How Do I Know If I Need To Get Tested
While there is still much we do not know about prostate cancer, certain segments of the population are believed to be at an increased risk for carrying a BRCA1 or BRCA2 mutation. Individuals with a first or second degree relative who has been diagnosed with breast cancer before the age of 50 are thought to be at an increased risk for carrying the gene mutation. Additional risk factors include:
- Having a father or brother with prostate cancer.
- Two first- or second-degree relatives with breast, pancreatic, or prostate cancer.
- People of Ashkenazi Jewish descent.
It is important to remember that you will not necessarily develop prostate cancer even if you fall into one or more of these categories, or even if you test positive for a BRCA mutation.
Currently, there are no preventative treatments for individuals who have a BRCA1 or BRCA2 mutation. However, knowing there is a mutation in the family may prompt your primary care physician to recommend prostate screenings more frequently or at an earlier age.
If a tumor does develop, these additional tests may provide insight into certain vulnerabilities of the cancer and opportunities for specialized, targeted therapies.
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
What You Need To Know About The Prostate Radiation Therapy For Prostate Cancer And Brca2 Gene Causing Radiation Sensitivity
The main purpose of the prostate is to produce semen, a milky fluid that sperm swims in. During puberty, the body produces semen in a large number of cases, including enlarged prostate. This fluid causes the prostate to swell and cause a number of bladder-related symptoms. This is why the prostate is important to the body. It can be caused by many factors, including infection and inflammation.
A enlarged prostate can also cause blockages in the urethra. A blocked urethra can also damage the kidneys. A patient suffering from an enlargement of the prostate may have pain in his lower abdomen and genitals. If pain is present, a digital rectal examination will reveal hard areas. A doctor may prescribe surgery or perform an endoscopic procedure. If the enlarged prostate is not completely removed, it will shrink.
While the size of an enlarged prostate will influence the extent of urinary symptoms, men may experience a range of urinary symptoms. Some men have minimal or no symptoms at all. Some men will have a very enlarged prostate, whereas others will have a mild enlargement. Generally, the symptoms can stabilize over time. Some men may have an enlarged prostate but not notice it. If they have an enlarged colon, their physician can perform a TURP procedure.
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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 You Need To Know About The Prostate Biomarkers Prostate Cancer Palb2 Ntrk Brca1
The main purpose of the prostate is to produce semen, a milky fluid that sperm swims in. During puberty, the body produces semen in a large number of cases, including enlarged prostate. This fluid causes the prostate to swell and cause a number of bladder-related symptoms. This is why the prostate is important to the body. It can be caused by many factors, including infection and inflammation.
A enlarged prostate can also cause blockages in the urethra. A blocked urethra can also damage the kidneys. A patient suffering from an enlargement of the prostate may have pain in his lower abdomen and genitals. If pain is present, a digital rectal examination will reveal hard areas. A doctor may prescribe surgery or perform an endoscopic procedure. If the enlarged prostate is not completely removed, it will shrink.
While the size of an enlarged prostate will influence the extent of urinary symptoms, men may experience a range of urinary symptoms. Some men have minimal or no symptoms at all. Some men will have a very enlarged prostate, whereas others will have a mild enlargement. Generally, the symptoms can stabilize over time. Some men may have an enlarged prostate but not notice it. If they have an enlarged colon, their physician can perform a TURP procedure.
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Side Effects Of Parp Inhibitors
Side effects of these drugs can include nausea, vomiting, diarrhea, fatigue, loss of appetite, low red blood cell counts , constipation, skin rash, abnormal liver blood tests, low blood platelet counts, cough and shortness of breath. Rarely, some people treated with these drugs have developed a blood cancer, such as myelodysplastic syndrome or acute myeloid leukemia. Some men taking olaparib had problems with blood clots in the lungs or legs.
Thank You For Helping To Make Breakthroughs In Treating Prostate Cancer Possible
These results represent a giant leap forward for men with prostate cancer. A leap weve been building towards since 2014, with your support, through research funding and behind-the-scenes work.
