Breast cancers more aggressive in African-American women
A study of more than 2,200 women at the Kimmel Cancer Center at Jefferson in Philadelphia shows that African American women have more advanced breast cancer at the time of diagnosis than Caucasian women. In addition, African American women tend to have breast cancer tumor types that are more aggressive and have poorer prognoses.
The findings, the researchers say, are in line with other recent studies and provide more powerful evidence of the continuing need for early breast cancer screening for African American women and the development of individual treatment strategies.
The research was led by Edith P. Mitchell, M.D., clinical professor of medicine and medical oncology at Jefferson Medical College of Thomas Jefferson University and Gloria Morris, M.D., Ph.D., assistant professor of medical oncology at Jefferson Medical College. They compared clinical, molecular and demographic data from 2,230 African American and Caucasian women diagnosed with breast cancer at Thomas Jefferson University Hospital between 1995 and 2002 with similar data on slightly more than 197,000 women in the National Cancer Institute's Surveillance, Epidemiology and End Results database.
Reporting online July 9, 2007 in the journal CANCER, Drs. Mitchell and Morris and their co-workers found that in both databases, African Americans are more likely to have later stage and higher grade tumors at diagnosis, meaning more aggressive and invasive disease, than their Caucasian counterparts. In addition, the breast cancer tumors from African American women had characteristics that predicted worse prognoses and poorer outcomes.
When all stages of breast cancer in the Jefferson patients were analyzed, the results showed that African American women had tumors that were more often estrogen-receptor negative (48 percent versus 37 percent), had higher rates of expression of the growth-promoting gene Ki-67 and higher expression of a tumor inhibiting gene, p53. A more aggressive type of tumor, called the "triple negative," was found in 21 percent of African American women versus 10 percent of Caucasians.
"We know that there is high cell turnover and propensity for p53, a tumor suppressor gene, to be abnormal, in addition to these 'triple negative' features in the African American tumors, making them more aggressive and more likely to metastasize," Dr. Morris says. "These are preliminary data that enable us to plan how we want to pursue further gene studies."
The triple negative status of a tumor is particularly important, affecting the use of well known cancer drugs, notes Dr. Mitchell, who is also associate director of diversity programs at the Kimmel Cancer Center at Jefferson. Such tumors lack estrogen and progesterone receptors, resulting in a lack of effectiveness of the commonly used breast cancer drug tamoxifen. The tumors also lack the HER2-neu receptor protein, rendering the drug Herceptin ineffective as well.
While African American women have been found to have a lower incidence of breast cancer than Caucasian women, African American women die from the disease at a higher rate. The gap between death rates among African American and Caucasian women is increasing. Though access to healthcare is a strong factor contributing to disparities in cancer rates and outcomes between African Americans and Caucasians, says Dr. Mitchell, the Jefferson study and others have shown that biological differences play important roles.
"Our goal is to develop individualized treatment strategies for women with breast cancer and to also increase awareness, particularly in women in populations with poor access to health care and who are at risk for aggressive breast cancers," says Dr. Morris. "In the future, we would like to be able to intervene in a more specific way with a more targeted therapy to reduce the risk of the cancer returning, and improve survival."
"We would like to explore future research that will enhance our knowledge and allow better understanding of these biological differences, and devise better treatment plans that could potentially be effective," says Dr. Mitchell.
Because the findings are similar to those in the federal database, says Dr. Morris, "This meant that they were representative nationally and that we could use this registry for future questions and it would reflect national trends."
They also provide some direction for therapy, Dr. Morris says, enabling physicians to better plan specific treatments for particular breast tumor types. "We want to be able to answer the question, is there something that is going to work better in this more aggressive tumor type."
The overall goal, she notes, is to find new therapeutic targets. To that end, Drs. Morris, Mitchell and their colleagues want to use microarray technology to examine the more aggressive tumor types in African American women and compare them to tumors in Caucasian women to try to sort out differences at the molecular level.