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

Georgetown Lombardi Comprehensive Cancer Center investigators report 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," or UPR. If UPR is activated due to stress within a cancer cell from anti-cancer treatment, "it can switch on a pro-survival pathway, allowing tumor cells to hunker down and wait out the attack," says the study's lead investigator, Ayesha Shajahan-Haq, PhD, an oncology research assistant professor. "From our gene analyses, we found increased activation of the UPR pro-survival pathway in African-American patients, compared with other patients, along with increased activity of a number of genes associated with that pathway," says Shajahan-Haq. "This can lead to increased resistance to common therapies." About 70% of all breast cancers are ER+, which means that they depend on estrogen to grow. In many of these cancers, treatment involves preventing estrogen from reaching the cancer cell. However, about 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 says. "We demonstrate both increased resistance to anti-cancer therapy in African-American patients as well as the reason that resistance occurs."