a worse overall prognosis, occurs more frequently in black women, and may contribute to racial disparity in survival. (12,13)
Genders Eligible for Study: | Female |
Accepts Healthy Volunteers: | No |
Sampling Method: | Probability Sample |
Chart review of subjects diagnosed with endometrial cancer
Inclusion Criteria:
Exclusion Criteria:
Contact: Lynn P. Parker, MD | 502 561-7220 |
United States, Kentucky | |||||
James Graham Brown Cancer Center | Recruiting | ||||
Louisville, Kentucky, United States, 40202 | |||||
Contact: Lynn P. Parker, MD 502-561-7220 | |||||
Principal Investigator: Lynn P. Parker, MD |
James Graham Brown Cancer Center |
Principal Investigator: | Lynn P. Parker, MD | University of Louisville, James Graham Brown Cancer Center |
1. Miller BA, et al. Racial/Ethnic patterns of cancer in the United States 1988-1992, National Cancer Institute, NIH Pub. No. 96-4104. Bethesda, MD, 1996.
2. Miller BA, et al. Cancer Statistics, review: 1973-1989. National Cancer Institute Publication No. (NIH) 92-2789, 1992.
3. Liu JR, et al. Relationship between race and interval to treatment in endometrial cancer. Obstetrics and Gynecology 1995 Oct: 86(4Pt1: 486-90.
4. www.cancer.gov/cancerinfo
5. Kohler MF, et al. Gynecology: p53 overexpression in advanced-stage endometrial adenocarcinoma. American Journal of Obstetrics and Gynecology, Volume 175(5). November 1996. 1246-1252.
6. Clifford SL, et al. Racial disparity in overexpression of the p53 tumor suppressor gene in stage I endometrial cancer. American Journal of Obstetrics and Gynecology, Volume 176 (6). June 1997. 229S-232S.
7. Connell PP, et al. Race and clinical outcome in endometrial carcinoma. Obstetrics and Gynecology, Volume 94(5). November 1999. 713-720
8. Mendelsohn J, et al. The Molecular Basis of Cancer. 2nd edition. W.B.Saunders Co. Philadelphia, 2001.
9. Sasaki M, et al. Polymorphisms of estrogen receptor alpha gene in endometrial cancer. Biochemical and Biophysicial Research Communications. Volume 297(3). 27 September 2002. 558-564
10. Sasano H and Harada N. Intratumoral aromatase in human breast, endometrial and ovarian malignancies. Endocrine Reviews 19(5). 1998. 593-607
11. Elit, et al. Current status and future innovations of hormonal agents, chemotherapy, and investigational agents in endometrial cancer. Current opinion in Obstetrics and Gynecology. Volume 14(1). February 2002. 67.73
12. Santin AD,et al. Racial differences in the overexpression of epidermal growth
factor type II receptor (HER2/neu): a major prognostic indicator in uterine serous
papiollary cancer. Am J Obstet Gynecol. 2005 Mar: 192 (3): 813-8.
13. Slomovitz BM, et al. HER-2/neu overexpression and amplification in uterine
papillary serous carcinoma. J Clin Oncol. 2004 Aug1; 22 15): 3126-32
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Responsible Party: | James Graham Brown Cancer Center ( Lynn P. Parker, MD ) |
Study ID Numbers: | 357.03 |
First Received: | September 11, 2006 |
Last Updated: | May 5, 2008 |
ClinicalTrials.gov Identifier: | NCT00375804 |
Health Authority: | United States: Institutional Review Board |
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