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Brca Testing For Prostate Cancer

Prostate Cancer: Who To Test

BRCA Testing and Prostate Cancer Treatment Decisions | Ask a Prostate Expert, Mark Scholz, MD

Current guidelines for germline genetic testing tend to be complex and focus on men with prostate cancer. The NCCN Guidelines recommend germline genetic testing for patients with prostate cancer who satisfy additional criteria such as Ashkenazi Jewish ancestry, family history of cancer and/or based on characteristics of the prostate cancer, such as grade, stage, histology and the presence of metastatic disease. A man with a likelihood 2.55% of carrying a pathogenic BRCA1/2 variant is also eligible for testing. The likelihood of detecting a germline pathogenic variant in men with prostate cancer are presented by gene and by study in Table . All genes listed in Table are considered to be actionable hereditary cancer predisposition genes, but not all genes pose similar risk for prostate cancer or for more aggressive disease. The genes which are believed to have the greatest impact in terms of risk are highlighted in Table . HOXB13 is not included in many of these studies but is associated with prostate cancer in European populations.

Table 2 The prevalence of mutations by various at risk groups.

What About Early Prostate Cancer Screenings

If you’re aged 55 to 69, the U.S. Preventive Services Task Force suggests you talk to your doctor about prostate cancer screening. But if you have a BRCA1 or BRCA2 mutation, guidelines from the National Comprehensive Cancer Network guidelines recommend you think about prostate screenings by age 40.

Most people with prostate cancer live a long time. But the disease can be cured if you catch it before it spreads to other parts of your body.

Your doctor can check for signs of prostate cancer before you have symptoms. That usually includes a prostate-specific antigen blood test. Your prostate makes more PSA when you have prostate cancer. But other health problems can raise your PSA, including an infected or enlarged prostate.

Your doctor will go over the pros and cons of early PSA testing. Theyâll consider your overall health and any other risk factors.

According to the USPSTF, higher-risk groups include the following:

  • Ages 55 or older
  • Non-Hispanic Black people
  • Those with a family history of prostate cancer

Risks of testing outweigh the benefits of screening for prostate cancer in the elderly , those who have major health problems, or those who expect to live less than 10 years.

Talk to your doctor about prostate cancer screenings if youâre in the gender-diverse community. Thereâs some evidence that transgender women who take gender-affirming hormone therapy have a lower risk of prostate cancer, but we need more research in this area.

Genetic Counseling And Testing

Men should consider genetic counseling and testing for BRCA1 or BRCA2 mutations if:

  • They have been diagnosed with male breast cancer
  • There is a known history of a BRCA mutation in the family
  • There is a known history of male breast cancer, prostate or pancreatic cancer in the family
  • There is a history of early breast cancer and/or a history of ovarian cancer in close female relatives
  • The family is of Ashkenazi Jewish ancestry

If you are considering genetic testing, it is important to consult with a genetic counselor. Find a genetic counselor in your area or via telehealth. To help your healthcare provider assess your individual risk, family history should be collected from blood relatives on both your mother and fathers sides of the family. This includes your first degree relatives , second degree relatives , and third degree relatives . It is important to remember that men can inherit BRCA mutations from their mothers, so while collecting information about female breast and ovarian cancer may not seem related to male cancer risk, it is essential in the case of BRCA mutations.

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Heritable Risks Of Prostate Cancer

Germline testing in men with prostate cancer is being performed more often since an important number of prostate cancer cases have a heritable component.1,2 Germline mutations in DNA repair genes, such as BRCA1/2, contribute to hereditary prostate cancer risk and are present in up to 11.8% of men with metastatic prostate cancer,3 compared with 4.6% among men with localized prostate cancer and 2.7% in persons without a known cancer diagnosis.3,4

