Erythropoiesis stimulating agents and clinical outcomes of invasive breast cancer patients receiving cytotoxic chemotherapy

The use of erythropoiesis stimulating agents (ESAs) to treat anemia in breast cancer patients who are treated with chemotherapy is a matter of ongoing debate. Several recent randomized trials challenged conventional wisdom, which holds that ESAs are contraindicated for breast cancer patients undergoing curative treatment. We aimed to perform the first large national population-based study to analyze the association between ESA use and breast cancer patient outcomes. Cytotoxic chemotherapy-treated invasive breast cancer patients were identified from the Surveillance, Epidemiology, and End Results (SEER)-Medicare database. Non-ESA users were sequentially 1:1 matched to 2,000 randomly sampled ESA users on demographics (age, diagnosis year, race, marital status, and socioeconomic status), tumor presentation (stage, grade, and status of hormone receptors), and treatments (surgery, radiation, and sub-types of chemotherapy) using a minimum distant strategy. Breast cancer-specific survival of ESA and matched non-ESA users was compared using Fine and Gray competing risk model. Compared to ESA users, non-ESA users exhibited dramatically different baseline characteristics such as less advanced tumor, and fewer co-morbidities. Non-ESA users had a significantly more favorable breast cancer-specific survival (subdistribution hazard ratio [sHR] = 0.75, p < 0.0001). This survival disparity was progressively diminished in the sequential matching of demographics (sHR = 0.74, p = 0.0004), presentation (sHR = 0.86, p = 0.06), and treatment (sHR = 0.89, p = 0.17) variables. Stratified analyses identified subgroups of patients whose breast cancer-specific survival were not different between ESA and non-ESA users. In the SEER-Medicare database, ESA usage does not seem to be associated with unfavorable breast cancer-specific survival in breast cancer patients receiving cytotoxic chemotherapy. The ESA-breast cancer prognosis association is complex and requires more intensive investigations.