Test for Mutations

I had this test done and the results will be back 2/12/13.

It was in the Wall Street Journal on 12/29/12 and I took the article to my Onc and he contacted them and made arrangements. The test was performed on prior biopsy from my lung. They said they would work with my insurance company, or something about there being funding?

Matching a Tumor to a Drug....Our growing understanding of the workings of the human genome is posing a new challenge. How to use the data to change the course of disease. Consider cancer. As seen through a gene sequencing machine some cancers can appear as at least a dozen different genetic diseases, some of which have been shown to respond uniquely to a specific drug. But how do doctors quickly match a patients tumor with a drug that targets it?

One answer is a test developed by Foundation Medicine Inc. a Cambridge Mass startup whose scientific founders include one of the leaders of the Human Genome Project.. The test, officially launched last June enables doctors to test a tumor sample for 280 different genetic mutations suspected of driving tumor growth.

This changes everything in terms of how we approach patients with cancer says David Spigel, director of lung cancer research at the Sarah Cannon Research Institute in Nashville, Tenn. He used the test in one patient with advanced disease and few apparent options. She turned out positive for an alteration in a gene targeted by several drugs currently in development. She signed up for one of the studies. A short time later she is like a new person he says. She's off pain medicine. She gained her weight back.

Michael Pelini, Foundation's chief executive officer, says that more than 600 oncologists have requested the test, which lists for 5,800.So far he says, about 70percent of cases have turned up a mutation that is potentially targeted by a drug on the market or in a clinical trial.

In one recent case, Dr. Pellini says, a sample from a woman with advanced pancreatic cancer yielded a response for "her2" an alteration associated with a certain form of breast cancer. She was treated and her cancer responded to the breast cancer drug Herceptin. Few oncologists would think to look for her2 in a patient with pancreatic cancer, he said.

NOTE: I've gone through a lot of chemos in a short time and hope this will direct me to the best clinical trial eventually. Janz

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Wow, this is great!!! How do I sign for this test? Where do they do it? I want to know more about this test. Sounds promising. Thank you for sharing this information and good luck with your results. Keep us posted.

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Janz, Are you talking about the ELISA testing?

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Thanks for sharing!!!!! keep us posted.

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Warrior1, not sure, havent heard the word ELISA before. What is ELISA testing? You might google the company name. Very interesting startup company that Bill Gates has invested in. There was also an article in the Boston Globe about 2 weeks ago (per "Phil" on this website).

I will share more when I get my test results!

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Here is the info on 'ELISA' test, approved by FDA. It is, essentially a test for checking Her2 status, by testing blood, instead of a sample of mets.


HER-2/neu ELISA A test for quantitation of human HER-2/neu oncoprotein levels in serum (blood) Item # 06489876

HER-2/neu ELISA controls (3 0.5 ml vials: High, Mid,Low Levels) Item # 06489884

Intended Use

The Oncogene Science HER-2/neu ELISA is an in vitro, diagnostic device intended for use in the quantitative determination of serum HER-2/neu in women with metastatic breast cancer who have an initial value of 15 ng/ml or greater. HER-2/neu values obtained may be used in the follow-up and monitoring of patients with metastatic breast cancer. HER-2/neu values should be used in conjunction with information available from clinical and other diagnostic procedures in the management of breast cancer.n The clinical utility of the serum measurement of HER-2/neu as a prognostic indicator for early recurrence and in the management of patients on immunotherapy regimens has not been fully established.

Metastatic Breast Cancer

Monitoring Serum HER-2/neu to Help Manage


Metastatic breast cancer (MBC) patients who overexpress the HER-2/neu protein tend to have a worse prognosis and a more aggressive disease that can be resistant to certain types of chemotherapy [1]. HER-2/neu protein overexpression is determined by running a tissue test like immunohistochemistry. If a patient overexpresses the HER-2/neu protein, they are considered HER-2/neu-positive and a candidate for HER-2/neu-targeted therapy such as trastuzumab. HER-2/neu-targeted therapy is helping to improve survival rates for HER-2/neu-positive, MBC patients everywhere [2].