Components Of Germline Testing Counseling

BRCA Gene and Prostate Cancer

Oncologists who choose to perform germline testing need to be comfortable with several aspects of genetic counseling and to remain current on the ethics of informed consent and posttest counseling for germline testing . The 2019 Philadelphia Prostate Cancer Consensus Conference suggests that optimal pretest consent should include discussion of the purpose of testing, types of possible results , the possibility of identifying hereditary cancer syndrome and/or other cancer risks, testings potential cost, the importance of cascade family testing, and the Genetic Information Nondiscrimination Act law.12 The GINA law protects against discrimination based on genetics in employment and health insurance however, it is not applicable to life insurance, long-term care disability insurance, Indian Health services, and patients enrolled into federal employee, Veterans Administration, and US military health benefit plans.23,24 These gaps in protection by GINA law are important to discuss with patients, who may need to consider them before proceeding with the germline testing. Providers should also consider discussing the different panels available for testing, the privacy of genetic tests, and genetic laboratories policies related to sharing and selling of data.12

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Prostate Cancer And The Role Of Brca

Mayfair Oct 21, 2020

After lung cancer, prostate cancer is the second most common cancer diagnosis for men. According to the Canadian Cancer Society, prostate cancer accounts for one-fifth, or 20 percent, of all new cancer cases in men. On the other hand the five-year net survival rate is high for prostate cancer at 93 percent.

The Canadian Cancer Society attributes the declining mortality rate for prostate cancers to success in prevention, screening, and treatment. A key component to any prevention strategy is increased awareness and education about prostate cancer.

In Canada, one in nine men will be diagnosed with prostate cancer in their lifetime. When detected early, prostate cancer is one of the most successfully treated types of cancer, so its important to be aware of your risk factors and get checked. Screening for prostate cancer usually involves a blood test, called a prostate-specific antigen test to measure PSA levels in the blood. It takes around 10 minutes, and would need to be ordered by your health care practitioner.

While high PSA levels could indicate prostate cancer, they could also be caused by other factors. Your doctor will likely discuss the risks and benefits of this test with you, as well as other potential risk factors for developing prostate cancer.

Aua : Genetic Testing In Advanced Prostate Cancer

BRCABRCA1/2BRCA2

  • Genomic profiling: tissue-based biopsies and proprietary molecular signatures
  • Used for treatment and management decisions
  • Genomic tumor sequencing: tissue or liquid biopsy, with extensive testing of tumor-specific mutations
  • Used for direct targeted therapies and assessing clinical trial eligibility
  • Inherited cancer risk testing: identifying inherited mutations by buccal/blood testing and assessing for increased cancer risk
  • Used for cancer screening and prevention, genetic testing in close relatives, and informing treatment decisions and clinical trial eligibility
  • BRCA-2BRCA-2

    • Pathogenic or likely pathogenic mutation these patients should be referred for genetic counseling after a detailed review of their family history. Additionally, it may be recommended that testing be performed on family members for cascade testing
    • Benign or likely benign no pathogenic mutations definitively identified
    • Variant of unknown significance these patients can be considered a negative test but requires follow-up and ongoing review for newly identified mutations. GenBank maintains a central repository of reported genes

    BRCA

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    How Do Brca Genes Affect Prostate Cancer Risk

    Around 10% of all prostate cancers are linked to inherited gene changes. These are called hereditary cancers. The BRCA genes boost your odds of developing hereditary prostate cancer, especially the BRCA2 gene.

    If you have a BRCA2 mutation, most studies show you may have around a 20% to 40% chance of developing prostate cancer over your lifetime. For some people, research shows the odds may be as high as 60%.

    To put that in perspective, someone without this mutation has about a 16% chance of developing prostate cancer at some point in their life.

    Cancer affects everyone in a different way. And many people who inherit a BRCA2 mutation wonât ever develop prostate cancer. But compared with people without this gene change, studies show that those with the variant are more likely to:

    • Have an aggressive form of prostate cancer
    • Develop prostate cancer before age 65
    • Have cancer that comes back after treatment
    • Die for reasons related to prostate cancer

    Thereâs some evidence that people with a BRCA2 mutation who have advanced, or metastatic, disease may respond better to certain prostate cancer treatments. That includes PARP Inhibitors. But we need more research to know which treatment works best for this group.

