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Becky 02-03-2013 06:23 AM

Tumor Profiling Lab Tests
 
This information is from Mamacze and I am kindly "sticking" it on her behalf. Thank you Kim!
-----------------------------------------------------------

I am adding this sticky to alert our Her2 members to the recent option of tumor profiling lab tests. When your physician sends a biopsy sample for molecular testing to a lab that does tumor profiling, the lab can run a panel that is tailored specifically to each tumor, resulting in a uniquely focused and targeted diagnosis. The report provides you, (the patient) and your oncologist with lists of relevant clinical trials that are tied to the specific diagnosis, if a mutation is identified. I encourage any of you, especially if you are resistant to treatment to consider having this done.
I am familiar with the lab Precipio Diagnostics at Yale in New Haven, CT. (
http://www.precipiodx.com/patients_tumor_profiling.html) I am sure there are others out there. Personally, I would work with a university-based lab as they may provide additional analysis that a more traditional for-profit lab may not be reimbursed for. I have received many queries about this so I have asked Becky to sticky this message.

Joan M 02-05-2013 10:47 AM

Re: Tumor Profiling Lab Tests
 
I've been skeptical about the new wave of tumor profiling in breast cancer, and I'm still uncertain what to think about it. The question seems to be about clinical relevancy.

Last year, several posts on the board discussed specific labs and how a tumor profile could perhaps help us determine which chemo drug would work best. As a result, during a Q&A at a local meeting I asked a top breast cancer onc at Sloan Kettering, and he said it was all "fraud." I was shocked, as I didn't expect that kind of an answer. I thought I would get the scoop, and was disappointed at his choice of a such a strong, finite word. But that word clearly conveyed his thoughts on the topic.

The point is that we often have more data than what we know what to do with. Yet these services perhaps make up feel that getting our tumors gene sequenced today is the answer. More to the point, and something that often escapes us, many of these assays are not clinically relevant at this time: That is, they don't translate from the bench to the clinic. So are we raising our hopes and at the same time wasting our time and money? Are these assays just another way for labs to make additional money by giving us information that cannot yet be fruitful? And what about future assays that actually might be relevant?

At SABCS I picked up a flyer from City of Hope's Clinical Molecular Diagnostic Laboratory. It reads: Coming soon ... Next-Gen Sequencing Panels. The photocopied sheet of white paper then listed the panels, the individual genes, and the cost of the assay:

*Onco-44-gene panel, $1,875
*Cancer-30-gene panel, $3,250
*Breast-17-gene panel, $2,350 (ATM, AXIN2, BAP1, BARD1, BRIP1, CDH1, CHEK2, MRE11A, NBN, PALB2, PTEN, RAD50, RAD51C, RAD51D, STK11, TP53, XRCC2)
*Ovarian-22-gene panel, $2,350
*Colorectal-19-gene panel, $2,350
*Cancer-428-gene panel, $3,950

Besides relevancy, another important word is diagnostics. Put simply, for breast cancer: ER/PR, HER2. Assays show us which breast cancer subtype we have and therefore which supplemental treatments work best. That is, a specific diagnostic test corresponds with specific drugs. Further, Oncotype DX is another clinically relevant assay that helps patients and oncs make informed decisions about treatment. The 21-gene assay and its recurrence score is a way for oncs to determine whether or not adding chemo to endocrine therapy would likely be beneficial (except of course for the patients who fall in the middle of the scale, and perhaps the results of the TAILORx trial will eventually result in tweaking that assay or developing a second-generation Oncotype DX).

As a breast cancer advocate, these are the types of questions that I try to remember to ask myself before I get caught up in the hype. Next-gen sequencing is not new, but lately it's become much cheaper than previously. And right now, I don't know where it's going. But I'm optimistic that the seeming quagmire of such sequencing results will some day be the antithesis to the Pandora's Box of cancer that it seems to have opened and help us to beat cancer.

Love
Joan

rhondalea 02-12-2013 07:12 AM

Re: Tumor Profiling Lab Tests
 
Hi Joan,

I'm sorry this is so late. I started a post, but it was gobbledy-gook, so I trashed it.

