What Is a Prostate Cancer Genetic Mutation?

What Is a Prostate Cancer Genetic Mutation? from Patient Empowerment Network on Vimeo.

 What is a prostate cancer genetic mutation? Dr. Himisha Beltran defines genetic mutations, where they may occur, and how identification of mutations can assist in prostate cancer detection and care.

Dr. Himisha Beltran is Director of Translational Research in the Department of Medical Oncology at Dana-Farber Cancer Institute. Learn more about Dr. Beltran, here.

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Transcript:

Dr. Beltran:

So, genetic mutation refers to changes in the DNA sequence of an individual or their cancer. And so, we know that normal individuals have variations in their inherited or normal DNA that drive diversity. And some of these changes actually in your inherited DNA can predispose to future development of cancer. So, those are important to identify as those are mutations that may help us guide early detection and screening strategies for people at high risk for cancer.

There are also genetic mutations in cancers themselves. And each cancer type is characterized by different patterns of mutations that can sometimes help us in the clinic figure out, where did a cancer come from? Did it come from the prostate, or did it come from somewhere else? Some of these mutations in the cancer can also be targeted with drugs. And there are drug approaches that are developed that specifically target an individual’s mutation in their cancer. And every individual, even within prostate cancer, may be different. And so, this is something that we’re commonly testing for in the cancer itself by doing DNA sequencing to look for letter changes in the DNA.

What Is a Prostate Cancer Biomarker?

What Is a Prostate Cancer Biomarker? from Patient Empowerment Network on Vimeo.

What is a prostate cancer biomarker exactly? Dr. Himisha Beltran defines biomarkers and breaks down three types of biomarkers that help guide optimal care for prostate cancer patients.

Dr. Himisha Beltran is Director of Translational Research in the Department of Medical Oncology at Dana-Farber Cancer Institute. Learn more about Dr. Beltran, here.

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Transcript:

Dr. Beltran:

So, the word, ‘biomarker’ is a term that we often use that refers to a set of information or a test that provides insights into a particular diseased state. And in prostate cancer, there are several different types of biomarkers that we use. There are diagnostic, prognostic, and predictive biomarkers. And each of them provide different sets of information. A diagnostic biomarker is a test that improves the diagnosis of prostate cancer, and one that we are very familiar with is PSA test. This is a test that’s commonly done that may lead a suspicion of cancer. That leads to an additional work-up for prostate cancer. And there are other tests, urine, blood, and tissue-based, that can improve the detection of prostate cancer as well as specific types of prostate cancer.

Then there are prognostic biomarkers. A prognostic biomarker is a biomarker that provides insight into how indolent or aggressive a cancer is. And this can inform treatment decisions for newly diagnosed patients in trying to consider whether you should do active surveillance or get local therapy. In the more advanced disease setting, a prognostic biomarker can help us think about treatment intensification strategies for patients that are predicted to not respond as well to traditional approaches. And these are often molecular tests.

And then there are predictive biomarkers, which in opinion, are quite informative in trying to make a prediction as to how likely will respond to a specific treatment. And this is a really emerging field. And in an advanced prostate cancer, one example of a predictive biomarker is a mutation in a gene called BRCA2, which can identify patients more likely to respond to a PARP inhibitor versus those that do not. That’s just one example of how we may be able to use molecular features of a cancer to provide insights into what therapy that patient might benefit from most.

There are no perfect biomarkers. All of these types of biomarkers are just tools that we use to help guide treatment decisions at different stages of prostate cancer.

Prostate Cancer Treatment Decisions: How Do Genetic Test Results Impact Your Options?

Prostate Cancer Treatment Decisions: How Do Genetic Test Results Impact Your Options? from Patient Empowerment Network on Vimeo.

How do genetic test results impact prostate cancer treatment options? Dr. Nima Sharifi explains BRCA mutations, germline genes, and somatic mutations—and discusses when treatment with PARP inhibitors may be appropriate.

Dr. Nima Sharifi is Director of the Genitourinary (GU) Malignancies Research Center at the Cleveland Clinic. Learn more here.

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Transcript:

Dr. Sharifi:        

There are several types of mutations that occur in prostate cancer. We know about a lot of them. We’re beginning to understand the function of many of them, and the role of just a few of them has become a bit clearer in treatment of prostate cancer. So, the one that I think has the clearest implications is something called BRCA mutations.

So, you can get mutations in genes that regulate DNA damage. This can occur in either inherited genes, or these are mutations that can occur in the cancer itself. And this will allow for tumors to become the developed – actually, greater DNA damage. The implications of using this information, genetic testing for these BRCA mutations, are actually several. One is that it may – if it comes in through the germline, then it tells us something about the hereditary or familial component of it.

