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Selective marker found to indicate aggressive form of breast cancer
January 15, 2007PHILADELPHIA — 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 patients.
American Association for Cancer Research
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 patients.
American Association for Cancer Research
Breast Cancer News and Current Breast Cancer Events RSSM. D. Anderson study finds change in HER2 status after treatment with Herceptin
Researchers at The University of Texas M. D. Anderson Cancer Center have discovered that when treated with Herceptin prior to surgery, 50 percent of HER2 positive, breast cancer patients showed no signs of disease at the time of surgery.
M. D. Anderson study finds racial disparities in radiation therapy rates for breast cancer
Black women are less likely than white women to receive radiation therapy after a lumpectomy, the standard of care for early stage breast cancer, according to a new study by researchers at The University of Texas M. D. Anderson Cancer Center.
New nano device detects immune system cell signaling
Scientists have detected previously unnoticed chemical signals that individual cells in the immune system use to communicate with each other over short distances.
CSHL scientists identify new drug target against virulent type of breast cancer
Tumor cells in a particular subset of breast cancer patients churn out too much of a protein called ErbB2 -- also often called HER2 -- which drives the cells to proliferate unchecked. Patients unlucky enough to be in this group -- about one in four -- have poorer prognoses and clinical outcomes than those who don't.
Dense tissue promotes aggressive cancers
New research may explain why breast cancer tends to be more aggressive in women with denser breast tissue. Breast cancer cells grown in dense, rigid surroundings step up their invasive activities, Vanderbilt-Ingram Cancer Center investigators report in the Sept. 9 issue of Current Biology.
Women exposed to negative life events at greater risk of breast cancer: BGU study
Happiness and optimism may play a role against breast cancer while adverse life events can increase the risk of developing the disease.
Hormone replacement therapy improves sleep, sexuality and joint pain in older women
One of the world's longest and largest trials of hormone replacement therapy (HRT) has found that post-menopausal women on HRT gain significant improvements in quality of life.
Positive thinking may protect against breast cancer
Feelings of happiness and optimism play a positive role against breast cancer. Research published today in the open access journal BMC Cancer suggests that while staying positive has a protective role, adverse life events such as the loss of a parent or close relative, divorce or the loss of a spouse can increase a woman's risk of developing the disease.
Anti-tumor effects are enhanced by inhibiting 2 pathways rather than 1
Two independent research groups have found that simultaneous inhibition of two signaling pathways resulted in substantially enhanced antitumor effects in mouse models of prostate and breast cancer. In an accompany commentary, Steven Grant, at Virginia Commonwealth University Health Science Center, Richmond, discusses the clinical importance of these studies and highlights some of the questions that still need to be answered.
Why a common treatment for prostate cancer ultimately fails
Some of the drugs given to many men during their fight against prostate cancer can actually spur some cancer cells to grow, researchers have found. The findings were published online this week in a pair of papers in the Proceedings of the National Academy of Sciences.
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