Genetic mutations in CRPC

After 3 years on xtandi, It is no longer working as evidenced by my psa doubling in 4 months, though scans are just slightly increased. My Oncologist suggest having some of my soft tissue mets biopsied for possible mutations including Braaca 1 and 2 and several others with the 33% chance that I have one of these mutations, and if I do there is near a 100% chance to have an excellent response to the new drug Olaparib, if not it will be q21 taxotere for me. Not a bad run after 10 years 3 months diagnosed with stage 4 high Gleason PC and given a year , I will be starting one of these two therapies. Here is the abstract.


20 Replies

  • I wish you the best! Let us know your progress.

  • Hopeful and prayerful for your next chapter to go even better Dan.

  • Where are you going for the mutation tests? I am 17 years out with Stage IV and high gleason scores. I am on Xtandi and hormone treatment now. Headed to Duke Onco today for my PSA test . It has ben undetectable for 2 years. Every time my cancer returns there are new treatments that combat the flare up and I am good for a few more years.

  • It depends on where you are being treated some facilities have their own labs. Foundation One is a company that provides genetic testing. Check out the Foundation One website and speak to you oncologist about the test.

    Bill Manning

  • I am getting a laproscopic biopsy at my local Hospital, but they will be sending the slides to foundation one as that is who Dana Farber used when they did the studies

  • Hi Dan

    Yes you should have this done. There are several genetic anomalies that may respond to a PARB inhibitor like Olaparib it it not just limited to BRCA 1 or 2.

    They will do a cheek swab test and a test on a sample from you tumors.

    Genetic anomalies come in two basic flavors. The first is called germline and these are inherited these show up in the cheek sample.

    Somatic mutations are developed within the cancer cells only.

    If you do have germline BRCA and have children it is important information for them to have since people who have BRCA mutations have an increased risk to develop certain types of cancer.

    Bill Manning

  • Thanks Bill I was not aware of the germline swabs from the cheek, I will have to make sure they do this, Thanks


  • Dan,

    I was diagnosed with mPCa 4 years ago. I was on Xtandi for 35 cycles (28 day cycles) until this July. My PSA started increasing at a 4 months doubling rate a year ago. PSA now at 1.2. Initial diagnosis was Stage 4 with bone mets, no soft tissue mets, Gleason 9 in 6 (all on same side) of 12 core samples. I now have some new bone nets, no soft tissue. Just had a bone biopsy last week and some of the samples will be done in-house and some sent outside to Foundation One. My 23andme DNA test showed minimal BRAC risk, but plenty of other high risk areas, namely 17q24.3, TCF2 and 8p21.2. I hope to have a new treatment plan in a month or two. Wish you the best.

  • there are several other mutations that olaparib will work with, some are listed in the abstract I posted with post and yes foundation one is where they want the biopsy sent to. Are you Doctoring in Boston?

  • Yes, Dana Farber. We discussed olaparib at my last visit, along with other options. I want to get Provenge and possibly Radium 223 besides whatever the biopsy results show. Also, a lot has developed in the genetic analysis field since I last had my 23and me DNA analysis. As you probably know, 23and me does not provide this type of info any more.

  • BB66 I too am at Dana and I believe it was their research, I am confused what you mean by 23 and me, but I assume it was genetic testing from the past, thanks for info and lets keep in touch

  • 23andme is a company that did low level DNA testing. They used to provide a fair DNA test based on a cheek swab for $99. About 3 years ago, the FDA shut them down from providing this detailed info, without appropriate counseling. Now they just provide data about your ancestry (price is now $199). You can check their website at

  • My foundation one came back ..olaparib but I am presently on radium 223 ...second injection next week

  • Super Glad to hear that , nice to have something in the back pocket, which genetic mutation did you have?

  • Dan,

    Olaparnib has been effective for many men with the BRACA mutation. However, you could also go first to the chemo and then to the inhibitor. There is NO evidaence which might be the best clinical order. The chemo can be started immediately which could help control the 4 month doubling time.


  • Thanks Joel, The only problem is I have to have a laproscopic biopsy to get a sample and they do not want to do that while on chemo, so I will get that done and begin chemo in 3 weeks

  • Why cant they profile the tissue they already have?


  • Hi Dan, how long were you just on lupron and casodex before casodex stopped working?

  • Hi Anya ,Doc Myers put me on triple dose casodex which is high dose and is not often used, It caused rapid increase in my liver function test to 3 times upper limit of Normal, but it did drop the psa at the time, from there Dr OH switched me to estradiol patches to let the liver recover, I had an immediate response with my Zolodex and climera estradiol patches. Zolodex is similar to Lupron,but is given in premixed implant and not a shot in the ass. When my liver numbers recovered , he switched me to another antiandrogen called Nalutamide and that worked for about 2 years before I switched to Ketoconazole, which was before zytiga and xtandi, so we used that

  • Thanks for the quick reply Dan. We started with Lupron, casodex, and chemo. Once the chemo was over the psa went from 1.6 to 6.4 in about 1-2 months and the doctor thinks its the casodex, which is a lot earlier than we all expected. He gave him the choice of xtandi and zytiga but my dad is very worried about the side effects since he's already felt a lot of changes. At the moment, we are waiting for an MRI approval bc he hasn't had one since before treatment started.

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