With your help were moving from a one-size-fits-all approach to treating advanced prostate cancer to a much more effective approach where drugs target the genetic drivers of an individuals cancer. Thanks to you Olaparib is ready to blaze a trail for future precision medicines of this kind.
This is by no means the end of the story. Theres still plenty of work to do to ensure that all the men who can benefit from drugs like Olaparib can get access. We will continue to champion the use of Olaparib, through working with the relevant pharmaceutical company, healthcare regulators, researchers and men to make sure this happens.
Help develop our precision treatment programme by donating today.
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New Drugs Approved For Advanced Brca
- By Charlie Schmidt, Editor, Harvard Medical School Annual Report on Prostate Diseases
Defective BRCA genes are well known for their ability to cause breast and ovarian cancers in women. But these same gene defects are also strong risk factors for aggressive prostate cancer in men. About 10% of men with metastatic prostate cancer meaning cancer that is spreading away from the prostate test positive for genetic mutations in BRCA genes. Fortunately, these cancers can be treated with new types of personalized therapies.
In May, the FDA approved two new drugs specifically for men with BRCA-positive metastatic prostate cancer that has stopped responding to other treatments. One of the drugs, called rucaparib, was approved on May 15. The other one, olaparib, was approved on May 19.
Both drugs work by shutting down the cancer cells ability to fix its DNA. Like all cells in the body, cancer cells are bombarded every day by free radicals, low-level radiation, and other stressors that cause DNA damage. BRCA genes ordinarily fix that damage so that cells can function normally and survive. But if the genes are defective, then the damage piles up. BRCA-positive tumors get around that problem by deploying an alternate DNA repair gene called PARP. Rucaparib and olaparib both inhibit PARP, leaving cancer cells without any way to fix their increasingly mangled DNA eventually the cells die.
Q: Why Is There Such An Urgent Need For Treatments For This Type Of Prostate Cancer
We know that patients with prostate cancer who have certain mutations face a worse prognosis, but unfortunately there are currently no PARP inhibitor combinations available to them until very late in the disease. We are evaluating the benefits and the risks of giving these combination treatments earlier in metastatic disease progression, before patients receive treatments like chemotherapy.
Current treatment guidelines in the U.S.recommend that all patients with metastatic prostate cancer, and some with localized prostate cancer who have identified risk factors such as a family history of the disease, receive genetic testing. But many patients with prostate cancer arent routinely screened for these relevantmutations, which may also impact treatment.
For example, a survey published earlier this year in the Journal of the Canadian Urological Association found that only a little over a third of oncologists recommended that their patients with newly diagnosed metastatic prostate cancer go for genetic testing. And a recent analysis of more than 5,000 U.S. patients with metastatic prostate cancer found that only 13% had documented genetic testing.
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Triton2 Leads To Accelerated Approval For Rucaparib
FDAs approval for rucaparib, announced on May 15, is slightly different than what was granted to olaparib.
To begin with, it was an accelerated approval. That means the approval was granted based on results from a clinical trial that strongly suggests rucaparib could be beneficial for patientssuch as an improvement in progression-free survivalalthough that level of proof is not yet available.
In addition, the approved use is only for men with mutations in BRCA1 or BRCA2 and only for cancer that has progressed despite earlier treatment with both a hormone-blocking treatment as well as chemotherapy.
The approval was based on the results of a 115-patient clinical trial, called TRITON2. Similar to the PROFOUND trial, TRITON2 enrolled men with alterations in a host of DNA repair genes, the largest group of which was those with BRCA2 mutations. All the men in the trial were treated with rucaparib.
According to data presented at the ESMO meeting late last yearand similar to what was seen in PROFOUNDmen with BRCA2 alterations were most likely to respond to the PARP inhibitor. Of the 62 men with BRCA2 alterations, nearly 45% had a tumor response. And, in more than half of these men, the response lasted for at least 6 months.
Overall, Dr. Karzai said, it does appear that BRCA2 alterations really do drive the benefit of PARP inhibitors among men with metastatic prostate cancer. I think were really seeing that in these trials.
