Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04626 (erbB-2)
 5,251 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The HER-2/neu oncoprotein is an important cellular target for the development of a variety of targeted therapies for HER-2/neu-positive breast cancer. Methods for tumor analysis such as immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH) are routinely used to determine the HER-2/neu status of patients with breast cancer and their eligibility for HER-2/neu-targeted therapies, such as trastuzumab (Herceptin) and lapatnib (Tykerb). In a January 2008 article in the Wall Street Journal, it was reported that breast cancer patients may be receiving the wrong treatments or no treatment because of errors in the laboratory tests (IHC/FISH) that are widely used to determine the HER-2/neu status of breast cancers. Numerous reports have demonstrated that 20 to 30% of patients with primary breast cancer have HER-2/neu positive tumors. However, several studies have also shown that up to 40% of patients who are designated HER-2/neu negative with primary tumor analysis by IHC/FISH are actually HER-2/neu positive when the corresponding metastatic tumor is also evaluated by IHC/FISH. Studies have also demonstrated that up to 40% of patients with breast cancer who have a HER-2/neu-negative primary tumor as determined by IHC/FISH can develop elevated levels (> 15 ng/ml) of the circulating HER-2/neu oncoprotein during metastasis. Therefore, elevated serum HER-2/neu levels can be used to alert physicians of the possible presence of HER-2/neu-positive breast cancer in patients who have been previously classified as HER-2/neu negative. Collectively, these studies identify a population of women designated HER-2/neu negative that could have HER-2/neu-positive breast cancer, but have not been eligible for targeted therapies such as trastuzumab and lapatinib. Women who are incorrectly classified as HER-2/neu negative, but are also ineligible for approved HER-2/neu-targeted therapies, may also not be considered for clinical trials of additional HER-2/neu therapies in development. Several studies have also demonstrated that serum HER-2/neu can be elevated in patients with early breast cancer, and up to 90% of patients with HER-2/neu-positive metastatic breast cancer can have elevated serum HER-2/neu levels. These studies have also revealed that the frequency of patients who have HER-2/neu-positive breast cancer is greater than indicated previously by IHC/FISH. Thus, the number of patients classified incorrectly as HER-2/neu negative could be substantially greater than recognized previously. This feature review presents a HER-2/neu testing algorithm that combines the serum HER-2/neu test result with IHC/FISH test results to maximize the identification of patients who are HER-2/neu positive and could be potential candidates for HER-2/neu-targeted therapies. The HER-2/neu situation also exemplifies that multiple diagnostic tools are required to correctly and accurately identify patients for targeted therapies--an important lesson as many new biomarkers are identified for the multitude of new targeted therapies in development for various forms of cancers.
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PMID:Hidden HER-2/neu-positive breast cancer: how to maximize detection. 1935 Apr 68

Receptor tyrosine-protein kinase erbB-2 (HER2)-positive breast cancer is a specific entity with an aggressive behavior. Trastuzumab, a monoclonal antibody targeting erbB-2 (HER2) deeply transformed the outcome in patients. Nevertheless, resistance to trastuzumab is still a major concern. Lapatinib ditosylate is an orally available, small molecule targeting the tyrosine activity of the HER2 receptor. Lapatinib as a single agent and in combination therapy showed interesting activity in trastuzumab-resistant advanced tumors. In addition, lapatinib use seemed suitable in recurrent locally advanced inflammatory breast cancer and brain metastases. More recently, the Neo-ALTTO (NeoAdjuvant Lapatinib and/or Trastuzumab Treatment Optimisation) trial showed that lapatinib in combination with trastuzumab and paclitaxel significantly improved the pathological complete response in a neoadjuvant setting. Several clinical trials are still ongoing and data that may change current clinical practice are awaited with much interest.
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PMID:Lapatinib ditosylate: expanding therapeutic options for receptor tyrosine-protein kinase erbB-2-positive breast cancer. 2201 64