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The Lancet Oncology

Saturday, July 11, 2009

Study Points to Possible Reasons Why African-Americans Fare Worse With Cancer.

Among man and women with sex-specific cancers, including breast, ovarian, and prostate cancer, African Americans have a higher mortality rate than Caucasian. This is the conclusion of an analysis of clinical trial data which implicates biological factors behind worse outcomes for African-Americans.

After analyzing almost 20,000 patient records from the Southwest Oncology Group's (SOG) database of clinical trials finds, the researchers, for the first time, noted potential biological factors as an explanation why African-American patients with sex-specific cancers tend to die earlier than patients of other races. This despite identical medical treatment regimens for all patients involved and enrollment in the same phase III SWOG trials with uniform stage, treatment, and follow-up. Other confounding socioeconomic factors were also controlled.

Breast cancer
In unrelated earlier studies, observed variations in breast cancer survival by racial/ethnic background had been attributed to a number of varying factors, including differences in clinical and pathologic disease features at diagnosis and economic resource inequities that may affect treatment access and quality.

Whether African-American women have biologically more aggressive breast carcinoma compared with women of other races and whether race acts as a significant independent prognostic factor for was a question that for many years remained unanswered. The general consensus was that race could be a surrogate for socioeconomic status (SES). Researchers in often concluded that a mortality deficit for African-American women relative to Caucasian women, was due to greater mortality from noncancer causes among African-Americans. A retrospective literature review in 2002 by Cross et al demonstrated that while socioeconomic factors replaced race as a predictor of worse outcome after women were diagnosed with breast carcinomas, black women generally presented more advanced disease that appeared more aggressive biologically at a younger age compared with white women.

Prostate cancer
Similar racial/ethnic disparities have been observed in prostate cancer rates. Large population-based cross-sectional studies show the highest incidence and mortality rates among African-Americans followed by non-Hispanic Whites, Hispanics, and Asian/Pacific Islanders. In many studies African-Americans men have two- to fivefold increased risk of prostate cancer deaths in comparison to non-Hispanic Whites across all levels of their socioeconomic status (SES). Based on these results, many researchers felt that socioeconomic status alone could account for the greater burden of prostate cancer among African-American men.

Non Sex-specific cancers
Furthermore, various key studies into other major cancers, including non sex-specific cancer such as colon cancer, generally attributed to the disparity in survival in racial/ethnic settings to a number of varying causes, including diagnosis at later disease stage and other unfavorable disease features, inadequate treatment, and socioeconomic factors.

After analyzing the results of the Eastern Cooperative Oncology Group's E3200 trial, Dr Paul Catalano, D.Sc.,of the Harvard School of Public Health and the Dana-Farber Cancer Institute in Boston found that African Americans with metastatic colorectal cancer (MCC) do not fare as well as Caucasians when, in a specific treatment, bevacizumab (Avastin), a targeted vascular endothelial growth factor inhibitor, is added to the FOLFOX regimen.

In analyzing the data accumulated in the trial that included 713 Caucasians and 66 African Americans, Dr. Catalano and colleagues determined that, in the E3200 trial, African Americans had a lower objective response rate - 3% versus 12.5% (P=0.02), a non-significant shorter time of progression-free survival (P=0.08) and a significantly shorter overall survival (10.2 months versus 11.8 months, (P=0.03). They noted that and this difference remained after adjustment for treatment, gender, age and performance status.

Analytical outcome
The SOG analyses for the first time, shows overwhelming evidence pointing to biological or host genetic factors as the potential source of the survival gap between African Americans and Caucasian patients.

Of 19 457 patients registered, 2308 (11.9%, range = 3.9%–21.6%) were African American. After adjustment for prognostic factors, African American race was associated with increased mortality in patients with early-stage premenopausal breast cancer (hazard ratio [HR] for death = 1.41, 95% confidence interval [CI] = 1.10 to 1.82; P = .007), early-stage postmenopausal breast cancer (HR for death = 1.49, 95% CI = 1.28 to 1.73; P < .001), advanced-stage ovarian cancer (HR for death = 1.61, 95% CI = 1.18 to 2.18; P = .002), and advanced-stage prostate cancer (HR for death = 1.21, 95% CI = 1.08 to 1.37; P = .001).

No statistically significant association between race and survival for lung cancer, colon cancer, lymphoma, leukemia, or myeloma was observed. Additional adjustments for socioeconomic status did not substantially change these observations. Ten-year (and median) overall survival rates for African American vs all other patients were 68% (not reached) vs 77% (not reached), respectively, for early-stage, premenopausal breast cancer; 52% (10.2 years) vs 62% (13.5 years) for early-stage, postmenopausal breast cancer; 13% (1.3 years) vs 17% (2.3 years) for advanced ovarian cancer; and 6% (2.2 years) vs 9% (2.7 years) for advanced prostate cancer.