That top onc is kinda right for now, but he's wrong for the future. At the moment, genetic/epigentic medicine is in its infancy. See for a quick rundown on the numbers we're dealing with:

http://geneticgenie.org/blog/2013/01...of-your-genes/

Up above, you have a list of "gene panels." They're looking at specific snps on those panels, but what about the snps they overlook? And what about the combinations (what SNPedia calls "genosets") they haven't considered?

The day is coming that an individual will be able to have her genome sequenced and know exactly what went wrong and maybe even how to fix it. For now, medicine is hampered by a lack of data. Cheap ($1000) genome sequencing will help fix that, and it's in the pipeline.

The bottom line (in my opinion) is that for the moment, these are the tests we have, and they do give us some useful information, so there's no reason not to use them. Your top onc disagrees. But he's fails to consider that the worst thing that happens by using these tests is that the research will advance for the benefit of those who come later.

Joan M 02-12-2013 08:34 AM

Re: Tumor Profiling Lab Tests
 
Hey Rhondaleah,

It was great meeting you at SABCS.

I would agree that the top onc is wrong for now, but not for the future. However, the future isn't here yet and that's the point.

I guess my argument is that knowing today whether I have a genetic mutation on CHEK2, for example, has cost me a lot of money but it doesn't really get me anywhere.

Perhaps, and that's a big perhaps, City of Hope has a clinical trial for survivors who have that mutation. That is, they're testing a compound for dealing with CHEK2 mutations (CHEK2 is a checkpoint in the cell cycle that's involved in cell cycle arrest and therefore allows only well-behaved cells to proceed in the cycle). But somehow I doubt that. Or perhaps they have a phase 1 trial. When I was first diagnosed at stage 4, I used to bring clinical trial enrollment papers to my onc and she would say, "you're not phase 1 material," even though I guess she was supposed to encourage me to enroll in clinical trials.

You said, "and maybe they'll know how to fix it." Maybe, is the issue. At this point, molecular biologists have little idea of how to fix these mutations which would result in meaningful treatments, even though they're working hard on it. So, these expensive tests really don't serve us now. If I submitted my tumor to the $2,350 breast-17-gene panel, by the time there's a potential treatment for any one of these mutations, there would be a companion diagnostic test, like for HER2, and the expensive gene panel would be useless. Nobody's going to use the results of that gene panel. Survivors would be tested with the diagnostic to determine whether we have the mutation and then enrolled in clinical trials. In the end, we would all be tested for CHEK2 just like we were for ER/PR and HER2.

I don't think it's prime time yet for gene panels, and women like me who have metastatic disease are being duped into thinking that we're going to get something meaningful out of it. We're being taken advantage of.

A breast cancer advocate expressed this well. A slightly different version of what I posted above was uploaded yesterday on a blog and then the advocate who works for the NBCC picked it up on Twitter.

She wrote: A major genomic researcher told me the tests were "unethical." ... Ur thoughts abt new tumor profiling n bc?

The blog then responded.

Then she wrote: Yes, I saw that, not the same person I spoke with. So looks like several researchers have reservations.

An ovarian cancer advocate then responded to her: Good point. Will knowing you have a tp53 mutation change your treatment plan? Research needs to catch up with the data.

Joan

Mandamoo 02-12-2013 09:46 PM

Re: Tumor Profiling Lab Tests
 
Good discussion. I guess some of the interesting things coming from this are the access to phase 1 and 2 trial a for more obscure mutations. So far awareness of me having a tp53 mutation has meant nothing but I have read reports of new trials that may not be cancer type specific that will target such a mutation.
Mamcaze has learned that an mtor inhibitor is likely to ba a best course of action for her next if needed.
I have friends who have needlessly been given taxane based therapy when testing on recurrence has shown it was likely useless all along - cold something more effective have been used up front?

It is in its infancy yes. I am fortunate to be gaining information through donation of tissue to research trials so no cost but takes a long time and yes, to date has not yielded much in the way of fruitful treatment options. (I am currently waiting new results on lung tissue).
As someone for who herceptin has failed right from the start I have to keep looking for options and I hope such testing may be he way and in being part of it - maybe, just maybe I'll get somewhere? Would I pay for a Caris report - doubt it - dint think we would learn much for the - $7000 it costs just yet.

