Breast Tumors More Aggressive in African-American Women
by Judith Groch
The poorer breast cancer survival rates for African-American women can be attributed to unfavorable tumor cell biology, not just socioeconomic factors, researchers here reported.
African-American women were more likely to have estrogen-receptor-negative disease and high-grade tumors, and to be diagnosed with more advanced disease, Wendy Woodward, M.D., Ph.D., of the University of Texas M.D. Anderson Cancer Center here, and colleagues, reported online in the Dec.1 issue of Cancer.
These conclusions were derived from a review of 2,140 patients with locally advanced, nonmetastatic breast cancer treated from 1975 to 2000 in two sequential prospective clinical trials at M.D. Anderson.
The retrospective record review of these two independent trials made it possible to control for access bias, the investigators said. The patients were treated with Adriamycin (doxorubicin)-based adjuvant or neoadjuvant therapy, with or without tamoxifen, and mastectomy.
The adjuvant chemotherapy cohort included 1,456 patients: 1,142 Caucasian, 186 Hispanic, and 128 African-American women.
The smaller neoadjuvant chemotherapy cohort included 684 patients: 448 Caucasian, 114 Hispanic, and 122 African-American patients.
In both groups, African-American patients had larger and later-stage tumors (IIIA) (adjuvant P=0.017; neoadjuvant P=0.051) and a higher rate of estrogen receptor-negative disease (adjuvant P=0.054; neoadjuvant P=0.039).
In line with epidemiology studies, which have shown lower overall survival for African-American breast cancer patients, the 10-year actuarial overall survival rate for African-American patients in this study was worse than the rates for the Caucasian or Hispanic patients. In the adjuvant group, the rates were 52%, 62%, and 62%, respectively (P=0.009). In the neoadjuvant group, the rates were 40%, 50%, and 56%, respectively, (P=0.015).
In multivariate analyses to control for confounding factors, the researchers reported that African-American race remained independently associated with an almost 40% poorer overall survival rate in both treatment group: 39% in the adjuvant group (hazard ratio=1.39, P=0.018) and 37% in the neoadjuvant group (hazard ratio=1.37, P=0.02).
In the adjuvant chemo group, 24% of the African-American women were diagnosed with stage III or supraclavicular nodal disease, compared with 16% of the Caucasian patients. Of the African-American women, 22% had tumors larger than 5 cm compared with 13% of the Caucasian women. In the neoadjuvant group, the findings were similar.
These patients had more advanced clinical-stage disease, larger primary tumors, and higher rates of estrogen receptor-negative disease, the researchers wrote.
In neither cohort was there a statistically significant difference in age at diagnosis between the African-American and the Caucasian women. Median age in the adjuvant cohort was 50 (range 15 to 79), while the median age in the neoadjuvant group was similar.
African-American patients received as many chemotherapy cycles as other women in the studies, making it highly unlikely that noncompliance with treatment led to poorer survival rates.
In addition, the researchers said that in the greater Houston area where these studies were conducted, Hispanic and African-American women have similar socioeconomic status. Thus the Hispanic patients, whose survival rates were much better, served as an important comparison group for the African-American patients.
For these reasons, Dr. Woodward said, they have interpreted the data as suggesting that intrinsic biologic differences in the disease and response to treatment among the racial groups contributed to the poorer survival rates for the African-American patients.
It is clear, Dr. Woodward wrote, that because those who report themselves as African American or black represent a genetically and culturally diverse group, explaining how race is associated with biologically aggressive breast cancer will be difficult.
One avenue for future research would be to study whether some African-American women have genetic polymorphisms involved in estrogen regulation. It is also possible that epigenetic phenomena, such as an increased likelihood of being exposed to a carcinogen, might contribute to the formation of more virulent breast cancer.
It is also possible, the researchers suggested, that in an era of targeted therapy, it is not inherent baseline differences in biology that drive the outcomes, but rather imbalances in the biological factors that determine response to new therapy and to which newer therapies are targeted. The findings of this study, they said, suggest that additional work aimed at explaining these mechanisms is warranted.
Discussing the study's limitations, the researchers noted that national statistics show that poorer survival rates among African American patients are also in part due to socioeconomic variables, including less frequent screening, less aggressive treatment, and failure to seek medical care.
In addition, they wrote "African-American patients had more advanced disease at the time of treatment. We were not able to determine whether this was due to less access to healthcare, neglect in seeking healthcare, or intrinsic differences in tumor biology."
However, they said, because this study included only patients treated in clinical trials, some of these potentially confounding variables were minimized. Although the role of socioeconomic factors was not studied directly, the investigators said it was unlikely that it would completely explain the overall poorer survival rate in the study.
Tumor grade, with its well-recognized association with outcome, was not included in the multivariate analysis due to missing data, they said.
And lastly, they said, database demographics indicate that a greater proportion of African American women are less than age 50 at the time of diagnosis compared with Caucasian women. The fact that age did not differ in this study may demonstrate variation between the demographics of this study and the general U.S. population.
Summing up, Dr. Woodward's team wrote that there have been significant efforts over the past decade to increase breast cancer awareness and screening. However, the investigators said, it is equally important to determine whether differences in tumor biology between races also contribute to the noted disparity in outcome.
Ideally, they said, these differences would be best studied in randomized clinical trials that prospectively stratify patients according to socioeconomic factors that may also affect cancer outcome.