Serum HER-2/neu testing does not determine HER-2/neu overexpression but is complementary to tissue testing because it can be used to help monitor certain patients on HER-2/neu-targeted therapies once tissue testing already has established that the patient overexpresses HER-2/neu. The serum HER-2/neu ELISA measures a portion of the protein present on the outside surface of cells. This portion, often referred to as the extracellular domain (ECD), can cleave off into the blood of MBC patients. Serum HER-2/neu testing can measure the amount of HER-2/neu ECD shed into the blood.

The HER-2/neu ELISA is a simple, non-invasive serum test that can be used as a clinical tool for monitoring and managing certain patients with MBC when used in conjunction with clinical and other diagnostic procedures. When serum values are equal to or greater than 15 ng/mL, the test can be used to monitor a patient’s HER-2/neu status and has been shown to parallelthe clinical course of disease regardless of a patient’s treatment regimen [3-8]. Increasing levels in serum can reflect disease progression while decreasing levels can reflect treatment response or stable disease [8-13]. Monitoring the changes of serum HER-2/neu levels can help manage these metastatic breast cancer patients. The clinical utility of serum measurement of HER-2/

in the


of recurrence








management of patients on immunotherapy regimens has not been fully established.

Establish a Baseline Serum HER-2/neu

Upon a diagnosis of MBC, a baseline serum HER-2/neu level should be established. Patients with an initial serum HER-2/neu level equal to or greater than 15 ng/mL should have subsequent monitoring. Regardless of whether a HER-2/neu tissue test is negative or positive for overexpression of HER-2/neu, it is important to establish a serum HER-2/neu baseline. Some studies have noted a possible discordance between HER-2/neu expression in primary versus metastatic breast cancer tumors [14,15]. However, serum HER-2/neu levels can become elevated in patients whose initial serum HER-2/neu value was less than 15 ng/mL [16]. This may indicate a change in HER-2/neu status as a resultofdisease progression.

Use In Conjunctionwith Other DiagnosticProceduressuch asTraditional Tumor Marker Tests

Unlike traditional tumor markers, the HER-2/neu oncoprotein, which is quantitatively measured by the serum HER-2/neu ELISA, is derived from a known oncogene which is biologically involved in converting normal cells to cancer cells. Serum HER-2/neu testing can offer a real-time assessment of a patient’s HER-2/neu status. A number of studies have investigated the clinical utility of monitoring serum HER-2/neu in conjunction with other diagnostic procedures such as tumor marker tests [8,17,18]. In particular, Dnistrian AM et al. found that measuring serum HER-2/neu levels in conjunction with certain tumor markers helped monitor patient response to targeted therapy [18].

Monitor the CourseofDisease Regardless ofTherapy

As previously mentioned, many studies of patients with MBC receiving hormone or chemotherapy have shown that longitudinal changes in serum HER-2/neu levels reflect the clinical course of a patient’s disease [9]. Other reports indicate that patients with MBC whose serum HER-2/neu level remained below 15ng/mL when monitored over a period of time were responding to certain therapies [5,11,13]. Numerous studies have evaluated the clinical utility of monitoring serum HER-2/neu levels in MBC patients treated with several types oftherapies, including trastuzumab plus various combinations of chemotherapy.

Principle of the Assay The Serum HER-2/neu ELISA test is a sandwich enzyme immunoassay that utilizes a











monoclonal antibody for the detection of human HER-2/neu protein. Both capture and detector reagents specifically bind to the extracellular domain ofHER-2/neu protein. The Capture Antibody has been immobilized on the interior surface of microtiter plate wells. To perform the test, an appropriate volume ofspecimen is incubated in the coated well to allow binding of the antigen by the Capture Antibody. The immobilized antigen is then reacted with the detector antiserum. The amount of Detector Antibody bound to antigen is measured by binding it with a streptavidin/horseradish peroxidase Conjugate, which then catalyzes the conversion ofthe

product. The







colored reaction product is quantitated by spectrophotometry and is related to the

instructions, see the Detailed


the sample.



amount of HER-2/neu

Protocol and Evaluation of Results sections of the assay protocol.