Joan M 02-14-2013 01:54 PM

Re: Tumor Profiling Lab Tests
 
A mutated tp53 is common in cancer in general.

On Tuesday, I asked my oncologist whether patients could be tested for chemosensitivity, and he said, no. Then he mentioned that Precision Therapeutics has such tests and lung cancer oncs seem to go for this type of testing. I think that his "no" probably meant that the tests are not clinically relevant yet. Perhaps that's what "unethical" means in this context: that patients are being charged for a test that really has no clinical use. Or perhaps worse than that: the tests are bogus because the answer is not that simple.

Chemosensitivity tests would be great. Think of how such tests would save patients from having to deal with the side effects of chemo that isn't going to work for them.

One potential way to determine chemosensitivity is through neoadjuvant trials, and I believe that we'll be seeing more of these in the future. Most survivors do not obtain a complete pathologic response in such trials, and residual breast tumors could be used further to determine why not (neoadjuvant chemo is giving it before breast surgery) . These studies are very useful for studying aggressive bc, such as HER2 and triple negative. If a TNBC enrollee achieves cPR, they have a much greater chance of beating bc. Such patients do not yet have supplemental treatments like we do. Here's a 2-minute clip from SABC about testing residual tumors of TNBC patients. I attended Balko's presentation at the conference:

http://www.onclive.com/conference-co...ations-in-TNBC

An mTOR inhibitor might well be the next best place to go regardless of testing. It's being actively studied in bc. There's a phase 1 clinical trial (Merrimack Pharmaceuticals) for HER2+ metastatic survivors, which uses the compound MM-302. An mTOR inhibitor (I think Chrisy was in that trial).

http://clinicaltrials.gov/ct2/show/N...=mm-302&rank=1

According to clinicaltrials.gov, there doesn't seem to be a diagnostic test to indicate whether a survivor is likely to respond to MM-302.

Affinitor is another mTOR inhibitor for women with metastatic ER+/PR+/HER2 negative bc. It's used in combination with Aromasin for postmenopausal women who progressed on an endocrine drug (Bolero2 trial). The drug was recently FDA approved for advanced bc.


I gave my lung and brain nodules over to research and stay in contact with those folks (my brain tumor was HER2 negative). I recently had an email exchange with Sloan. They have a piece of my lung nodule, which was removed by NY Presbyterian/Weill Cornell. They're studying why patients who took Herceptin adjuvantly turned out to be refractory to it. I took it off-label when I was diagnosed with stage 2 in 2003. (I emailed to kindly remind the scientist that, FYI, I've been NED since January 2007 and on only Herceptin since my cancer advanced. So perhaps they need to rethink their refractory concept.) Sloan removed my brain nodule. They aren't doing anything with it yet, but I had a piece sent to Standford U for a study.

Joan

rhondalea 02-14-2013 06:13 PM

Re: Tumor Profiling Lab Tests
 
I'm behind. That's nothing new, but I meant to get back here a lot sooner. Unfortunately, I'm still not quite ready to write the post I feel compelled to write, but I received an interesting email opportunity, and I thought others might be interested:

http://www.cvent.com/events/nccn-201...8ae32c793.aspx

Biomarkers now play a key role in the routine management of patients with cancer and guide drug development in the age of targeted therapy. This webinar series will address the demand for reliable, practical information about biomarkers and their appropriate use, biomarker testing, application of test results, and clinical utility of biomarkers.

I haven't registered yet, but apparently these are free webinars.

Joan M 02-15-2013 11:24 AM

Re: Tumor Profiling Lab Tests
 
Your right, Amanda, this is a good discussion. Thanks for the link, Rhondalea.

Joan

chrisy 02-15-2013 12:23 PM

Re: Tumor Profiling Lab Tests
 
I agree, great discussion - slight correction, MM302 does not target MTOr, it is an ADC (antibody drug congugate), same theory as TDM1 with a her2 target/doxil.

