Women with breast cancer who receive compounds that stimulate white blood cell production to help their bodies better tolerate chemotherapy are at an increased risk of developing a type of leukemia or a condition called myelodysplastic syndrome, according to a new study in the February 7 Journal of the National Cancer Institute. The authors note that the absolute risk of the conditions is very small, but that risk should still be taken into consideration when making treatment decisions.
The growth factors granulocyte or granulocyte-macrophage colony-stimulating factor (G-CSF or GM-CSF) have been used to reduce the risk of infections from neutropenia, an abnormally low count of a certain type of white blood cell that helps control infections. Chemotherapy destroys these cells, and it is difficult for the body to quickly replace them.
However, there is some concern that these growth factors may keep cells alive that have been mutated by chemotherapy. Ordinarily, certain cell processes would recognize such damage and instruct the cell to die, but growth factors may save the mutant cell, allowing it to develop into a cancer called acute myelocytic leukemia (AML). There's also concern about the risk of a disease called myelodysplastic syndrome (MDS), in which the bone marrow—which produces blood cells—does not function normally. Indeed, some studies have hinted that cancer patients who receive growth factors with chemotherapy may have an increased risk of these two diseases.
Dawn Hershman, M.D., of the Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center and New York Presbyterian Hospital, and colleagues set out to determine the association between G-CSF or GM-CSF use and the risk of AML or MDS among women treated with chemotherapy for early-stage breast cancer. Using a database that links cancer registry data from the Surveillance, Epidemiology, and End Results (SEER) program with data from Medicare, the researchers identified 5,510 women age 65 and older who were diagnosed with breast cancer and treated with chemotherapy between 1991 and 1999. A total of 906 (16%) were treated with at least one course of G-CSF (832), GM-CSF (29), or both (49). Among these 906 patients, 16 (1.77%) developed AML or MDS; among the 4,604 women who didn't get growth factor treatment, 48 (1.04%) developed one of the diseases. The authors calculated that women who received GM-CSF or G-CSF had twice the risk of developing AML or MDS as women not treated with the growth factors.
"Our study demonstrates that the elevated risk of AML or MDS associated with adjuvant chemotherapy may be further increased by the concurrent use of growth factors," the authors write. "It is unclear if the growth factors cause an increased risk or if the requirements for their use cause an increased risk; however, the absolute overall risk appeared to be small, even among the elderly patients we studied. Nevertheless, if further research confirms this finding, this risk should be factored into clinical decisions with regard to the use of growth factors."
In an editorial, Ivo P. Touw, Ph.D., and Marijke Bontenbal, of the Erasmus University Medical Center Rotterdam in the Netherlands, review the possible biologic mechanisms for the increased risk, and point out that growth factor use has increased in recent years. They also note that the benefits of adjuvant chemotherapy for breast cancer may far outweigh any risk of a second cancer. "In clinical practice, ... the benefits of adjuvant chemotherapy are of a different order of magnitude than the risk of secondary MDS or AML," they write. "Furthermore, given all the unknown factors, associations could be found that have no causal relationship. The evidence for a potential role of G-CSF in the onset of AML/MDS, derived from only a few retrospective studies, thus has to be qualified as hypothesis generating rather than conclusive."