So, that has implications not only for the patient but also potentially family members. And then the second set of implications has to do with treatment, and specifically treatment that in more advanced cases where there are now two FDA-approved agents that are used specifically for patients who have mutations in these genes.

And we’re still learning a lot about what these genes mean, or mutations of these genes mean for patients in their clinical course. And we’re learning much more information about other mutations which may occur in prostate cancer as well.

So, we should draw a distinction between two different types of genes. One is germline. Germline has to do with the DNA or the genes that you inherit from your parents. And the second category is somatic mutations, or somatic genetics. And this, specifically, has to do with mutations that occur in the cancer cell itself, but that are not inherited from one’s parents.

It’s a very active area of research. So, again, for the vast majority of mutations that we recognize in prostate cancer, we don’t use that to make clinical decisions. There are a few, such as the DNA damage repair genes or BRCA genes – which tell us something about the potential for a more aggressive disease course or a more aggressive disease – and also the potential appropriateness of using agents called PARP inhibitors, which seem to specifically work in patients who have mutations in the BRCA family of genes.

So, in terms of the treatment options, the major genetic tests that allow us to figure out whether systemic or drug treatment option is appropriate or not, is in DNA damage repair genes such as BRCA.

So, for example, in the case of metastatic disease that’s resistant to hormonal therapy and has already been treated with other therapies, if there is a mutation in BRCA or one of the closely related gene members, then use of a drug called a PARP inhibitor may be appropriate, and that could benefit patients.

How Can You Insist on Better Prostate Cancer Care?

How Can You Insist on Better Prostate Cancer Care? from Patient Empowerment Network on Vimeo

How can prostate cancer patients access the best care in an evolving treatment landscape? Prostate cancer survivor Jim Schraidt shares his advice for staying up-to-date about treatment developments and for accessing support and resources

Jim Schraidt is a prostate cancer survivor and Chairman of the Board of Directors for Us TOO International. Learn more about Jim Schraidt here.

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Newly Diagnosed with Prostate Cancer? Consider These Key Steps

 


Transcript:

Jim Schraidt:              

The really great news is that sort of across the board, from early stage disease through metastatic prostate cancer patients, there are advances that are occurring very rapidly at this point, so rapidly that practitioners have difficulty keeping up with them.

And, honestly, those of us who do some patients support likewise have difficulty keeping up with them. I think, once again, these support groups can serve a useful function in that you have specific questions, you hear about it, you bring together a group of individuals, and somebody in that group may know something about it.

And they can tell you, they can give you information, or they can give you direct Internet links where you can find more information. The other source of information is some of the Us TOO publications, our monthly hot sheet, as well as the website.

There are a couple other websites that I personally regard as excellent. The first would be the Prostate Cancer Foundation. The second would be Prostate Cancer Research Institute. And then finally, ZERO. So, I think if you attend a support group, and talk to other guys, and look at some of these websites, I think that’s a very good starting point for research and trying to get the best and most up-to-date information possible.

There’s a lot of progress being made across the disease spectrum, and it’s very exciting. I mean, for many years, all we had was surgery, radiation, and hormone therapy. But new things are coming online all the time. There are immunotherapies that are frequently genetically based. And there’s new knowledge about the disease itself and making active surveillance available to more patients.

And this is extremely critical because many men can go on with prostate cancer, with low-grade disease, really for their entire lives, and avoid the side effects of treatment.

And even if they don’t, if they delay definitive treatment for a period of years, there may be something new that comes down the pike that is both effective and has a better side-effect profile. This is the kind of research that is a part of what Prostate Cancer Foundation is funding.

So, there’s a lot out there. There’s a lot that’s happening. And I think that should give encouragement to prostate cancer patients. In terms of somebody who is later in the process and having difficulty coping with side effects or disease progression, I think the encouragement is that there are people out there that you can talk to about it, that you’re really not alone, and there are people out there that are anxious to help you, to hear from you, and provide assistance.

For those of us who have been at it a while, we find that helping others enhances our own healing. And so, don’t be reticent about asking for help. Because it’s out there, and it can really make a difference.

The Link Between Prostate Cancer and Inherited Mutations

The Link Between Prostate Cancer and Inherited Mutations from Patient Empowerment Network on Vimeo

How can inherited genetic mutations affect the course of your disease? Dr. Sumit Subudhi explains the link between inherited mutations and prostate cancer and how these mutations affect disease progression in patients with prostate cancer.

