African-American women with breast cancer were more likely to have larger, later-stage tumors that were more difficult to treat and also had lower survival rates than Hispanic and Caucasian women who received the same treatment in two independent series of clinical trials examined by researchers from The University of Texas M. D. Anderson Cancer Center.

The analysis published on line Oct. 23 by Cancer, a peer-reviewed journal of the American Cancer Society, indicates that race is associated with unfavorable tumor biology, which, along with other factors, likely contributes to the lower rate of breast cancer survival among African-Americans.

“These findings should prompt additional research on how we can improve outcomes for African-American patients by understanding and addressing tumor biology,” says first author Wendy Woodward, M.D., Ph.D., assistant professor of radiation oncology at M. D. Anderson. “It’s important to identify unique features in different populations and subgroups of all women with breast cancer so we can understand a woman’s risk and factors that affect her care on an individual level.”

African-American women are less likely than Caucasian women to have breast cancer but are more likely to die from it. Many factors have been implicated in this disparity, the researchers note, including access to health care and screening, differing treatments, socioeconomic status and racial bias.

By examining two series of clinical trials in which treatment was specified and rigorously followed for all patients, the research team minimized biases related to access to care and type of treatment, two variables that often confound analysis of the issue.

Between 1975 and 2000, 2,140 breast cancer patients were treated in two prospective series of clinical trials at M. D. Anderson involving use of the chemotherapy doxorubicin before and after a radical or modified radical mastectomy.

Of the total patients, 1,590 were Caucasian, 300 were Hispanic, and 250 were African-American, with racial categories based on self-reporting by the patients. In both trials, African-American women received at least as many cycles of chemotherapy as did Hispanics and Caucasians.

In the clinical trial for post-operative chemotherapy, the 10-year overall survival rate for African-Americans was 52 percent. For Hispanics and Caucasians it was 62 percent.

More African-American women came to the trial with later stage disease (24 percent compared with 18 percent of Hispanics and 16 percent of Caucasians) and tumors greater than 5 centimeters (22 percent compared with 13 percent each for Hispanic and Caucasians). African-Americans were more likely to have tumors that were estrogen-receptor negative, which are considered more difficult to treat (41 percent compared with 32 percent for Hispanics and 33 percent for Caucasians).

The trial of pre-operative chemotherapy showed similar results, with African-American 10-year survival rate of 40 percent, compared with 56 percent for Hispanics and 54 percent for Caucasians. As in the post-operative trial, higher percentages of African-Americans came to the trial with later-stage disease, larger tumors, and estrogen-receptor negative disease.

A multivariable analysis that took into account age, estrogen receptor-negative status, primary tumor size, and whether the disease had spread to the lymph nodes, showed that African-American race is an independent factor in reduced overall survival rate.

The researchers note they could not take into account factors that might have influenced the patients’ care before they entered the clinical trials. And their analysis did not include socioeconomic factors because that information was not available for patients. However, they doubt socioeconomic factors could fully explain differences in survival rate because Hispanic and African-American women have similar socioeconomic status in M. D. Anderson’s patient referral area.

“We interpret these data as suggesting that intrinsic biological differences in the disease and response to treatment among racial groups contributed to the poorer overall survival rates seen in the African-American cohorts,” the researchers conclude.

“It’s important to note that African-Americans, and people in all self-reported racial groups, are genetically and culturally diverse,” Woodward says. “Not all African-American women will have worse survival prospects for breast cancer, but there are probably subsets of patients for whom we could be doing something better.

“The tools and technology are emerging that will allow us to understand how one person’s tumors differ from another and how we can more effectively assign people to treatments,” Woodward says.

The paper notes that explaining the association of African-American race with more aggressive breast cancer will be challenging, and suggests analysis of genetic variation and regulation of genes by environmental factors as two potential areas of research.