    If you have a BRCA1 mutation, your lifetime odds of prostate cancer may not go up very much or at all.

    What Is The Value Of Screening For Prostate Cancer Among Men At High Risk

    Metastatic Prostate Cancer: Testing for BRCA Mutations

    The value of screening for prostate cancer in the general population is controversial. Three large randomized controlled trials of PSA screening and mortality produced mixed results. The European ERSPC study and the Gotenberg study found a 2030% and 52% reduction in prostate cancer mortality respectively,, whereas the US PLCO trial showed no mortality difference between the treatment and control arms. The US Preventative Services Task Force recommends a discussion of the risks and benefits of PSA screening in men aged between 55 and 69 . The NCCN recommends that men with a germline mutation that increases the risk for prostate cancer consider annual PSA screening from age 40 . The NCCN also recommends annual screening in men with a family history and men of African descent from age 40, but notes that the evidence does not show a mortality benefit associated with earlier screening,. The American Cancer Society recommends starting a discussion about screening at the age of 40 for men at high risk, including those with more than one first-degree relative who had prostate cancer at an early age .

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    Genetic Testing For Prostate Cancer

    Thanks to research funded by the Prostate Cancer Foundation, we now know that some prostate cancers are caused by changes in your genes. 5%-10% of all cancers are hereditary, meaning that certain cancer-causing gene changes are passed down from mothers and fathers to sons and daughters. Another 10%-20% of all cancers are familial, meaning that a type of cancer occurs in multiple family members, but is not directly related to specific gene changes.

    Genes are made of DNA, which is the master instruction manual that tells every cell in the body which proteins to make essentially, the information that each cell needs to do its job. A genetic mutation is a change in part of the normal DNA that makes up a gene. Some mutations are hereditary, meaning that they are passed down from one family member to another. Mutations can also be caused after birth by various lifestyle and environmental factors, such as smoking or the UV rays from the sun.

    Genetic mutations can be passed down from father to son, father to daughter, mother to son, or mother to daughter. We now know that some of the same gene mutations that cause prostate cancer can also cause other forms of cancer and vice versa. Therefore, it can be important to consider genetic testing if you have a history of cancer in your family, even if its not prostate cancer. This is referred to as genetic testing for an inherited mutation or genetic testing for inherited cancer risk.

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    Whats The Brca Gene Testing Procedure Like

    BRCA gene testing begins by meeting a doctor or counselor for genetic counseling. Genetic counseling is a process by which your medical and family history is reviewed to determine if genetic testing is the right choice for you.

    If your doctor or counselor recommends the BRCA gene test, youll be scheduled for a blood or saliva test. While blood testing is the most common method for BRCA testing, saliva testing is a less invasive option.

    Once your test has been performed, you can generally expect to receive test results within 2 to 4 weeks.

    Coverage of BRCA gene testing ultimately depends on your individual medical insurance plan.

    According a 2011 case study , most private insurance companies do cover BRCA gene testing for individuals who meet the eligibility criteria. Eligibility criteria varies from plan to plan, but usually includes individuals who are considered high-risk for cancer.

    However, BRCA coverage does not seem to be as common for individuals enrolled in public insurance plans, such as Medicare and Medicaid.

    Without insurance, BRCA testing can range from roughly

    Increased Risk Of Prostate Cancer In Men With Brca2 Gene Fault

    What Men Should Know About the BRCA Gene

    by Cancer Research UK

    Men with the BRCA2 gene fault have an increased risk of prostate cancer and could benefit from PSA testing to help detect the disease earlier, according to researchers funded by Cancer Research UK.

    Previous studies have shown that PSA is not a suitable test for screening for prostate cancer in the general population, and this remains the case. There are limitations to the PSA testincluding false positives, false negatives and overdiagnosis.