Dr. Sumit Subudhi is a Medical Oncologist at The University of Texas MD Anderson Cancer Center.

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Transcript:

Katherine:                   

Dr. Subudhi, what is the link between inherited mutations and prostate cancer?

Dr. Subudhi:                 

Yeah, so in approximately 10% to 15% of patients with prostate cancer, they have an inheritable cause for their cancer. And so, this predisposes them to not just having prostate cancer, but potentially to other cancers, but also their family members.

In regards to the inheritable causes, the BRCA mutations – BRCA2 and BRCA1 – are very common. In fact, BRCA2 is more common than prostate cancer than BRCA1. In addition, there’s CHEK2 and ATM which are common inheritable mutations. And the other ones are the mismatch repair genes. Again, all these play an important role in repairing DNA. So, if you’re mutated in these genes, then your ability to repair DNA has been significantly diminished, and you’re more likely to gain more mutations.

Katherine:                   

How do these mutations affect disease progression?

Dr. Subudhi:                 

Yeah. So, what they can do is they can lead to mutations that make the cancer grow more. And there’s two ways to do it. You can have a mutation in what we call an oncogene, a gene that when it’s active, it’s going to just promote the cancer.

And then we have other genes called tumor suppressor genes. Their normal function is to prevent the cancer from growing. But if the tumor suppressor gene gets mutated so it’s no longer functional, then the cancer can then take off, because it’s no longer suppressed. So, those are how these genes can actually affect the prostate cancer.

If you have either an inheritable mutation in these genes or a somatic mutation, then there’s a chance that the PARP inhibitors could actually work for you. And the PARP inhibitors, they actually target cancers where there’s a defect in the DNA repair pathway.

Now, there’s one thing that I want to point out that a lot of people sort of are missing, and it’s not a subtle point. Not all inheritable mutations are made the same – or even somatic mutations. Meaning, what we’re learning is the PARP inhibitors seem to be more active with the “Braca,” or BRCA, mutations and the ATM mutations. Whereas, they’re less active with other types of DNA repair mutations. So, the point is not all mutations are made the same.

Prostate Cancer Testing: What Tests Should You Advocate For?

Prostate Cancer Testing: What Tests Should You Advocate For? from Patient Empowerment Network on Vimeo.

Genetic testing results can influence a prostate cancer patient’s treatment options and provide a more in-depth understanding into their disease. Dr. Sumit Subudhi reviews specific tests that prostate cancer patients should advocate for.

Dr. Sumit Subudhi is a Medical Oncologist at The University of Texas MD Anderson Cancer Center.

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Transcript:

Katherine:                   

What is the role of genetic testing in prostate cancer?

Dr. Subudhi:                 

That’s a great question, because this is something that wasn’t really available when I was training and understanding prostate cancer. But over the last few years, this has actually hit the mainstream, and it’s very important. And I see it having three roles. The first role is whether or not you can receive a certain type of targeted therapy or systemic therapy known as PARP inhibitors. So, if your genetic test is positive for certain markers – that I think we’ll cover later – then it can help give you more treatment options. The second is that generate testing can give you also risk of other cancers besides prostate cancer. For example, if you have the BRCA mutation, you’re 15% to 20% more likely to get breast cancer in men.

The third is that because the genetic testing is looking for inheritable mutations in your genes, that means you can pass it along to your kids. And this could have a tremendous impact on the screening strategies your children want to use in the future.

Katherine:                   

Would you mind going into that a little bit?

Dr. Subudhi:                 

Yeah.

Katherine:                   

For instance, my ex-husband had early prostate cancer. My 22-year-old son is worried now about also getting prostate cancer. His grandfather had prostate cancer.

Dr. Subudhi:                 

Yeah, great question. So, it’s not just about prostate cancer. So, prostate cancer, genetically, is linked to other cancers, as well.

So, in your case, you’re turning by your son. But if you have daughters or any female members in the family, consideration needs to be given to breast and ovarian cancer. And for both men and women, we also have to think about melanoma and pancreatic cancer. So, it’s not just prostate cancer that we’re thinking about when you have these genetic risks. And that’s very important, because each of these different cancers can have different screening modalities.

Katherine:                   

Oh. Well, how is the testing administered then?

Dr. Subudhi:                 

The testing is actually a blood test, so very simple.

Katherine:                   

Have there been any major advances in testing?

Dr. Subudhi:                 

Yeah, so when we’re talking about the inheritable testing, that’s just a simple blood test. And the reason why it can be done simply through the blood is because every cell in your body has it. So, when they collect the blood, they can just take any cell from there and do genetic analysis. And if that gene is mutated or missing, it will be captured.