The Initial Causes Biomarkers Prostate Cancer Palb2 Ntrk Brca1
One of the first symptoms of prostate issues is pain or tenderness in the groin or lower back. This can be the result of a noncancerous condition called enlarged prostatic tissue, or it could be an infection of the bladder. In either case, its important to see a doctor as soon as possible. If youre suffering from prostate pain, you may want to consider reducing your caffeine intake.
Another symptom of a potentially enlarged prostate is difficulty starting a stream of urine, leaking, or dribbling. These symptoms are not serious, but theyre still alarming. Most men put up with an enlarged prostate for years before seeking medical attention, but they typically seek treatment as soon as they notice symptoms. Even if you dont have symptoms, its worth getting checked to determine if you have any prostate issues.
If you experience nightly bathroom runs, you may be experiencing an enlarged prostate. You may be having difficulty starting a stream of urine, or you may even be dribbling or leaking during the day. These problems arent life-threatening, but can become a nuisance. You should not ignore these signs and seek treatment as soon as you notice them. If you feel any of these symptoms, you should consult a doctor.
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Breakthrough: World’s First Precision Prostate Cancer Treatment
This weeks results offer a brand-new precision treatment option for a group of men with particularly aggressive forms of advanced prostate cancer.
Precision medicine is an exciting and effective approach to cancer care that uses information about the genetics of a mans tumour to work out the best treatment for him.
New research presented at the ESMO conference this week is the final piece of the puzzle to show the drug olaparib could be the first-ever precision medicine treatment for prostate cancer.
The drug is part of a class of drugs called PARP inhibitors, which target defects in cancer cells’ ability to repair damage to their DNA. Recent results from a new study have shown that Olaparib could delay the progression of advanced prostate cancer for over four months. Crucially, the men who responded all had mutations in one of 15 genes in their prostate cancer, including BRCA.
It marks a landmark achievement in treating advanced prostate cancer. But this breakthrough didnt happen overnight. It’s the result of two decades worth of research, funded by you, to unpick the genetics behind prostate cancer to create new precision treatments.
Heres a deep dive into how we got to this incredible milestone.
About The Medical Reviewer
Dr. Mark Pomerantz is a medical oncologist at the Dana-Farber Cancer Institute. Dr. Pomerantz received his undergraduate degree from Yale University and his medical degree from Stanford University. He trained in Internal Medicine at Brigham and Women’s Hospital in Boston, Massachusetts. He then pursued a fellowship in Medical Oncology at the Dana-Farber Cancer Institute in Boston. Dr. Pomerantz received his post-doctoral training in cancer genetics with Dr. Matthew Freedman at the Dana-Farber Cancer Institute and the Broad Institute of Harvard and MIT. He is on faculty at the Dana-Farber Cancer Institute in the Lank Center for Genitourinary Oncology.
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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.
Brca2 Mutations Linked To Worse Outcomes Treatment Responses In Aggressive Prostate Cancer
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Germline mutations in the BRCA2 gene have an adverse effect on metastatic castration-resistant prostate cancer outcomes that could be modified by the type of initial treatment used, according to results of a prospective, multicenter study published in Journal of Clinical Oncology.
Our study shows that treatment and follow-up protocols used in patients with advanced prostate cancer may be inadequate for men with BRCA2 mutations,David Olmos, MD, PhD, head of the prostate cancer clinical research unit at Spanish National Cancer Research Center, said in a press release. We are currently studying the characteristics that make these tumors more aggressive and trying to establish new strategies to improve patient prognosis.
The results are the first from the PROREPAIR-B study involving 38 Spanish hospitals and 419 men diagnosed with metastatic castration-resistant prostate cancer. Researchers screened the men for germline DNA damage repair mutations in 107 genes and followed the men for up to 5 years to assess the impact of mutations on disease progression and response to treatments.
The cohort included 68 mutation carriers, including 14 men with BRCA2 mutations, eight with ATM mutations and four with BRCA1 mutations. None of the patients had a PALB2 mutation.
Elena Castro
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