Navigation Links
Breast Cancer and HER-2/neu: Diagnostic Tools for Targeted Therapy


Michael S. Singer, M.D., Ph.D.
Harvard Medical School
Contributing Editor

With over 200,000 new cases and 40,000 deaths per year, breast cancer undoubtedly qualifies as one of Americas most serious health problems. Recently, efforts to develop early detection methods and more effective therapy have made important progress. This is particularly true at the molecular level, where discoveries on protein expression have translated into new diagnostic tests and targeted therapies. An example is the finding that tumors expressing estrogen receptors (so called ER+ tumors) tend to respond to tamoxifen, a selective estrogen receptor modulator. Conversely, ER tumors tend to respond better to chemotherapy and not to tamoxifen. Another revolutionary example is that of Her-2/neu protein (also called c-erbB2), which is overexpressed in approximately 2530% of breast cancers. With herceptin (trastuzumab) and other preferential medications available to treat these patients, the need has emerged for routine laboratory methods to detect Her-2/neu overexpression. A wide array of tools has arrived to fulfill this purpose.

Human cells normally carry and express two copies of Her-2/neu, which is located on chromosome 17 and encodes a cell-surface receptor for epidermal growth factor. Like many growth factor receptors, Her-2/neu functions as a tyrosine kinase and moves cells forward on the cell cycle, which involves DNA replication and cell division. Her-2/neu therefore falls into the class of proto-oncogenes. A key discovery is that some 2530% of breast cancers carry amplifications (multiple copies) of the Her-2/neu gene, which lead to overexpression of Her-2/neu protein. The over-abundance of Her-2/neu receptor accelerates the cell cycle and causes cells to divide more rapidly and haphazardly. This explain why Her-2/neu overexpression is associated with more rapid tumor growth and a worse prognosis.

Th e real value of the Her-2/neu discovery, and one that helps to counter the poor prognosis of Her-2/neu positive tumors, is that specific therapies such as adriamycin have proven more effective for patients with these tumors. The most celebrated medication, however, is probably Herceptin, (trastuzumab) a chimerized human-mouse monoclonal antibody that binds an exposed portion of the Her-2/neu receptor on the cell surface. Herceptin has been shown to shrink and even eliminate some tumors. Compared to chemotherapy alone, the addition of herceptin reduces tumor recurrence by half. Herceptin has thus earned a place as first-line therapy for qualified patients.

FDA-approved kits use one of three methods to quantify Her-2/neu overexpression in breast tumors. The first is immunohistochemistry (IHC), which involves a semiquantitative, microscopic assessment of antibody reactivity on a fixed tissue sample. Studies have shown that when specimens are carefully handled, IHC results correlate well with Her-2/neu copy number. The test uses a conventional microscope, can be automated, and has a relatively low cost. Some challenges of IHC include consistent tissue preparation and control assays. Commercially available and FDA-approved IHC kits include the InSite Her-2/neu kit (BioGenex), available in both manual and automated forms. The automated form is compatible with the BioGenex i6000 system. Other tests, which can also be automated, are the HercepTest (Dako Corporation) and PATHWAY (Ventana Medical Systems). The Ventana PATHWAY offers an integrated system of IHC plus a reflex FISH assay (see below).

Fluorescent in situ hybridization (FISH) involves the hybridization of specific DNA probes, which are visible on a fluorescent microscope. FISH is compatible with all kinds of tissue, whether fixed or not. Like IHC, FISH is also amenable to automation. A particular benefit of FISH is that it contains an internal control: a chromosome 17 probe not asso ciated with Her-2/neu. An excess of Her-2/neu probe fluorescence over control probe fluorescence indicates Her-2/neu amplification. Challenges of FISH include higher cost and the need for a fluorescent microscope. One commercially available kit is the Ventana INFORM, which works in concert with the IHC system mentioned above. Other FDA-approved kits are PathVysion (Abbott-Vysis) and the Her-2 FISH PharmDx kit (Dako USA).

ELISA is also available to quantify Her-2/neu expression. In contrast to IHC and FISH, ELISA can detect Her-2/neu as a serum marker. This bypasses the need for a tissue specimen and may allow earlier Her-2/neu detection. The Her-2/neu ELISA (Bayer Diagnostics Oncogene Science) is a sandwich-type immunoassay approved to monitor patients with known metastatic breast cancer.

With other methods such as RT-PCR on the horizon, one can expect further evolution of the diagnostic and therapeutic landscape. Along with it comes the promise of similar solutions for other cancer patients.
'"/>




Related medicine technology :

1. New Advances in Gastric Diagnostics: Smaller is Better
2. West Nile Virus Screening and Diagnostics Technology Emerges In Step with North American Outbreak
3. Non-Invasive Diagnostic Tests for Celiac Disease
4. Bench-Top Centrifuges--Basic Tools for the Small Lab
5. Appendicitis: Evolving Tools to Diagnose a Classic Disease
6. Gene Chips to Detect CYP Variations: A New Step Toward Customized Medical Therapy.

Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/24/2016)... , June 24, 2016 ... appointment of Dr. Edward Futcher to ... Director, effective June 23, 2016.Dr. Futcher was also ... and Governance Committees.  As a non-executive member of ... expertise and strategic counsel to VolitionRx in connection ...
(Date:6/23/2016)... Calif. , June 23, 2016 Any dentist ... many challenges of the current process. Many of them do ... of the technical difficulties and high laboratory costs involved. And ... to offer it at such a high cost that the ... it. Dr. Parsa Zadeh , founder of ...
(Date:6/23/2016)... 2016 Research and Markets has announced ... Analysis 2016 - Forecast to 2022" report to their ... contains up to date financial data derived from varied research ... trends with potential impact on the market during the next ... which comprises of sub markets, regional and country level analysis. ...
Breaking Medicine Technology:
(Date:6/24/2016)... ... June 24, 2016 , ... The ... in Dallas that it will receive two significant new grants to support its ... PHA marked its 25th anniversary by recognizing patients, medical professionals and scientists for ...
(Date:6/24/2016)... CA (PRWEB) , ... June 24, 2016 , ... ... is now offering micro-osteoperforation for accelerated orthodontic treatment. Dr. Cheng has extensive experience ... Damon brackets , AcceleDent, and accelerated osteogenic orthodontics. , Micro-osteoperforation is ...
(Date:6/24/2016)... ... 2016 , ... Topical BioMedics, Inc, makers of Topricin and MyPainAway Pain Relief Products, join The ... raise to $12 an hour by 2020 and then adjusting it yearly to increase at ... the minimum wage, assure the wage floor does not erode again, and make future increases ...
(Date:6/24/2016)... (PRWEB) , ... June 24, 2016 , ... ... today at the Clinical Decision Making in Emergency Medicine conference in Ponte Vedra ... authored journal articles published in Emergency Medicine Practice and Pediatric Emergency ...
(Date:6/24/2016)... ... June 24, 2016 , ... Puradigm® & Innovative Solutions today ... cultivation and processing operations at its production facility, and opened its first two ... the manufacturer of a complete system of proactive air and surface purification solutions ...
Breaking Medicine News(10 mins):