From the Journal of the National Cancer Institute

Growth Factors Commonly Given With Chemotherapy
Associated With Increased Risk of Blood Diseases

Andrea Widener
Journal of the National Cancer Institute

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 marrow­which produces blood cells­does
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."