Cancer Research News
Selective Marker Found to Indicate Aggressive Form of Breast Cancer
PHILADELPHIA (January 15, 2007) − Researchers have linked a
structural protein called nestin to a particularly deadly form of breast
cancer, identifying a new biomarker that could lead to earlier detection
and better treatment.
In the January 15 issue of Cancer Research, researchers from Dartmouth
Medical School demonstrate that nestin could represent a selective
biological marker for basal epithelial breast tumors, a highly
aggressive cancer with similarities to mammary stem cells, the
regenerative cells believed to be the site of breast cancer initiation.
“Patients with this type of breast cancer are at high risk for
recurrence,” said James DiRenzo, Ph.D., assistant professor at Dartmouth
Medical School. “Ideally, a marker like nestin would enable clinicians
to monitor these patients through frequent tests of a biomarker and, in
doing so, detect the cancer before it has a chance to come back.”
Basal epithelial tumors lack important molecular targets such as the
estrogen receptor, progesterone receptor and Her2. This not only makes
positive diagnosis difficult, say researchers, but also eliminates
several important lines of therapy, such as tamoxifen or Herceptin, that
work well for other breast cancer subtypes.
“Currently, there is no direct means of determining if a breast cancer
is a basal epithelial tumor – doctors only know for certain once the
other forms of breast cancer are ruled out,” DiRenzo said. “This type of
breast cancer is generally difficult to manage, but several important
studies have shown that it is more likely than other breast cancer
subtypes to respond to certain types of therapy, which highlights the
need for a definitive diagnostic marker.”
The basal epithelial breast cancer subtype represents 17 to 37 percent
of all breast cancers and is more common in premenopausal African
American women than in other demographic groups. Among breast cancers,
this subtype is known to have an early age of onset and a very short
time between treatment and relapse. It is more commonly detected during
normal screening mammogram intervals than other screening subtypes,
which likely reflects its aggressive nature. These important clinical
correlations likely explain why this subtype disproportionately accounts
for breast cancer mortality, according to DiRenzo.
In a retrospective study of breast cancer tumors lacking estrogen
receptors, progesterone receptors and Her2, DiRenzo and his colleagues
found extremely high amounts of nestin in 14 of 16 tumor samples
examined. While the researchers plan to strengthen their findings with a
larger prospective study, their results offer a crucial first step in
diagnosis and management of a disease that is notoriously difficult to
control. Consistent with other studies showing that breast cancers
associated with inherited mutations in BRCA1 display the basal
phenotype, DiRenzo and colleagues found high levels of nestin in these
tumors as well.
Nestin is a long filamentous protein found in adult stem cells in the
central nervous system. While scientists do not know its exact function,
the protein is thought to have a role in stabilizing the structure of
adult stem cells as they regenerate and divide into daughter cells.
“Normal basal epithelial tissue produces nestin, but basal epithelial
tumors produce a tremendous amount of nestin, which likely represents an
abnormal expansion of the basal epithelia.” DiRenzo said. “If it is
indeed specific to regenerative cells, then it will make for an
excellent diagnostic tool for a cancer of regenerative mammary cells.”
According to the DiRenzo, another important next step will be finding an
efficient means of detecting nestin in a clinical screening setting.
While it seems unlikely that a blood test would be sufficient, DiRenzo
believes that a non-invasive test that collects samples from mammary
ducts may enable the development of a screening tool for at-risk
The study was funded by the National Cancer
Institute, the U.S. Department of Defense Breast Cancer Research Program
and the Mary Kay Ash Charitable Foundation.
Source: American Association for Cancer Research