Interpreting results from hereditary cancer test by color.com

[curious-mind1]

My dad just got his results from the hereditary cancer test by color.com. His oncologist had him take it, but we won't see the oncologist for a few more months. What is the significance of this test result (if any), if it read:

"No genetic mutations were identified."

and the following genes were analyzed:

APC, ATM, BAP1, BARD1, BMPR1A, BRCA1, BRCA2, BRIP1, CDH1, CDK4, CDKN2A (p14ARF), CDKN2A (p16INK4a), CHEK2, EPCAM, GREM1, MITF, MLH1, MSH2, MSH6, MUTYH, NBN, PALB2, PMS2, POLD1, POLE, PTEN, RAD51C, RAD51D, SMAD4, STK11, TP53

I'm guessing his prostate cancer might or may not develop some of these mutations (such as the BRCAs), but even if he doesn't develop any of these mutations, he could still develop resistance to his current Zytiga/Lupron/Avodart regimen?

His ADT is so far controlling the cancer since he went metastatic in 2015.

Thanks,

Arthur

[Tall_Allen]

Color Genome Dx is a "germline" test - it tests for heritable genetic mutations. No mutations is a good thing, and is by far the most common finding. It doesn't test for all genomic mutations that influence PC progression (there are hundreds of them).

An altogether different thing are "somatic mutations." Somatic mutations are genomic alterations that will occur as the cancer progresses. So, yes, he will eventually develop resistance to Lupron and Zytiga.

[curious-mind1 in reply to Tall_Allen]

Thank you, that clarifies things a lot. Is it correct to assume that, if he keeps holding at undetectable for a bit more, the new mutations will take some time to become clinically significant, since his tumor burden should be rather low at this point?

Arthur

[Tall_Allen in reply to curious-mind1]

A low nadir PSA is prognostic for a longer survival.

[curious-mind1]

Thanks. Dad's seeing Dr. Drake in NY now. We're hoping for a long ride on his current ADT, he started with Xtandi in 2015, had bad neurological effects on it, switched to Zytiga in 2015 and that's about it so far (added Xgeva as well this year).

[Tall_Allen]

Genomic breakdown of the cancer always occurs, unless one dies of something else first. It's one of the hallmarks of cancer. AR-V7 is just one of many resistance pathways.

[Tall_Allen]

There is no doubt that cancer is both cell-based and tissue based - no one can argue that. In fact, I have posted the references for both theories. But that the genomic breakdown will eventually continue is incontrovertible - 100% inexorably. Have a good night.

[Joes-dad]

Arthur, I received the same results and that was not what I expected. My father, 2 of his brothers and his nephew have all had prostate cancer and now I have it. I'm happy they didn't find anything but at the same time it makes me wonder if they really did the test or how accurate it was in my case.

Bob

[curious-mind1 in reply to Joes-dad]

Bob,

I do remember reading on the bottom of the test results paper from Color.com, that 80-90% of all cancers are not the result of hereditary inherited mutations. I think doctors give this test to rule out inherited mutations, seems like it is a tool that give doctors a better understanding of the type of cancer the patient is facing. At the same time, they are suggesting that most cancers are the product not of inherited genes, but of complex and multiple environmental factors that we basically don't and can't predict before hand.

Arthur

[Tall_Allen]

Well, if genomic breakdown does not occur, then it is not cancer. So it is 100%. That's what it means to be a hallmark.

[Hidden]

I did the same test back in March with the same result. My father, his two brothers and my maternal great-grandfather all had PCa, none of them died from it. My father is 29 years post diagnosis and rad treatment only back in 1990, still alive. No recurrence and no other treatments. I had IMRT in January and started Lurpon/Zytiga/ Prednesone also. My PSA has been undetectable for 4 months now, I stopped the ADT in April, and will mimic the short-term intermediate use of ADT at Moffit Cancer Center in Tampa. The average time to failure of ADT in the trial went from 16.5 months to somewhere beyond 38 months, they still have not reached that point with the trial participants. Delaying failure by a factor of two or three is a great thing.

[curious-mind1 in reply to Hidden]

Indeed! And hitting the cancer with multiple drugs makes the cancer work much harder in its attempts to resist and overcome the therapies; every oncologist my dad's been with has emphasized this multi-pronged approach to therapy.

With wishes for continued undetectable PSA,

Arthur