Access to Quality treatment
"When you look at the dialogue about the issue of race and cancer survival that's gone on over the years," says the paper's lead author, Kathy Albain, M.D., a breast and lung cancer specialist at Loyola University's Cardinal Bernardin Cancer Center, "it always seems to come down to general conclusions that African-Americans may in part have poorer access to quality treatment, may be diagnosed in later stages, and may not have the same standard of care delivered as Caucasian patients, leading to a disparity in survival."

The study, published online by the Journal of the National Cancer Institute (JNCI), found that when treatment was uniform and differences in tumor prognostic factors, demographics, and socioeconomic status were controlled, there was in fact no statistically significant difference in survival based on race for a number of other cancers -- lung, colon, lymphoma, leukemia, and multiple myeloma.

"The good news is that for most common cancers," Albain says, "if you get good treatment, your survival is the same regardless of race. But this is not the case for breast, ovarian, and prostate cancers."

Even with good treatment by the same doctors, African-American patients with one of these three cancers faced a significantly higher risk of death than did other patients, ranging from a 21% higher risk for those with prostate cancer to a 61% higher risk for ovarian cancer patients.
The elimination of treatment and socioeconomic factors as the cause of this higher mortality "implicates biology," says study co-author Dawn L. Hershman, M.D., of the Columbia University College of Physicians and Surgeons.

"There may be differences in genetic factors by race that alter the metabolism of chemotherapy drugs or that make cancers more resistant or more aggressive," she adds.

Earlier this year, Hershman, et al published a smaller study that found that, at least with breast cancer, disparities in survival based on race persist even after adjusting for differences in treatment. That study, published in the May 2009 issue of Journal of Clinical Oncology, analyzed data on 634 breast cancer patients.

"Our study of multiple cancers is distinguished from others that have looked at race-based disparities by its size and by the source of its data," says Joseph Unger of the Southwest Oncology Group's Statistical Center, who was statistician and co-author on the new JNCI study.
The study analyzed records from 35 clinical trials - going back as far as 1974 - that had been conducted by the Southwest Oncology Group, an NCI-sponsored cooperative group headquartered at the University of Michigan. Using data from clinical trials, which are already controlled for a range of potentially confounding factors such as differences in diagnosis, treatment, and follow-up, helps throw the remaining factors into sharper relief, according to Frank L. Meyskens, Jr., M.D.

"It's because of the similar way that people are treated on clinical trials that these differences are even detectable," he says. Meyskens is associate chair for Cancer Control and Prevention for the Southwest Oncology Group and director of the University of California-Irvine's Chao Family Comprehensive Cancer Center.

Long term prediction
The urgency of addressing the reasons for racial disparities in outcomes - both sociological and biological - is amplified by another recent study in the Journal of Clinical Oncology. In this study, Benjamin Smith and colleagues predict that cancer incidence among minorities will nearly double in the coming decades, increasing 99% by 2030 compared to an expected 31% increase among whites. Overall, from 2010 to 2030, the percentage of all cancers diagnosed in older adults will increase from 61% to 70%, and the percentage of all cancers diagnosed in minorities will increase from 21% to 28%

Disparities in Cancer Care
In 2008, the American Society of Clinical Oncology (ASCO), the world’s leading professional organization representing physicians who treat people with cancer, published a ‘Disparities in Cancer Care’ policy statement that recommends a set of strategies designed to address the disparities of cancer care experienced by underserved and minority populations.

The recommendations offered by ASCO suggest that strategies should focus on education, prevention, diagnosis, and treatment and should discuss issues regarding the resources and funding routinely available, talk about misconceptions regarding clinical trials and cancer research, address lack of minority representation among oncologists. The authors of the ASCO policy statement feel that addressing these topics, coupled with improved access to care, are likely to yield improved outcomes for minority cancer patients.

"The elimination of socioeconomic and healthcare access disparities must be a priority in the United States," says Lisa Newman, M.D., director of the Breast Care Center at the University of Michigan Comprehensive Cancer Center. "However, Dr. Albain's landmark study demonstrates that further investigation of race- or ethnicity-associated differences in primary tumor biology is also important."

John Crowley, Ph.D., of the Southwest Oncology Group Statistical Center and Charles A. Coltman, M.D., of the University of Texas Health Science Center were also coauthors of the study, which was funded by the National Cancer Institute.

The Southwest Oncology Group is one of the largest cancer clinical trials cooperative groups, with a network of almost 5,000 physician-researchers practicing at more than 500 institutions, including 19 of the National Cancer Institute-designated cancer centers. The Group is headquartered at the University of Michigan in Ann Arbor, Mich. The Group has an operations office in San Antonio, Texas and a statistical center in Seattle, Washington.

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Also read these PubMed Abstracts:

Images courtesy American Society of Clinical oncology (ASCO)

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