Joan M 02-15-2013 12:37 PM

Re: Tumor Profiling Lab Tests
 
Chrisy, thanks for pointing that out and joining the discussion. I guess you would know, since you were in the MM-302 trial.

In general, here's a link to further information on the compound:

http://www.news-medical.net/news/201...st-cancer.aspx

Joan

mamacze 02-18-2013 01:45 PM

Re: Tumor Profiling Lab Tests
 
Thank you all for chiming in on my post and thank you Becky for putting a thumb tack on it.
I too am concerned for patients who have tumor profiling done and can do nothing with the results - ie, when we have no effective treatments for the mutations that are identified.
But (correct me if you think I have been duped, please!!), when I had the profile done;
a gene mutation was identified (PIK3CA G1049S); and the tumor profile report also then identified a promising med that has shown clinical benefit in clinical trial against that particularmutation. (in my case they identified Drugs Associated with Clinical Benefit against this mutation ie, Everolimus or other mTor inhibitors) They also listed relevant available clinical trials with a link on clinical trials.gov. At the moment I am still responding to Herceptin (the tumor they biopsied is what popped up during a Herceptin holiday). But I feel like I have Everolimus in my back pocket as a Plan B when I start to become resistant to Herceptin.
Also,they said this test was covered by my insurance.
My oncologist was intrigued. He said he would get another biopsy done when I do become resistant to Herceptin. I queried the company that did the profiling. They said they only report on mutations that have a corresponding drug associated with clinical benefit; otherwise the test is not helpful to patient or physician.
Do you think I was misled?
I would love to hear your opinions.
Love this Her2 board....
Kim (from CT)

Joan M 02-18-2013 06:53 PM

Re: Tumor Profiling Lab Tests
 
Kim,

It's great that you have reached NED, and that the lung tumor is now stable with only Herceptin!!

Sometimes I think there are a lot of "ifs" and that the devil is in the details when it comes to chemosensitivity testing.

You're a pioneer here!! Which FDA-approved drugs did the lab suggest for your mutations? Are the drugs for only breast cancer patients or for patients with other cancers or medical conditions? Although that might not matter much. Everolimus (Affinitor) was originally approved by the FDA for another disease and now has several other approvals. In 2012, they approved it for advanced breast cancer patients who are hormone receptor positive, HER2 negative, in combination with exemestane (Aromasin). I noticed that you were hormone positive when you were stage 0. Are your mets the same?

It seems that the lab's list may be for general breast cancer patients and perhaps other cancer patients as well. But the therapy could be helpful even though you are HER2+. The FDA approved the drug combination based on the clinical trial criteria (nothing more, nothing less), but that doesn't mean that it won't work in other circumstances.

http://www.cancer.gov/cancertopics/d...fda-everolimus

Were the suggested clinical trials for only advanced breast cancer patients? And was having the mutation the only criteria for the trial?

I would be open to using drugs already approved by the FDA for other cancers or purposes, as well as clinical trial drugs connected to a particular mutation.

http://www.mskcc.org/cancer-care/adu...-trials/12-155

I don't think that genetic tests are not necessary good. My only concern was that some cancer patients might think that they're the answer. If the patients' eyes are open it doesn't seem like it's a problem.

Joan

Mandamoo 02-18-2013 09:20 PM

Re: Tumor Profiling Lab Tests
 
The have been studies on using affinitor in her2 patients - bolero 1 and 3 - my understanding is they have not been published yet and while not as outstanding as Bolero 2 results still positive. I was in a bolero 3 trial. I have a friend currently NED for 2 years since this trial - kept me stable for 7 months - best response I've had stability wise.

I just think this testing is very much in its infancy and without people like us willing to trial some of the drugs they will not know how much clinical benefit there is to the knowledge gained.

Kim I think it's wonderful you know more about your tumor and its possible treatments.

