Photo by Todd McNaught
A new study may help to explain why African-American women with breast cancer are more likely to be diagnosed with advanced disease and are less likely to survive the disease than their white counterparts.
In the largest-ever study of its kind, researchers in the Human Biology and Public Health Sciences divisions and collaborators in Atlanta have found that breast tumors from black women are more likely to be fast-growing and aggressive than those from whites. The findings, published in the June 15 issue of Cancer, hold true even for breast tumors of equally advanced stages in the two groups of women.
"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 Dr. Peggy Porter, lead author of the study. "If their tumors tend to grow more quickly, this may help to explain their cancers being diagnosed at later stages, which can lead to poorer outcomes."
Other studies have reported similar findings. But the Fred Hutchinson analysis 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 so-called 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.
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 work 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 present 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."
Dr. Ralph Coates, associate director for science in the Division of Cancer Prevention and Control at the Centers for Disease Control (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 the cancers in white women.
"These new findings can guide further research to identify potentially modifiable risk factors that contribute to the increased the risk in African-American women of more aggressive breast cancer," said Coates, who is also a co-author of the study.
Other investigators who took part in the study were Drs. Ming Gang Lin and Xiaopu Yuan of the PHS and Human Biology divisions, and collaborators at Emory University in Atlanta and the CDC. The study was funded by the National Cancer Institute and the Avon Foundation.
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.
Race-specific tumor differences
For nearly all factors analyzed, the researchers identified race-specific differences among the cancers. 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 greater than five times higher for black women than for white women.
Among the aggressive tumor characteristics more common among African-American women that white women were:
- 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 ER-negative tumors were nearly three times greater for African-American women than 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 often is 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 is associated with poorer survival. The odds of having a tumor with high cyclin E levels was 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 than for white women.
- P16: A cell-division control protein. High levels of p16 can cause unrestrained cell division and have been associated with poorer survival in breast cancer. The odds of having a tumor with high p16 levels were nearly three times greater for African-American women than 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, all of which affect a woman's level of the hormone estrogen. Increased levels of estrogen are a risk factor for breast cancer.
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 to develop breast cancer than African Americans are.
"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 at a young age.
Correlation with survival rates
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. She and colleagues in the Southwest Oncology Group, a nationwide group of researchers that conducts clinical trials, are beginning a study to address this. Porter will examine the same 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 this group of women is that we know that all of them will receive similar treatment," Porter said. "That will enable us to more directly evaluate the correlation between tumor characteristics and survival."
More aggressive growth found in blacks than in whites
Image Provided by Dr. Peggy Porter
Tissue section from a high-grade tumor shows large irregular cells that lack the growth pattern seen in normal breast tissue. According to Dr. Peggy Porter's study, breast tumors from African-American women tend to be of a higher grade than those from white women.