M. D. Anderson study finds change in HER2 status after treatment with HerceptinSeptember 04, 2008Researchers 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. However, of those women who had residual disease, about one-third had tumors that converted from HER2 positive to HER 2 negative status -possibly indicating a resistance to the targeted therapy. The study will be presented today in advance of the American Society for Clinical Oncology Breast Cancer Symposium. Approximately 30 percent of breast cancer cells have an excess amount of the HER2 protein on their surface, which makes the cancer more aggressive. Herceptin, also known as trastuzumab, is a monoclonal antibody that latches on to these proteins and inhibits tumor growth. It was approved in 1998 for women whose advanced, metastatic breast cancer is HER2-positive; it was approved in 2006 for use in the early setting.
It's known that a small percentage of HER2 positive patients develop a resistance to Herceptin during treatment, and there have been several described mechanisms for Herceptin resistance, said Elizabeth Mittendorf, M.D., assistant professor in M. D. Anderson's Department of Surgical Oncology. "The goal of our study was to determine what percentage of patients who started out HER2 positive convert to HER 2 negative, suggesting that we've possibly identified another mechanism of resistance," said Mittendorf, the study's lead author. "Or we could look at it another way. Maybe the findings determine that in this subset of patients, we've treated their HER2 positive disease. Now, it's the HER2 negative disease that's able to grow." Using the M. D. Anderson Breast Medical Oncology database, the retrospective study identified 143 early stage and locally advanced breast cancer patients, all of whom had tumors expressed HER2 at the time of diagnosis. The women were treated with Herceptin, in combination with taxane- and anthracycline-based chemotherapies, prior to surgery. At the time of surgery, 50 percent of the women achieved a pathologic complete response (pCR), or no evidence of breast cancer. Of those who did not achieve pCR, pre- and post-treatment tissue samples were available for 23 patients The samples were analyzed using FISH, a laboratory technique that uses fluorescent probes to detect specific DNA sequences, in this case, additional copies of the HER2 gene. Seven patients, or 30.4 percent, were found to be HER2 negative at the time of surgery. With a median follow-up of 10.2 months, the researchers also found that two patients (2.8 percent) who had achieved a pCR had recurred, compared to eight patients (11.3 percent) who did not achieve a pCR. Of the second group, tumor samples were available for five; three had converted to Herceptin negative status. Despite these findings, at this time, the clinical applications are limited, said Mittendorf, and she strongly cautions that more research is needed before women who have a change of HER2 status not receive their scheduled Herceptin following surgery. "At this stage, I think the findings advocate for reassessing HER2 status at the time of surgery," said Ana Gonzalez-Angulo, M.D., assistant professor in M. D. Anderson's Department of Breast Medical Oncology and the study's senior author. "However, it would be inappropriate for clinicians to conclude from our study that women with a change in HER2 status should not receive their full course of Herceptin therapy. Certainly, the study warrants further investigation of what might be the best adjuvant therapy for this sub-set of women and suggests that a clinical trial in the adjuvant setting would be appropriate." In the lab, the researchers plan to see if there are any other changes in these tumors that are consistent with what we know about Herceptin resistance, including other mutations, alterations in specific markers. If other tumor markers of resistance are found in these patients, explains Mittendorf, then it would support the idea that HER2 status conversion promotes Herceptin resistance. University of Texas M. D. Anderson Cancer Center | |||||||||||||||||||||
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Related Herceptin Current Events and Herceptin News Articles Genetic Engineering & Biotechnology News reports on growing role of molecular diagnostics Novel platform technologies and key advances in genomics are rapidly driving the development of molecular diagnostics, reports Genetic Engineering and Biotechnology News (GEN). Breast cancer treatment resistance linked to signaling pathway Activation of the Src signaling pathway may cause resistance to standard medical treatment in some patients with breast cancer, and inhibition of this pathway holds the potential to overcome that resistance, according to data presented here at the American Association for Cancer Research Molecular Diagnostics in Cancer Therapeutic Development meeting. 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. First step towards switching off breast cancer and leukaemia Australian scientists have identified a way to 'switch off' a molecule, a key player in the molecular processes that trigger breast cancer and certain forms of leukaemia. OHSU Cancer Instutute researchers find abnormalities in gene for melanoma New research from the Oregon Health & Science University Cancer Institute about mutations in melanoma may bring a wellspring of hope to many patients. Fruit fly protein acts as decoy to capture tumor growth factors, find Penn researchers Researchers at the University of Pennsylvania School of Medicine have shown how Argos, a fruit fly protein, acts as a decoy' receptor, binding growth factors that promote the progression of cancer. Herceptin and chemo improves response rates without major adverse effects in HER2 breast cancer Women with a particularly aggressive form of breast cancer seem to do better if they are treated with a combined anthracycline and taxane chemotherapy regimen before surgery, together with trastuzumab (Herceptin) before and after surgery, according to results from the largest multi-centre trial to investigate this treatment. Double binding sites on tumor target may provide future combination therapy Researchers from the University of Pennsylvania School of Medicine and colleagues at Merck Serono Research in Germany have found that two drugs bind to receptor sites on some tumors in different places at the same time, suggesting the possibility of a new combination therapy for certain types of cancer. New study of targeted therapies for breast cancer -- model for global clinical trials Two targeted medications designed to treat an aggressive form of breast cancer are being tested in a new study involving 8,000 participants in 50 countries across six continents -- a clinical trial that investigators hope will provide a new model for global cancer research. New study reveals for first time how BRCA1 mutations cause breast cancer An international team of researchers led by Columbia University Medical Center's Herbert Irving Comprehensive Cancer Center and Sweden's Lund University has, for the first time, revealed how mutations in the BRCA1 gene lead to breast cancer. Findings show that one way BRCA1 mutations cause cancer is by knocking out a powerful tumor suppressor gene known as PTEN. More Herceptin Current Events and Herceptin News Articles |
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