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fascinating presentatio from ASCO--her2 on breast cancer stem cells and bc stem cells
may be wiped out by a year of herceptin, whereas her2 normal breast cancer patients stem cells may be wiped out by herceptin but may take 2-3 years of treatment. THIS is based on a mathematical model, not a clinical trial
AACR: Are Cancer Stem Cells Vulnerable to Trastuzumab?
By Ed Susman, Contributing Writer, MedPage Today
Published: April 19, 2010
Reviewed by Dori F. Zaleznik, MD; Associate Clinical Professor of Medicine, Harvard Medical School, Boston and
Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner
THIS IS based on a mathematical model -- not a clinical trial -- treatment with trastuzumab (Herceptin) in the adjuvant setting could eventually wipe out breast cancer stem cells, even in women whose breast cancer does not overexpress the HER-2 gene.
Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered preliminary until published in a peer-reviewed journal.
WASHINGTON -- Mathematical modeling suggests that even in women whose breast cancer does not overexpress the HER-2 gene, treatment with trastuzumab (Herceptin) in the adjuvant setting could wipe out cancer stem cells, researchers reported here.
"We predict that a year of trastuzumab therapy would likely eradicate breast cancer stem cells in patients in which the tumor overexpressed HER-2," said Mary E. Sehl, MD, PhD, of UCLA, during a poster presentation at the annual meeting of the American Association for Cancer Research.
Sehl added that if trastuzumab were prescribed for patients with tumors that expressed normal levels of HER-2, the treatment would still drive the breast cancer stem cells in that population to extinction -- but it might take three to four years of therapy.
"We have seen that there are subgroups of women with normal HER-2 levels that appear to benefit from trastuzumab therapy," Sehl told MedPage Today, "so our mathematical models indicate that these patients could also eradicate cancer stem cells."
Clinical trials are under way to test that theory now.
Sehl explained that the model includes information gained through earlier work suggesting that a subpopulation of cells in human breast tumors have characteristics of cancer stem cells.
"These breast cancer stem cells have been recently shown to have increased expression of HER-2, suggesting that these breast cancer stem cells might have a chance of being eradicated with therapy targeting HER-2," she said.
Other researchers were intrigued but cautious.
"At the end of the day we really need to see how this mathematical model relates to treatment in people," said Nancy Davidson, MD, director of the University of Pittsburgh Cancer Institute.
Davidson told MedPage Today that scientists have been debating the significance of cancer stem cells and how important they are in disease proliferation.
"However, the finding in this study might help to explain the perplexing clinical question of why some breast cancer patients with normal HER-2 gene expression do benefit from trastuzumab therapy," she said.
In their mathematical model, Sehl and colleagues used a linear birth-death process model to make their predictions.
The model was based on examinations of the effects of varying degrees of HER-2 overexpression and susceptibility of breast cancer stem cells.
"We determined through the model that breast cancer stem cells approach extinction under trastuzumab therapy in reasonable periods of time," Sehl said.
"We predict that even HER-2 negative tumor cells will eventually go extinct and therefore HER-2-targeted therapy should benefit patients in whom the bulk of the tumor does not overexpress HER-2."
The study was supported by grants from the U.S. Public Health Service; the National Institutes of Health; a career development award funded by the American Society of Clinical Oncology and the Breast Cancer Research foundation.
Sehl and her co-authors made no industry disclosures. Davidson had no disclosures.
Primary source: American Association for Cancer Research
Source reference:
Riley L, et al "Breast cancer stem cell extinction models: Implications for HER2 targeted therapy" AACR 2010; Abstract
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