Selective marker found to indicate aggressive form of breast cancer

January 15, 2007

PHILADELPHIA -- 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.
-end-
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.

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes more than 24,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

American Association for Cancer Research

Related Breast Cancer Articles from Brightsurf:

Oncotarget: IGF2 expression in breast cancer tumors and in breast cancer cells
The Oncotarget authors propose that methylation of DVDMR represents a novel epigenetic biomarker that determines the levels of IGF2 protein expression in breast cancer.

Breast cancer: AI predicts which pre-malignant breast lesions will progress to advanced cancer
New research at Case Western Reserve University in Cleveland, Ohio, could help better determine which patients diagnosed with the pre-malignant breast cancer commonly as stage 0 are likely to progress to invasive breast cancer and therefore might benefit from additional therapy over and above surgery alone.

Partial breast irradiation effective treatment option for low-risk breast cancer
Partial breast irradiation produces similar long-term survival rates and risk for recurrence compared with whole breast irradiation for many women with low-risk, early stage breast cancer, according to new clinical data from a national clinical trial involving researchers from The Ohio State University Comprehensive Cancer Center - Arthur G.

Breast screening linked to 60 per cent lower risk of breast cancer death in first 10 years
Women who take part in breast screening have a significantly greater benefit from treatments than those who are not screened, according to a study of more than 50,000 women.

More clues revealed in link between normal breast changes and invasive breast cancer
A research team, led by investigators from Georgetown Lombardi Comprehensive Cancer Center, details how a natural and dramatic process -- changes in mammary glands to accommodate breastfeeding -- uses a molecular process believed to contribute to survival of pre-malignant breast cells.

Breast tissue tumor suppressor PTEN: A potential Achilles heel for breast cancer cells
A highly collaborative team of researchers at the Medical University of South Carolina and Ohio State University report in Nature Communications that they have identified a novel pathway for connective tissue PTEN in breast cancer cell response to radiotherapy.

Computers equal radiologists in assessing breast density and associated breast cancer risk
Automated breast-density evaluation was just as accurate in predicting women's risk of breast cancer, found and not found by mammography, as subjective evaluation done by radiologists, in a study led by researchers at UC San Francisco and Mayo Clinic.

Blood test can effectively rule out breast cancer, regardless of breast density
A new study published in PLOS ONE demonstrates that Videssa® Breast, a multi-protein biomarker blood test for breast cancer, is unaffected by breast density and can reliably rule out breast cancer in women with both dense and non-dense breast tissue.

Study shows influence of surgeons on likelihood of removal of healthy breast after breast cancer dia
Attending surgeons can have a strong influence on whether a patient undergoes contralateral prophylactic mastectomy after a diagnosis of breast cancer, according to a study published by JAMA Surgery.

Young breast cancer patients undergoing breast conserving surgery see improved prognosis
A new analysis indicates that breast cancer prognoses have improved over time in young women treated with breast conserving surgery.

Read More: Breast Cancer News and Breast Cancer Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.