Genetic testing-how useful is it?

[HopingForTheBest1]

My experience with genetic testing is as follows-

Was initially introduced to this concept when I had my biopsy in June 2018, and had samples sent two separate times to Foundation Medicine. Not enough tissue available to perform their test of approximately 400 genes.

Several months later I was told about the Color saliva 30 gene cancer test. Easy enough to do, and not at all costly. Came back positive for BRCA2, which likely explains why I now have APC. Have done a lot of research on this, and have met two well regarded genetic researchers/oncologists. I expect that after I become castrate resistant from my current therapy (6-7 months now of Eligard, Zytiga, Prednisone and Xgeva) I will need to consider a PARP inhibitor such as Olaparib or Rucaparib.

On Nov 14 had robotic prostatectomy as part of SIMCAP clinical trial. Asked surgeon to make sure that a sample be sent to Foundation Medicine for genetic testing. Was told I didn't need to bother as I will be getting full genetic mapping as part of the trial. Will be following up on this at my next MO meeting in a few weeks.

I am hopeful that I will be able to have targeted/precision therapy based on my own genetic makeup. Has anyone had any type of genetic testing, and what has been your experience?

Happy new year to all.

[Lyubov]

Hard to keep up with the changes in these areas, isn't it? That's why this site is so great & contributions such as yours so helpful.

[Ran2599dy]

Do you happen to know the difference between the Guardant Health 360 test and the Foundation One Test. I had the Guardant test two years ago with no mutations. Also, with PC how often should you have one of these tests?

[Hidden in reply to Ran2599dy]

To my knowledge, Guardant 360 is a liquid biopsy that looks at circulating tumor cells vs. Foundation One which is a tissue sample biopsy. I do see that Foundation One is also offering a liquid biopsy.

There are advantages and disadvantages to both approaches. There's information online on this subject if you do a search.

[Tall_Allen]

Once you know you have a germline DNA defect (BRCA2), you can be sure that all your metastases have it too. Unfortunately, your prostate tumors are not the same as your metastatic tumors. Metastatic tumors are more evolved and will show more genomic changes.

As you say, PARP inhibitors have demonstrated effectiveness in germline DNA repair defects. Probably, carboplatin will prove to be equally effective. You will have to get them on a clinical trial (or pay an enormous cost out-of-pocket for the off-label drug) - there are a list of clinical trials with various PARP inhibitors in combination with other medicines in this article:

pcnrv.blogspot.com/2018/02/...

There is one other very rare genetic defect (MSI-Hi/dMMR) for which there is an approved therapy - Keytruda. That's it, so far. There are other clinical trials for a few other common somatic (tumor) genomic defects (e.g., PTEN loss, ERG-TMPRSS2 fusion, p53, etc.)

Castration resistance occurs whether or not you use ADT - maybe 2 months faster with it. The BRCA2 drives the genome towards castration resistance faster. Prostate cancer-specific survival is better with ADT, however.

[StayingOptimistic in reply to Tall_Allen]

TA, you said something very interesting here, I have never heard about it :

“Castration resistance occurs whether or not you use ADT - maybe 2 months faster with it. ”

Are you sure about this please?

one of the main reasons I keep delaying it and what I hear from some folks on here is that it makes resistance sets in EARLIER.

please when you have a chance, can you elaborate?

Thanks

[Tall_Allen in reply to StayingOptimistic]

In fact, in another response, I just quoted Dr. Duchesne talking about her TOAD randomized clinical trial of early vs deferred use of ADT. She wrote:

"One of the most thought-provoking findings was that the development of the castration-resistant phase occurred significantly earlier in the men who started treatment after a delay, a counter-intuitive finding. This may again be linked to treating low volume disease before it grows resistant clones."

Here's the full study:

thelancet.com/journals/lano...

Evidence from analysis of pre-ADT prostate tumor tissue is that androgen independence starts early in the cancer's development process:

journals.plos.org/plosone/a...

Androgen receptor (AR) mutations have been identified in metastases - it is part of the natural history of genetic breakdown that occurs as cancer progresses. There are over 1,000 genetic mutations that have been identified. Many code for androgen independence by various mechanisms. The cancer cell "tries" them and the fittest ones survive and replicate the most, coming to predominate over time. ADT may first kill off the hormone-sensitive clones, but the hormone-insensitive clones were always there.

[Hidden in reply to Tall_Allen]

Hi TA,

Your second link is what I've been looking for!

By the way, have you looked over Foundation Medicine's services?

I've checked over Care Oncology, did not see personal benefits, can finess Metformin without buying into their COC protocol, liked you mentioned in another thread.

[Tall_Allen in reply to Hidden]

Foundation One and Caris are major genetic info suppliers. They depend heavily on the genomic characteristics of the biopsied tumor - but we know there is great heterogeneity across tumors. Guardant 360 is a blood test that looks at cell-free DNA, so it probably picks up DNA from lots of metastases. It is not FDA approved, and I've heard it is very expensive (around $4000).

[cfrees1 in reply to Tall_Allen]

I'm curious about that castration resistance statement too. I haven't heard that before. Do you have a source?

[Tall_Allen in reply to cfrees1]

see above

[StayingOptimistic in reply to Tall_Allen]

Thank you, sir

[cfrees1 in reply to Tall_Allen]

That is so interesting. I developed CR after 1 year on Lupron and have been regretting that treatment thinking that I should have waited. This puts my mind at ease. Thanks.

[cfrees1 in reply to cfrees1]

My mutation was also a DNA Repair defect, ATM, so that is what contributed to my advancing to castrate resistance so quickly I guess.

[Jdbnord]

sammamish check this thread

[StayingOptimistic]

Thanks, Nal for the info.

[Ralph1966]

Hi Nalakrats,

Why the Urologist don't check for the genetics of the removed prostate whenever they send it to the pathologest after radical prostatectomy?

Is this because they hope that there will be no recurrence?

Should everyone in this forum who get a biochemical recurrence do genetic check?

[Ralph1966]

Does a PPO insurance cover the expenses?

[Dandellis]

Had genetic testing at Rocky Mtn Cancer Center. Identified the ATM GENE mutation, explains the 9 direct family members deaths of advanced cancers. To date, none of my treatment has been focused on gene mutation. Varly new to APAC, but hopeful for more info/experiences here on HU