Breast Cancer Mortality Disparities Not Driven By Estrogen Status Alone
Black women who are diagnosed with breast cancer have a higher probability of dying from the disease than white women, regardless of their estrogen receptor status, according to research from the National Cancer Institute (NCI), part of the National Institutes of Health. Differences in breast cancer mortality may reflect racial differences in access and response to innovative breast cancer treatments, as well as other biological and non-biological factors, according to the report. In addition, the researchers found that differences in outcomes in the first few years post-diagnosis make up nearly all of the disparity. These results were published online June 22, 2009 in the Journal of the National Cancer Institute.
Recent years have seen an improvement in overall breast cancer mortality rates, but disparities remain between black and white women, with black women experiencing higher breast cancer mortality rates despite lower incidence rates. Researchers have been studying biological, environmental, and socioeconomic factors, but the underlying cause of this disparity remains unclear.
Black women are more likely than white women to develop breast cancers that lack estrogen receptors — that is, tumors that are estrogen receptor-negative (ER-). These tumors are typically very aggressive and more difficult to treat than estrogen receptor-positive (ER+) tumors, which respond well to tamoxifen. Previously, it has been thought that the difference in the proportion of ER+ to ER- tumors was a major contributor to the gap in mortality rates.
"We were surprised to discover that estrogen-receptor status only accounted for a portion of the disparity," said Idan Menashe, Ph.D., lead author of the study and research fellow in NCI’s Division of Cancer Epidemiology and Genetics (DCEG). "Looking further at the data we were able to pinpoint that disparate outcomes between black and white women, particularly in the first few years following a breast cancer diagnosis, are the driving factor behind this racial gap."
In this study, NCI researchers compared breast cancer rates for black and white women using data from the NCI’s Surveillance, Epidemiology and End Result (SEER) program. They employed statistical techniques to directly evaluate racial disparities in breast cancer outcomes by examining the rate ratios between black and white women for incidence, mortality, and hazard rate (which is roughly the same as the probability of dying), as well as performing sub-comparisons by ER-status. Using ratios of these rates instead of just the simple rates enabled the researchers to compare trends across different subgroups on an equal footing.
They found that, from 1990 to 2004, incidence rate ratios remained fairly stable while the breast cancer mortality rate ratios persistently increased. Furthermore, the researchers observed that, regardless of ER status, black women with breast cancer were still more likely to die of the disease than white women. This disparity remained even when the researchers adjusted for age at diagnosis, stage and grade of the tumor, year of diagnosis, and socioeconomic status. When the researchers examined the hazard rate trends in black and white women, they noticed that the largest differences occurred in the first three years after diagnosis in both ER- and ER+ tumors.
The researchers also examined the incidence-based mortality of breast cancer among black and white women using a novel counterfactual (what if) approach to further explore this disparity. This approach estimates what the mortality outcomes would be if the population was composed differently. In this case, the researchers explored what the black to white mortality rate would have been if the proportion of ER+/- tumors were similar in both the black and white populations, as well as what the mortality rates would have been if the two groups had similar hazard rates.
This analysis confirmed that, despite the higher incidence of ER- tumors (which are associated with a less favorable prognosis) among black women, the differences in survival outcomes between the two populations were driven largely by differences in the hazard rate as opposed to differences in estrogen-receptor status.
"We hope that clinicians and other researchers can use our findings to uncover, address, and eliminate the factors responsible for poorer early outcomes for black women," said Philip S. Rosenberg, Ph.D., senior author on the study and senior investigator in DCEG.
Several factors have been identified as possibly contributing to the increased hazard rates observed among black women, including access to care and response to treatment, health-related racial differences such as obesity, or distribution of tumor sub-types. Adequate insurance coverage, for example, may affect access to the newest therapies, but studies conducted in populations who have equal access to health care have shown that this alone does not account for the widening disparity. The researchers recommend placing a greater emphasis on identification of the driving factors behind the increased hazard rate among black women, and on developing new therapeutic approaches to address the disparity.
Additionally, researchers will need to explore disparities in other ethnic populations, such as Asian and Hispanic women, who have differing rates of breast cancer, and in some instances, more favorable outcomes than black or white women.