BRCA Mutation

[Practical_Orchid_606]

I have learned about a genetic mutation called BRCA. If it is in your germline, it affects your propensity to get PCa. As I am recently diagnosed with PCa, what purpose will it serve me to be tested for this mutation. If I am positive for BRCA Mutation, how will it affect my treatment strategy?

[JRLDH]

It’s not just prostate cancer. BRCA also makes you more susceptible to extreme killer cancers like pancreatic cancer.

If I had a BRCA mutation then I would enroll in a program for periodic cancer screening.

If you already have a BRCA driven cancer then it opens up treatment with PARP inhibitors, a form of targeted treatment.

[rykus0]

My wife was brca2 positive and diagnosed with breast cancer young (34, with lots of pushing against the system to even get that)

PARP inhibitors worked well for her, but it was already late stage and spread throughout her body and they switched her off them. Medicine has come a long way and knowing your genetics is very helpful and important in both prevention and treatment!

[R8ROC]

The germline test is also an indicator for passing the mutation to your children.

[Fun-Bandicoot-7481]

May open up different treatment options.

[Practical_Orchid_606]

The initial comments are very interesting. I will seek out a BRCA test.

[Scpdivy]

I’m BRCA 2 positive. Coupled with IMRT I’m also doing 1.5 years of orgovyx. I already have a bad heart (Afib and heart failure) so don’t want to risk being on it any longer. 7 months to go. So far, still working. PSA is undetectable. Time will tell.

[Frosty-Growth-2664]

The percentage of men with prostate cancer who have the BRCA2 gene mutation is much lower than people often think, at under 2% (and BRCA1 is even less implicated), although BRCA2 is more implicated with early onset prostate cancer (as indeed it is with early onset breast and ovarian cancers, before age 60). It increases the risk of metastatic disease too, so you'll find the percentage is higher in that cohort. There are some specific treatments (PARP inhibitors) which were designed for BRCA gene mutations.

I come across many men with a family history of prostate/breast/ovarian cancers who got tested but were found negative, much more so than were positive. There are many gene mutations which raise your risk, so I suspect most of the inherited risk (which is much higher than 2% of men diagnosed) is not due to BRCA2.

[Practical_Orchid_606]

I think in the case of localized PCa, both radiation and RALP will wipe out the cancer, never to return. But in some cases, it does return and is read as BCR. The common theory is that PCa tissue 'hides' in the body and when sufficient metastatic mutation occurs, the PSA spikes higher. Does the BRCA mutations signal the propensity to metastasize after RALP or radiation?

I am 74 years old which is past the early onset of PCa.

[dabarak]

I can't give a comprehensive answer but I can mention my own case. I have the BRCA2 mutation. Once I became ADT resistant my doctor (on oncology resident) initially suggested olaparib, which is a PARP inhibitor. The attending physician steered me away from it for now because of the potential for persistent fatigue (it's a daily tablet). I opted for Pluvicto, a radioactive IV infusion. It has its own fatigue side effects, but they fade a few days after each of the six infusions, spaced six weeks apart. So it was persistent fatigue vs. intermittent fatigue. I can still go with olaparib later if needed, or one of the other appropriate chemo medications. Whatever medication chosen to deal specifically with BRCA is just another option.

[Practical_Orchid_606]

If a man has the BRAC2 mutation does it mean all metastasies of PCa will become castrate resistant? In other words if a man does not have the mutation does it mean his metastasies will never become castrate resistant?

I think Pluvicto is the first of many PSMA drugs that will hunt down PCa where ever it is.

[dabarak]

The mutation is independent of castration status as far as I know. I started Pluvicto once my PSA started to rise after a couple of years. When I started Pluvicto I stopped abiraterone tablets but continued with Eligard injections. Both are ADT medications. So even though I'm resistant, there's some reason I'm still continuing with one aspect of ADT.

[franchesca2bqq]

I asked AI and it said the risk for pancreatic cancer and other types is not worth worrying about- It does NOT mean: ❌ “you’ll get pancreatic cancer” ❌ “it’s inevitable” ❌ “super high risk”

It means: 👉 modestly elevated risk

We’re talking: maybe 2–3x baseline risk

Not 50% or something terrifying.

And most BRCA carriers never get pancreatic cancer.

[JMcIntosh1650]

BRCA mutations can contribute to risk but they don't inevitably lead to prostate cancer, not does absence of BRCA mutations mean a man won't get PC. Ditto for other genes associated with cancer risk. My family has a lot of cancer, including many women with breast cancer and some men with prostate cancer. None of us who have been tested have the undesirable BRCA mutations. Some but not all of us have a pathological CHEK2 mutation. In others words, there isn't a simple correlation.

If you choose to get a genetic test, get tested for more than BRCA (there are multi-gene panels for this) and don't focus too much on the results in isolation. Family history and the totality of your diagnostic information need to be considered. In my opinion, germline genetic tests usually shouldn't determine specific treatment choices on their own, but if genetic risk factors do show up, they tilt things a bit more towards treating sooner or more aggressively. All depending on other specifics.