    But new research found that PSA tests were more likely to pick out more serious forms of prostate cancer in men who carry the BRCA2 gene fault than in non-carrierssuggesting these men could benefit from regular PSA testing.

    In the study published today in European Urology, researchers at The Institute of Cancer Research, London, looked at around 1400 men and compared those who dont carry the BRCA2 gene fault with those who do.

    Men were offered a yearly PSA test and depending on the result, they were either offered a biopsy to confirm their disease and treated if needed or asked to come back the following year.

    The researchers found that men who carry the BRCA2 gene fault were almost twice as likely to be diagnosed with prostate cancer than non-carriers.

    They also found that carriers were diagnosed at a younger agean average of 61 compared with 64 in non-carriers.

    And receiving a false positive result can lead to unnecessary worry and unnecessary biopsies.

    Explore further

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    Prostate Cancer Screening With A Brca Mutation

    This is part of an ongoing series featuring interviews with physicians on topics related to hereditary cancer. This article was written by Kara Maxwell, MD, PhD. Dr. Maxwell is a physician scientist with the Basser Center and the Abramson Cancer Center at the University of Pennsylvania. Her areas of expertise are in cancer genetics, specifically in hereditary cancer syndromes.

    In 2019, we hope that no man should die from prostate cancer. Its a treatable disease with early screening and detection, but who to screen remains controversial. The United States Preventative Task Force no longer recommends routine prostate-specific antigen screening for all men and it is instead an individualized decision between a man and his healthcare provider. This is not unreasonable, given that many men may die with prostate cancer, not of prostate cancer, and there are significant concerns about complications from prostate cancer treatment. Therefore it is of paramount importance that we are screening and treating the men that need it most.

    Screenings should occur yearly. Most men should recognize that they are going to have fluctuations in their PSA and that PSA screening, at some point, should wind up having to be more frequent if theyre following a trend upwards. In addition, screenings should not just be limited to a PSA, but should also include a digital rectal exam from a urologist.

    Resistance Mechanisms To Parp Inhibitors

    There are a few mechanisms that cause PARP inhibitors resistance. Firstly, tumor cells can perform mutational reversion of BRCA1/2, which causes restoration of the HR DNA repair pathway . Secondly, the stabilization of stalled forks in the cells also leads to resistance this is achieved through the loss of fork degradation pathways . A third mechanism is through the mutation of PARP1 in tumor cells preventing trapping and cytotoxicity to these cells . Lastly, tumor cells can upregulate the permeability glycoprotein efflux pumps, causing reduction of PARP inhibitors concentration intracellularly and decreased efficacy . The summary of the mechanisms of resistance to PARP inhibitors is presented in Figure 2.

    Mechanisms of resistance to PARP inhibitors. Cancer cells develop different resistance mechanisms that pose a significant obstacle to the prolonged use of PARPi. Several proposed molecular mechanisms of PARPi resistance, including restoration of HR capacity, stabilization of replication forks, diminished trapping of PARP-1, and P-gp-mediated drug efflux, are highlighted in four sections.

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    Treatment Implications Of Germline Testing

    Advanced disease

    PARPi. Patients with DNA repair mutations have higher response rates to PARPi and platinum chemotherapy.31,32 In 2020, two PARPi received FDA approval for treatment of mCRPC with germline or somatic DNA damage repair gene mutations. Rucaparib was approved based on the phase 2 TRITON2 study it reported a 51% radiographic response rate among men with mCRPC and BRCA1/2 alterations.33 The benefit for men with non-BRCA DNA repair mutations was less clear, and rucaparib is currently approved only for carriers of BRCA1/2 mutations. 33-35 The olaparib label includes a larger number of mutated genes eligible for treatment , based on results of the phase 3 ProFOUND study . ProFOUND compared olaparib with enzalutamide or abiraterone and showed improved radiographic progression-free survival with olaparib. 36 Several other ongoing studies are evaluating the efficiency of PARPi monotherapy and combined therapies in mCRPC. Table 3 summarizes study results reporting response rates to PARPi in prostate cancer. 37

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