The authors address an important but extremely broad topic—namely, disparities in cancer care among racial and ethnic minorities[1]—but their emphasis is on breast cancer, which accounts for 61% of the citations (23 of 38),[2] with screening the major focus. The authors outline differences in access, screening, and quality of health care provided to white women compared to women of other ethnicities with breast cancer. While these differences undoubtedly exist, this reviewer believes the authors underemphasize the emerging and established differences in the biology of breast cancers found in African-American women. Such findings may well provide a potential explanation of much of the observed difference in incidence and outcome.
Women's Health Initiative
The issue of racial/ethnic differences in breast cancer was addressed by the Women's Health Initiative, where over 160,000 postmenopausal women in the United States were entered on a series of controlled clinical trials and in an observational cohort. As these studies involved volunteers who would be unlikely to directly benefit from participating, educational and socioeconomic differences across racial/ethnic groups were muted (78% of white and 73% of African-American participants had some schooling after high school, and 96% of white and 94% of African-American participants ever had a mammogram before entry).
Findings were adjusted for a comprehensive range of breast cancer risk factors including mammogram frequency. Compared to white women, African-American women were about half as likely to develop hormone receptor-positive breast cancer.[3] However, the breast cancers diagnosed in African-American women had unfavorable characteristics, with 32% of cancers both high-grade and estrogen receptor-negative (adjusted odds ratio = 4.70, 95% confidence interval = 3.12-7.09, compared to white women)—a putative surrogate for basal-like, triple-negative cancers (estrogen and progesterone(Drug information on progesterone) receptor-negative and HER2-nonoverexpressing).[3] In addition, after adjustment for prognostic factors, mortality after breast cancer was significantly higher in these African-American women compared to white women with the disease.
The results from the Women's Health Initiative analysis were incorporated in a meta-analysis comparing survival after a breast cancer diagnosis in African-American and white patients, and evaluating the relative influence of ethnicity compared to socioeconomic status.[4] This pooled analysis indicated that African-American ethnicity was an independent predictor of poor breast cancer outcome, even after differences in socioeconomic status were included. While comorbidity may contribute to the survival differences seen,[5] strong evidence supports important differences in the underlying cancers as well.
Carolina Breast Cancer Study
The issue of ethnicity and survival in women with breast cancer was recently addressed at the gene expression level in the Carolina Breast Cancer Study.[6] In this study, the prevalence of breast cancer subtypes across ethnicities was examined. A basal-like breast cancer gene expression subtype was more commonly seen among premenopausal African-American women (39%) compared with non-African-American women of any age (16%). These basal-like breast cancers had high mitotic and high histologic grades and would be expected to be diagnosed at a later stage and carry a worse prognosis. In addition, a gradient is seen in the frequency of basal-like breast cancers when comparing native African-Americans in Nigeria (where the frequency of estrogen receptor-negative and HER2-negative breast cancer was highest)[7] vs African-American women in the United States and white US women (where the frequency of such tumors was lowest).[3,6]
Conclusions
Taken together, these findings suggest that a high prevalence of poor-prognosis cancers in African-American women likely plays a substantive role in the poor overall outcome seen in women with the disease. This interpretation is supported by three studies in which African-American and white women had similar breast cancer therapies but clinical outcomes were worse among African-American women.[8-10] Studies to define effective intervention strategies for these poor-prognosis cancers, regardless of racial or ethnic origin of women with such cancers, are urgently needed.
—Rowan T. Chlebowski, MD, PhD
