Genomic testing

I am right now in what you could call a break from treatment, more specifically a break from chemo. I took Carbo/Taxol successfully in 2012 & again last year with Avastin. I had responded well to Carbo/Taxol; apparently the Avastin regimen I just ended last month didn't work for me. I've just started a 90-day period on the oral pill Arimidex, a hormone suppressant. FYI, I've had no experience with the genomic testing you asked about but just wanted to let you know that there are those docs who suggest a kind of break from chemo. My CA-125 has gone from 2800 upon diagnosis in 2012 to 15 in the summer of 2013; now it's at 44. You should know that I have primary peritoneal cancer, which is treated just like ovarian cancer.

If you want details of my experience, I've written about it at www.CaringBridge.org/visit/CaroleSeaton

Good luck!

Alexandra said:

My experience with Genomic testing

My CA125 has been steadily going up since August 2013 (6), September (60), October (82), November (119). Next test on Tuesday, January 14 - ??? It is my first recurrence after 9 months in remission. I am not doing chemo or anything else. And I won't until I start having debilitating symptoms.

I think that genomic testing is a good idea; it's easier to test in vitro than in vivo and saves time and frustration of getting the type of chemo that is unlikely to work.

When I discussed it with 2 different oncologists, both were skeptical. Their position: with very limited chemo choices available, physician's choice based on their experience is almost always the same as the result of the genomic tumor blueprint. I don't know if that's a fact or they're simply "old school".

The cost of testing is not a issue. It can be done for free through the The Clearity Foundation. You fill out 4 forms available from their website http://www.clearityfoundation.org/, put them in touch with your lab doing the biopsy and they will deal with your insurance and if insurance declines, they will pay for the testing and also take care of the logistics of getting the tissue to their lab. Contact I have is Kathleen (Kathy) Zajchowski, Patient / Database Coordinator, The Clearity Foundation, kathleenz@clearityfoundation.org, direct #: 858-657-0282, Fax 858-657-0265. It took me an hour to fill out the forms and I got approved in like 15 minutes and I'm not even a US citizen. BTW they only deal with recurrent ovarian cancer, meaning that they no longer test newly diagnosed patients.

The real issue for me is that testing requires 3 - 6 cores of fresh tumor tissue, not archived tissue from the original surgery. I can't even get the biopsy done to qualify for the drug trial, leave alone for the genomic testing. Even if I somehow manage to get that biopsy for the trial done, the radiology surgeon refused to take more than 3 cores at the same time as unsafe.

My point is that if you're having new surgery or biopsy anyways, by all means have the testing done at the same time. Getting core needle or open biopsy just for the purpose of genomic testing makes no sense to me.

There is another option for testing, called IMPACT (Integrated Molecular Profiling in Advanced Cancers Trial # NCT01505400). It tests your archived tumor samples and current blood samples.It includes genotyping assays: AKT1, HRAS, AKT2, JAK2, AKT3, KIT, BRAF, KRAS, CDK, MEK1, CTNNB1, MET, EGFR, NOTCH1, ERBB2, NRAS, FGFR1, PDGFRA, FGFR2, PIK3CA, FGFR3, RET, FGFR4, SMO, STK11. All you have to do is sign their consent form and they will do it for free. At least in Canada. Not sure about the US.

Hope that helps.

Above I wrote that I was not able to get fresh tumor tissue for molecular profiling by Clearity Foundation. I had the next best thing done: analyze archival tumor tissue removed during hysterectomy a year and a half ago.  Results came back in October, but no one mentioned them to me until I asked about them yesterday.

In addition to BRCA1+ I have TP53 somatic mutation, called TP53 Y220N. Apparently it's a rare missense mutation, leading to nonfunctional protein product and according to IARC TP53 database there was only 1 prior report of Y220N in ovarian cancer. There is no data on correlation with survival or response to therapy.
If anyone is interested there is a recruiting study of a new drug MK-1775 vs. placebo with Taxol / Carboplatin for platinum-sensitive ovarian cancer with P53 gene mutation (Clinical Trial #NCT01357161).

The question that bothered me the most: is it something that I can pass on to my kid, like BRCA1/2+? I emailed the genetic counselor and she called me this morning with the answer: Somatic TP53 mutations are aquired over lifetime and can not be inherited. They are not found in blood, only in tumors. Germline TP53 mutations can be inherited and cause childhood cancers.

For the most of us who didn't go to medical school, here's some info on TP53 mutations. Somatic mutations in the TP53 gene are one of the most frequent alterations in human cancers, and germline mutations are the underlying cause of Li-Fraumeni syndrome, which predisposes to a wide spectrum of early-onset cancers. Most mutations are single-base substitutions distributed throughout the coding sequence. Their diverse types and positions may inform on the nature of mutagenic mechanisms involved in cancer etiology. TP53 mutations are also potential prognostic and predictive markers, as well as targets for pharmacological intervention. All mutations found in human cancers are compiled in the IARC TP53 Database.

If you're still awake, keep reading here http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2827900/