A new study has reported that anti-anemia treatments based on erythropoietin reduce the effectiveness of Herceptin in treating HER2 overexpressing breast cancer. Erythropoietin controls the body's red blood cell production and is the basis for recombinant human erythropoietin (also known as erythropoietin-stimulating agents or erythropoiesis-stimulating agents) designed to increase red blood cell production. Recombinant human erythropoietin (e.g., epoetin alfa (Procrit), epoetin beta (Mircera), darbepoetin alfa (Aranesp)) is used to treat chemotherapy-related anemia, thereby eliminating the need for a blood transfusion in some patients. Herceptin is a targeted therapy that blocks the cancer-promoting human epidermal growth factor receptor-2 protein. The authors found that the receptor for erythropoietin is expressed along with the receptor for human epidermal growth factor in a significant proportion of breast cancer cell lines and human breast cancer specimens.
When breast cancer cells that were positive for both HER2 and erythropoietin receptors were exposed to recombinant human erythropoietin, the cells' response to Herceptin both in cell culture and in mice with implanted tumors was reduced. The authors also determined how erythropoietin undermines Herceptin's therapeutic effects: erythropoietin can initiate a chain of events that activates a crucial component of a pathway that Herceptin blocks. Erythropoietin also shuts down the tumor-suppressing gene PTEN, a gene is believed to be important to Herceptin's activity against breast cancer cells. However, the authors found no evidence that recombinant erythropoietin alone promotes cancer growth. In an additional retrospective study of 111 breast cancer patients, the authors found that, compared with administration of Herceptin alone, concurrent administration of recombinant human erythropoietin and Herceptin was associated with shorter progression-free and overall survival in patients with HER2-positive metastatic breast cancer. In a separate interview, study senior author Zhen Fan commented that "the whole idea with targeted therapy against the HER2 protein is to shut off the downstream molecular activity launched by HER2. Erythropoietin can activate similar downstream pathways if its receptor is expressed on cancer cells, causing antagonism between the two drugs."
Please see our article on Herceptin for more information on how to optimize treatment with Herceptin.