Poorer outcomes for African American women with estrogen-receptor positive (ER+) breast cancer, compared with European American patients, appears to be due, in part, to a strong survival mechanism within the cancer cells. These study results were presented at the American Association for Cancer Research (AACR) Annual Meeting 2015, in Philadelphia, Pennsylvania.
Investigators reported that breast tumors from African American patients show reduced sensitivity to tamoxifen, a leading treatment for ER+ breast cancer, caused by increased activation of the unfolded protein response (UPR).
If UPR is activated due to stress within a cancer cell from anticancer treatment, “it can switch on a prosurvival pathway, allowing tumor cells to hunker down and wait out the attack,” said the study’s lead investigator, Ayesha Shajahan-Haq, PhD, an oncology research assistant professor at Georgetown Lombardi Comprehensive Cancer Center in Washington, DC.
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“From our gene analyses, we found increased activation of the UPR prosurvival pathway in African American patients, compared with other patients, along with increased activity of a number of genes associated with that pathway,” said Shajahan-Haq. “This can lead to increased resistance to common therapies.”
About 70% of all breast cancers are ER+, which means they depend on estrogen to grow. In many of these cancers, treatment involves preventing estrogen from reaching the cancer cell. However, approximately 50% of treated tumors develop treatment resistance. African American women with this breast cancer subtype, treated the same way as European American women, have worse progression-free and overall survival, for reasons that have not been understood.
“Our findings offer a partial understanding of racial differences within ER+ breast cancers,” Shajahan-Haq said. “We demonstrate both increased resistance to anticancer therapy in African American patients as well as the reason that resistance occurs.”
“Biology may not be the only factor contributing to the racial disparities in outcome in the general public,” add Shajahan-Haq. “Factors such as access to mammography, follow-up care or treatment, income status, and other social factors have also been shown to contribute to disparities in outcome.”
Still, in terms of treatment, strategies that target this critical prosurvival UPR pathway could reduce treatment resistance, offering more effective therapy for African American women with ER+ breast cancer, Shajahan-Haq said.