Results are available in one day for customers who require a standardized, reliable result for comparing values within the laboratory or between laboratories.


Purchase of this kit licenses its use under the following U.S. patents 5,401,638and 6,861,511.


*A study funded with Oncogene Science ELISA kits.

Burstein HJ. The distinctive nature ofHER2-positive breastcancers. N EnglJ Med.2005 Oct 20;353(16): 1652-4.

Brufsky AM, Mayer M, Rugo HS, et al. Central nervous system metastases in patients with HER2-positive metastatic breast cancer: incidence, treatment, and survival in patients from registHER. Clin Cancer Res.2011 Jul 15;17(14):4834-43.

KoestlerWJ, Schwab B, Singer CF, et al. Monitoring of serum HER-2/neu predicts response andprogression-free survival to trastuzumab-based treatment in patients with metastaticbreast cancer. Clin Cancer Res 2004;10(5): 1618-1624.

Esteva FJ, Cheli CD, Fritsche H,et al.ClinicalUtilityofSerum HER-2/neu in Monitoring and Prediction of Progression-free Survival in Metastatic Breast Cancer Patients Treated with Trastuzamab-based Therapies. Breast Cancer Res, 2005. 7(4): R436-R443.

Schippinger W, Regitnig P, Bauernhofer T, et al. The course of serum HER-2/neu levels as an independent prognostic factor for survival in metastatic breast cancer. Oncol Rep 2004;11(6): 1331-1336.

Schondorf T, Hoopmann M, Warm M,et al.Serologicconcentrations of HER-2/neu in breast cancer patients with visceral metastases receiving trastuzumab therapy predict the clinical course.Clin Chem 2002; 48:1360-1362.

Schwartz MK, Smith C, Schwartz DC, et al. Monitoring therapy by serum HER-2/neu. Int J Biol Markers 2000;15: 324-329.

Fehm T, Gebauer G, Jager W. Clinical utility of serial serum c-erbB-2 determinations in the follow-up of breast cancer patients. Breast Cancer Res Treat 2002; 75: 97-106.

Esteva FJ, Valero V, Booser D, et al. Phase II study of weekly docetaxel and trastuzumab for patients with HER-2-overexpressing metastatic breast cancer. J Clin Oncol 2002;20(7): 1800-1808.

Colomer R, Montero S, Lluch A, et al. Circulating HER-2 extracellulardomainand resistance to chemotherapy in advanced breast cancer. Clin Cancer Res 2000; 6:2356-2362.

Ali SM, Carney WP, Esteva FJ, et al. Serum HER-2/neu and relative resistance to


trastuzumab-based therapy in patients with metastatic breast cancer. Cancer. 2008 Sep 15; 113(6): 1294-301.

Sørensen PD, Jakobsen EH, Langkjer ST, et al. Serum HER-2 concentrations for monitoring women with breast cancer in a routine oncology setting. Clin Chem Lab Med, 2009.47(9): 1117-23.

Lipton A, Leitzel K, Ali SM, et al. Human epidermal growth factor receptor 2 (HER2)


extracellular domain levels are associated with progression-free survival in patients with HER2-positive metastatic breast cancer receiving lapatinib monotherapy. Cancer. 2011 Nov 1;117(21): 5013-20.

Zidan J, Dashkovsky I, Stayerman C, et al. Comparison of HER-2 overexpression in primary breast cancer and metastaticsites and its effect on biological targeting therapy of metastaticdisease. Br J Cancer. 2005 Sep 5; 93(5): 552-6.

Lower EE, Glass E, Blau R, Harman S. HER-2/neu expression in primary and metastaticbreast cancer. 1: Breast Cancer Res Treat. 2009 Jan;113(2): 301-6. Epub 2008 Feb 14.

*16. Carney WP, Brown-Shimer S, Hamer PJ. Serum HER-2/neu testing can identify HER-2/neu positive patients previously classified as negative by tissue testing. American Association for Clinical Chemistry Annual Meeting Proceedings, 2008. Clin Chem Vol 54(56) Suppl, pg A130: Abstract No.