Bebe 02-21-2013 04:03 PM

Re: Tumor Profiling Lab Tests
 
I am new member of this forum. I had left mastectomy last May 2011 after undergoing chemo and Herceptin. Herceptin was continued every 3 weeks until December 2011. My cancer recurred on September 2012. At first I had Herceptin from October until December of which instead of shrinking the originally 2 lymph nodes as seen on PET/CT scan, the lymph nodes grew in size and number. I had surgery last Feb 6, 2013. The pathology report after excision: the tumor 2.5 cm on my left chest wall indicated recurrent invasive ductal carcinoma, involving peripheral soft tissue margin, extensive lymph-vascular invasion. Lymph nodes axillary dissection: metastatic carcinoma involving 3 lymph nodes with extracapsular extension (3/3), largest - 5 cm. Lymph node, highest level 2 lympadenectomy: metastatic carcinoma involving one lymph node with extracapsular extension (1/1). I am waiting for my appointment with my onco on Feb 26, 2013. Does anyone had similar situation? My onco before I had my surgery told me that I have to undergo radiation after the scar is healed. Does anyone knew about any other treatments/clinical trials? thanks!

mamacze 02-22-2013 02:15 PM

Re: Tumor Profiling Lab Tests
 
Hi Bebe,
Welcome to the boards! I am so sorry to hear about your lack of response to Herceptin. Please re-post your note on the main Her2 message board - there are many many girls who share your experience who, when seeing your post will want to jump in with advice.
Hang in there honey and I am so glad you found us!
Hugs,
Kim (from CT)

mamacze 02-22-2013 02:35 PM

Re: Tumor Profiling Lab Tests
 
Hi Joan (and sweet Amanda et al!),

Me again...thank you for your thoughtful responses.
It looks like you too, Joan, share this nice long dance
with NED. I am sure you are making the most of it. To answer your questions:

Which FDA-approved drugs did the lab suggest for your mutations?

Precipio Diagnostics Lab report states that "The mTor inhibitor everolimus, used in combination with aromatase inhibitors, has recently been shown to improve the outcomes of women with HR-positive breast cancer who have failed prior treatment with aromatase inhibitors alone.(Baselga et.al 2012)"
and as you know, according to cancer.gov:
"On July 20, 2012, the FDA approved everolimus tablets (Afinitor®, made by Novartis Pharmaceuticals Corporation) for the treatment of postmenopausal women with advanced hormone receptor-positive, HER2-negative breast cancer in combination with exemestane, after failure of treatment with letrozole or anastrozole. "

Yes my mets are still Her2+++.

Fortunately for me, my tumor is still responding to regular infusions of Herceptin. But it is nice to know the above tumor information in the event I have an urgent need for a Plan B.


Were the suggested clinical trials for only advanced breast cancer patients? And was having the mutation the only criteria for the trial?

No the suggested clinical trial is not only for metastatic breast cancer but for other cancers as well. The mutation was one criteria among others for eligibility.

Overall I found the tumor profiling report to be informative and quite helpful. I certainly don't think it is "the answer" for all metastatic patients, but for those of us who have mets and who are also found to have a treatable mutation - golly; I just don't see a downside.

Also as a pleasant aside; my insurance confirmed to me yesterday that this tumor profile test is covered.

Thank you again Joan and Amanda Chrisy and Rhonda for your great feedback. We need to continue linking arms, be vigilant and strong as we seek out and use new diagnostic and treatment modalities!

Love you all,
Kim (from CT)

bhd1 02-25-2013 10:23 AM

Re: Tumor Profiling Lab Tests
 
how can tumor profiling be helpful if your onc does not believe in it?

mamacze 02-25-2013 11:13 AM

Re: Tumor Profiling Lab Tests
 
Hi bhd1, and Welcome!
It sounds like you met with your oncologist and discussed the idea of tumor profiling? Do you have mets? Are you responding to your treatment now?
Thank you for logging in - perhaps we can help if you are comfortable sharing a
bit more information about your circumstances. Hang in there.
Hugs,
Kim (from CT)

bhd1 02-25-2013 11:27 AM

Re: Tumor Profiling Lab Tests
 
Yes I have mets. Tdm1 just failed me on first scan. My onc is not into tumor profiling. So what would I do w the results?

mamacze 02-26-2013 12:20 PM

Re: Tumor Profiling Lab Tests
 
I am so sorry you failed TDM 1. I will send you a PM and if you want I can share my own experience - not sure if it will be helpful; but it surely can't hurt...


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