Now, there’s another type of testing where they test your tumor tissue itself – so, your cancer tissue – whether you got it by biopsy or surgically removed. And so, that’s a different type of testing. That’s looking for what we call somatic mutations. These are not inherited mutations. These are mutations that are specific for your prostate cancer. Again, in contrast, the inheritable mutations are in every cell in your body – not just your prostate cancer cells, but every cell in your body. And the somatic, it’s just in your prostate tissue itself.

And so, sometimes with prostate cancer, it’s difficult to get the tissue. And what’s happened more recently – and to answer your question – is that the advances have been in what we call liquid biopsies, where they are able to use your blood and get the DNA from the tumors and actually genetically test the cancers that way. And so, that’s where the future is going.

Katherine:                   

Oh, that’s amazing. Are there specific tests that patients should ask their doctor for following the diagnosis?

Dr. Subudhi:                 

Yeah. So, if inpatients with high risk or metastatic prostate cancer, they should definitely be considering tests to see if they have mutations in what we call the DNA damage repair pathway or homologous recombination DNA pathway. And I know they’re fancy terms. What these genes are, they’re genes that help the body repair their DNA, and DNA is very important. And so, when there’s defects in the DNA repair pathway, then mutations occur. And these mutations can actually help the cancer grow.

 Now what’s happening is that what they’re looking for in these genetic tests – whether it’s the inheritable test or the somatic mutation test that’s looking just within the tumor itself – they’re looking to see if there’s any DNA damage machinery that’s defective. And if it is, then you’re more likely to benefit from PARP inhibitors, which are oral drugs that specifically target the DNA repair pathway.

Prostate Cancer Staging: What Patients Should Know

Prostate Cancer Staging: What Patients Should Know from Patient Empowerment Network on Vimeo

Dr. Sumit Subudhi provides a brief explanation of the stages of prostate cancer, the role of staging in determining a prostate cancer patient’s treatment path, and how patients can advocate for a precise diagnosis.

Dr. Sumit Subudhi is a Medical Oncologist at The University of Texas MD Anderson Cancer Center.

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Transcript:

Katherine:                   

Well, Dr. Subudhi, I’d like you to begin with a brief explanation of the stages of prostate cancer.

Dr. Subudhi:

We use stages, and there’s four – Stage I, II, III, and IV. And we use it to help us determine what treatments the patients need for their prostate cancer. In general, Stage I is localized prostate cancer, and it’s localized only to the prostate. And when we do a digital rectal exam, we cannot feel or palpate the prostate.

And the treatment for Stage I prostate cancer is either active surveillance, where you’re not trying to cure the cancer, you’re just actively watching it, and you’re using a PSA imaging studies, prostate biopsies, and digital rectal exams at regular intervals to follow the patients. But other patients with Stage I prostate cancer can actually get definitive treatment for curative intent with radiation therapy or surgery. Stage 2 prostate cancer is also localized, but on physical exam, we can actually palpate or feel the prostate cancer. And this also can receive definitive treatment for the prostate to cure it, and that, also, you can use radiation therapy and surgery.

Stage III is what I consider locally advance. This is where the prostate cancer is now starting to leave the prostate. And it still can be cured by radiation and surgery, but most likely needs a multidisciplinary approach, where you might need both or maybe even in addition of a systemic therapy. Stage IV is the last stage that I’ll talk about, and it has distant metastases. And here we’re not looking for a curative approach; we’re actually looking for palliation, which means that we’re trying to treat the prostate cancer as a chronic disease.

Katherine:

I understand that there are many types of prostate cancer that have been identified. How can patients advocate for a precise diagnosis?

Dr. Subudhi:

Yes, you’re absolutely right. There are many types. So, we have historically used histological classification. And when I say histological, that means when we look at the cancer under the microscope, we can look at the different structures within the prostate cancer and classify them.

And there are multiple types such as adenocarcinoma, neuroendocrine, small-cell, mucinous, etc. But more recently, with the advances in genetic and molecular testing, we now can look at the genes inside the prostate cancer, and that has also helped us better classify the cancer. Now many of these types of approaches are best done at major cancer centers, where they have experienced pathologists who actually evaluate both histologically and molecularly the cancer.

So, I recommend to my patients, or family and friends, that have been diagnosed with prostate cancer that they don’t necessarily have to go to the major cancer centers. They can have their local doctor send the tissue from the biopsy to the advanced cancer centers to get a second opinion.