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Foundation One does testing of the tumor sample removed during your surgery. They test for hundreds of DNA mutations and based on findings tell you about option treatments or clinical trials available. 1 mm cube is needed for the test.

Also, The new entity--dubbed the Institute for Precision Medicine at Weill Cornell and NewYork-Presbyterian/Weill Cornell Medical Center--will use "state-of-the-art technology to enable genomics sequencing.


http://www.fiercehealthit.com/story/weill-cornell-newyork-presbyterian-team -personalized-medicine-hub/2013-01-31

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Does anybody know more info on -
Institute for precision medicine announced in above link.

Do they product? Or not available yet?

Agree on Founationmedicene.

But in wife case being nneuroendocrine high grade metastatic breast cancer.

For second opinion or to confirm-
Are there any other companies does similar to Founationmedicene?
Either in USA or outside Usa?

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Is this the same as the CarisTargetNow tumor testing?

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Caris testing, if I'm not mistaken..........tests the metabolic pathway, for mTOR, TORC 1.
The ELISA testing is for HER2 status, and is done with a BLOOD sample...........INSTEAD OF A TUMOR SAMPLE. Which is pretty amazing. So, this ELISA testing is much easier than trying to get a tumor sample to check for Her2 mutations. It's brilliant.

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Thanks for the info warrior1. Looks very intresting.

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Hi Janz,
Boy!!! I just read your profile and you really have been through the ringers haven't you???
This procedure sounds really interesting. I have just visited the site. I hope for only the very best results for you.
They didn't have much information about breast cancer so perhaps you will 'blaze the trail' for us.
Best wishes.... with your past results one would have to think that you must have a few mutant genes!!!
Fingers crossed for you.

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Thanks Warrior1 for all the info. This test is not ELISA though I figured out after reading your stuff.

jofar, thanks for fingers crossed!

I am traveling so not checking site as often.

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I got in touch with Foundation One a few weeks ago (recommended to me by Dr. David B. Agus,M.D. author of "The End of Illness". They are working to get Medicare to pay for this, although it may take a couple of years. In the meantime, the cost is over $5500 and in the fine print they say, if Medicare does agree to pay, the client will be responsible for payment. Ouch!!

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I received my results. These are the mutations:

CCND2. 2 clinical trials, both phasem1

TP53. No trials

FGF23. No trials

FGF6. No trials

I noticed that the doctor had the lab send a sample from 5/6/2010 breast lumpectomy and not from 6/24/2011 lung metastasis and so am pursuing explanation of why they would send the older sample.

I am sharing this just in case you were curious. All of the mutations identified came with an explanation of what they are.


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for tp53 seem like there is phase2 trail MEK-1775.
http://bethesdatrials.cancer.gov/clinical-research/search_detail.aspx?Proto colID=NCI-13-C-0032

for rictor amplification: anybody following mTOR torc2 inhibitor clinical trail? (e.g BEZ235)

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Satamara, thanks for,the trial reference.

That mk-1775 trial talks about p53 and not that I can see tp53??

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p53 is same as tp53.

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Does anyb
ody know any other molecular testing as good foundation medicine to double confirm?

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I think P53 is the same as tP53- just naming difference...Tumor Protein (tP53)/P53 according to Wikipedia..P53 is called the guardian of the genome..Most cancers trace at least some origin or effect thereof from P53 mutations-Either initial or late stage mutations on a path to tumor development.
I don't think it is relevant to this discussion but TP53 is the last mutation that occur when colon polyps develop to become a colon cancer in a hereditary Colon Cancer (APC gene deletion).
Furthermore,LiFraumeni syndrome, which is s constellation of early occurring familial cancers from Breast,colon etc, P53 is the gene which is deleted or affected.

In cases of breast cancer without familial LiFraumeni syndrome , may be the assumption or hypotheses is that tumor developed due to the tumor suppressor genes(TP 53 or RB) have become dysfunctional to avert the situation . Abnormal cell division(tumor) are led to their apoptosis or cell death through the work of TP53.

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I think they have funding to help people with cost of test. I thought it would be 5,500 but was billed 1,900. The insurance company paid about 700.

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