"One of the important conclusions from this study is that even when you correct for stage - that is, look at tumors of the same stage from white women and black women - tumors from the African-American women tend to have features characteristic of more aggressive and rapidly growing cancers," said Peggy Porter, M.D., lead author of the study and an associate member of Fred Hutchinson's Human Biology and Public Health Sciences divisions. "If their tumors tend to grow more quickly, this may help to explain why their cancers are being diagnosed at later stages, which can lead to poorer outcomes," Porter said.
Other studies have reported similar findings, but the Fred Hutchinson analysis, funded by the National Cancer Institute and the Avon Foundation, is the first to examine tumors for a full array of proteins that control how quickly a cancer cell divides. Porter and colleagues found that tumors from African-American women were more likely to contain abnormal amounts of several cell-cycle regulatory proteins compared to tumors from white women. While the researchers do not yet know if these differences affect a woman's survival from cancer, cancers that lose control of these cell-cycle proteins tend to be more aggressive and harder to cure.
For nearly all factors analyzed, the researchers identified race-specific differences among the cancers, and tumors from African-American women almost always exhibited more aggressive characteristics than those from whites. For example, 13 percent of white women had stage III or higher disease, while nearly 20 percent of African-American women had this level of advanced disease. The odds of having a high-grade tumor, an indication of aggressiveness as judged by microscopic examination of the cells, was more than five times higher for black women than for white women.
Multiple studies have identified social, economic and cultural factors that contribute to later-stage diagnosis and poorer survival of breast cancer among African-Americans, but less is understood about differences in tumor biology that factor into this health disparity. The findings from the Fred Hutchinson study lay the groundwork for future studies to identify the specific risk factors that cause tumors from African-American women to develop dangerous characteristics, which could lead to new strategies to prevent and treat the disease.
"We know that African-American women with breast cancer are diagnosed at later stages, which is undoubtedly due in large part to socioeconomic factors, such as access to medical care. What we don't know is how much tumor biology contributes to diagnosis at later stages," Porter said. "We've just begun to tease out the biological factors that might contribute to late-stage diagnosis."
Study co-author Ralph Coates, Ph.D., associate director for science in the Division of Cancer Prevention and Control at the Centers for Disease Control and Prevention (CDC) in Atlanta, said that the research provides unique new knowledge about the abnormal cell cycle and greater loss of cycle control in breast cancers of African-American women compared with such cancers in white women.
"These new findings can guide further research to identify potentially modifiable risk factors that contribute to the increased risk in African-American women of more aggressive breast cancer," Coates said.
The study involved 124 African-American women and 397 white women aged 20 to 54 who had been diagnosed with breast cancer. The researchers obtained information on each woman's age, race, marital status and the stage of their cancer at diagnosis, which indicates whether the cancer is localized (confined to the breast) or has spread to nearby or distant parts of the body.
Researchers also obtained tissue samples from each woman's tumor, which Porter analyzed for 17 different characteristics that provide information about a tumor's aggressiveness or a patient's prognosis.
Aggressive tumor characteristics more common among African-American women than white women included:
- Estrogen- and progesterone-receptor status (positive or negative): a marker that has been tested and used to assess the likelihood of outcome regarding survival or cancer recurrence. Loss of estrogen and progesterone receptors on tumor cells (such as ER-negative or PR-negative status) is associated with poor clinical outcome. The odds of having ER-negative tumors were nearly three times greater for African-American women than for white women. The odds of having a PR-negative tumor were more than three times greater for African-American women than for white women.
- Mitosis: active cell division as determined by looking at the cancer cells under a microscope. Tumors with a high mitotic count are more aggressive. The odds of having a tumor with a high mitotic count were three times greater for African-American women than for white women.
- P53: a protein product made by the p53 tumor-suppressor gene. When detected in large amounts, it is often associated with abnormal function of p53 and loss of cell-cycle control, which can lead to cancer. The odds of having a tumor with high p53 levels were twice as great for African-American women than for white women.
- Cyclin E: a protein important for proper control of cell division. High levels of cyclin E can cause unrestrained cell division and are associated with poorer survival. The odds of having a tumor with high levels of cyclin E were four times greater for African-American women than for white women.
- Cyclin D: a protein important for proper control of cell division. High levels of cyclin D in many studies are associated with a better chance of survival. The odds of having a tumor with high cyclin D levels were half as great for African-American as for white women.
When researchers reanalyzed these characteristics by comparing tumors from the same stage or from women diagnosed at the same age, many of these aggressive characteristics were still more common among African-American women.
Porter suggested several possible explanations for why tumors from the African-American women exhibit these differences, most of which affect a woman's exposure to the steroid hormones estrogen and progesterone. "One important factor may be differences between the racial groups with respect to reproductive experiences," she said. "The age at which a woman has children and how many children she has could be a factor. Pregnancy results in very high levels of circulating hormones. The question is whether many pregnancies, and therefore extended periods of high hormone levels, at a relatively young age increase the risk for onset of cancer with aggressive characteristics."
Among women aged 45 or younger, African-Americans have a higher risk of developing breast cancer than white women. Yet among older women, whites are more likely than African-Americans to develop breast cancer.
Porter said that one aspect not addressed in this study was whether the aggressive tumor biology they identified in African-American women contributes to poorer survival. Analyses in this group of Atlanta women are under way to determine the relationship of tumor characteristics and survival. Additionally, she and colleagues in the Southwest Oncology Group, a nationwide network of researchers that conducts clinical trials, are beginning a study to address this. Porter will examine many of the cell-cycle-related tumor characteristics analyzed in this study and the survival outcome of black and white breast-cancer patients enrolled in a clinical trial.
"A major benefit of focusing on women in a clinical trial is that we know that all of them received similar treatment," Porter said. "That will enable us to more directly evaluate the correlation between tumor characteristics and survival."
Fred Hutchinson Cancer Research Center, home of two Nobel laureates, is an independent, nonprofit research institution dedicated to the development and advancement of biomedical technology to eliminate cancer and other potentially fatal diseases. Fred Hutchinson receives more funding from the National Institutes of Health than any other independent U.S. research center. Recognized internationally for its pioneering work in bone-marrow transplantation, the center's four scientific divisions collaborate to form a unique environment for conducting basic and applied science. Fred Hutchinson, in collaboration with its clinical and research partners, the University of Washington Academic Medical Center and Children's Hospital and Regional Medical Center, is the only National Cancer Institute-designated comprehensive cancer center in the Pacific Northwest and is one of 38 nationwide. For more information, visit the center's Web site at www.fhcrc.org.
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