Racial differences in the expression of cell cycle-regulatory proteins in breast carcinoma.

African-American (AA) women are more likely to be diagnosed with an advanced stage of breast carcinoma than are white women. After adjustment for disease stage, many studies indicate that tumors in AA women are more likely than tumors in white women are to exhibit a high level of cell proliferation and features of poor prognosis. The purpose of the current study was to compare tumor characteristics and cell cycle alterations in AA women and white women that might affect the aggressiveness of breast carcinoma. The study included 124 AA and 397 white women, ages 20-54 years. These women were enrolled in a case-control study in Atlanta, Georgia, between 1990 and 1992. Breast tumor specimens obtained from these women were centrally reviewed for histologic characteristics and evaluated for expression of estrogen and progesterone receptors (ER/PR), c-ErbB-2, Ki-67, p53, cyclin E, cyclin D1, p27, p16, pRb, and p21 by immunohistochemistry. Logistic regression models were used to assess the age- and stage-adjusted associations of various tumor characteristics with race. The odds of a breast carcinoma diagnosis at a younger age and at a later stage were higher for AA women than for white women. After adjustment for disease stage and age at diagnosis, AA women also were found to have increased odds of having a higher-grade tumor, a higher mitotic index, marked tumor necrosis, ductal histology, loss of ER and PR, overexpression of cyclin E, p16, and p53 and low expression of cyclin D1 at diagnosis. The observed differences between tumor specimens obtained from AA women and tumor specimens obtained from white women, independent of stage and age at diagnosis, indicated that race may be a determinant, or a surrogate for other determinants, of aggressive breast carcinoma and specific cell cycle defects.