Trial Information

Racial Disparity in Prevalence and Survival Rates in Endometrial Cancer

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)