Caring for the Whole Family

If you have high-risk or advanced prostate cancer, you may have been born with a faulty gene. Genetic testing is recommended. A PCF-funded research project aims to make it easier for your family to get tested, too.

Sokolova did germline genetic testing (looking at Eddie’s blood for inherited, cancer-linked mutations) and discovered a faulty BRCA2 gene – a mutation most famous for raising the risk of breast and ovarian cancers (see Key Terms box below).  Eddie said, “My sister has that.”

One sister had been diagnosed with breast cancer years before. “All his sisters got germline genetic testing,” says Sokolova (this is called “cascade genetic testing,” of family members after someone is diagnosed with a mutated gene). “But he didn’t – because he was a man.”  

Eddie and his family didn’t think this gene was something he needed to worry about, and for many years, doctors didn’t think so, either.  Even BRCA2’s name (an abbreviation for “BReast CAncer gene”) and the syndrome it is associated with (Hereditary Breast and Ovarian Cancer Syndrome) now seem misleading – because mutations in BRCA2 and BRCA1, a related gene, are known to raise the risk of prostate cancer, too.  These and others are “DNA damage-repair genes” – genes that are supposed to act as quality control agents, preventing genetic mistakes from being passed on when a cell divides. 

If Eddie had known he was at higher risk, his prostate cancer might have been detected much earlier.  Sokolova thinks about Eddie a lot, and she has dedicated her career to helping high-risk patients and their families.  “About 12 percent of men diagnosed with metastatic prostate cancer were born with a bad gene,” she says.  “If you inherited a mutation in BRCA1 or BRCA2, you are not only at higher risk of getting certain cancers, including prostate cancer:  you are also likely to develop a more aggressive form of prostate cancer.  Patients with these mutations tend to be diagnosed at a younger age, at a more advanced stage of prostate cancer, and are more likely to have a shorter survival.”

Early knowledge is a game-changer.  The best help Sokolova can provide for patients like Eddie is to arm him and his family with information that could save their lives:  to test men diagnosed with high-risk or metastatic prostate cancer and, if BRCA2 or a similar faulty gene is found, to do “cascade” testing – to test his immediate family.

An inherited cancer gene has a ripple effect.  “If your mother had an inherited BRCA2 mutation, there is a one-in-two (50 percent) chance that you or your siblings inherited the same mutation, and a 25 percent chance that your children did.  Just knowing you have such a gene mutation has significant implications for treatment decisions.”  For example, if you know the genetic deck is stacked and not in your favor, you should consider more aggressive, curative treatment for prostate cancer.  Also, germline testing can identify patients who are candidates for PARP inhibitors, drugs such as olaparib that have proven effective in cancers when there is a mutated DNA repair gene.  Another advantage of early knowledge, Sokolova continues:  “At-risk family members can implement cancer prevention and early detection strategies, and possibly consider risk-reduction surgery.”  

Who Should Consider Germline Testing?

Does everyone with prostate cancer need genetic testing?  No.  Many men are diagnosed with low-risk or intermediate-risk localized cancer, cancer that may not need to be treated immediately or maybe even ever.  Sokolova says you should consider germline testing if:

You were diagnosed with high-risk localized prostate cancer:

• Your PSA was over 20 at diagnosis;
• Your Gleason score was 8 or higher;

You were diagnosed with stage T3 cancer (which extends past the prostate or has spread locally); or if you were diagnosed with metastatic prostate cancer, which has spread to sites away from the prostate;

Your pathology report shows evidence of intraductal carcinoma or cribriform glands, findings associated with more aggressive cancer.

Family history is a red flag, too:  You should also consider germline testing if your family history includes:

One or more close relatives diagnosed with breast, pancreatic, ovarian, colorectal, or prostate cancer at age 50 or younger; or a relative diagnosed with metastatic, high-risk, or very high-risk prostate cancer;
Two or more close relatives diagnosed with breast cancer or prostate cancer at any age;
Three or more close relatives with Lynch syndrome, a hereditary disorder that raises risk of developing many forms of cancer, particularly colorectal and endometrial cancer;
A family history of Li-Fraumeni syndrome (also known as SLBA, for inherited predisposition to Sarcoma, Breast, Leukemia, and Adrenal cancers);
You are of Ashkenazi Jewish ancestry;
You have a known family history of a germline mutation;
You have a personal history of (male) breast cancer. 

These detailed criteria are updated frequently based on new research findings, so be sure to speak with your doctor about your prostate cancer diagnosis and your family cancer history.  Use this family tree tool to guide conversations with your family to collect this information.

How is Germline Testing Done?

It’s not hard at all, says Sokolova:  “You can have germline testing through a blood test, or you can spit in a tube.  This test can be ordered by your doctor, or you can order it yourself,” through companies such as Color Health or Invitae (through Labcorp).  There are also research websites, where patients can register themselves. “The test gets sent to your house, you spit in the tube, send it back and get the results online,” says Sokolova.  One of these is through the PROMISE study.  “If you have prostate cancer, you can register with www.prostatecancerpromise.org and get free genetic testing.”

Here are some points to consider: 

Not all online genetic testing is the same.  Some tests marketed directly to consumers are “considered recreational, and lack the ability to detect clinically important mutations,” says Sokolova.   Clinical genetic testing looks for a larger panel of hereditary genes, so talk to your doctor, do your research, and make sure you know what kind of test you are getting. Also:

“If you got genetic testing 20 years ago, it’s worth talking to your doctor about repeating the testing, because it has gotten better over the years,” Sokolova adds.      

Protect yourself.  It is against the law for your health insurance company or workplace to discriminate against you because of any risks turned up in genetic testing.  But life insurance and disability insurance are not protected.  Therefore, before your family members undergo cascade testing, especially younger relatives who might not have thought much about life and disability insurance, they “should consider getting those policies in place beforehand,” Sokolova suggests.  Learn more about the Genetic Information Nondiscrimination Act (GINA) here.

Could Doctors Do a Better Job of Testing Families?

With Eddie and his family in mind, Sokolova has launched a PCF-funded project looking to make it easier for families to get cascade genetic testing.  “Traditionally,” she explains, “patients find out they have a mutation, then the doctor says, ‘Here’s a letter for your family.  Please make sure you talk to your relatives, because they’re at higher risk of getting certain cancers.’  This could be really overwhelming for patients.” 

Sokolova’s project centers around provider-initiated, rather than patient-initiated, cascade testing.  “If you have prostate cancer and meet the eligibility criteria – a mutation in a DNA repair gene such as BRCA2 – then your first-degree family members (sons, daughters, brothers, sisters, and parents) are eligible for free testing as part of the study.  We’ll be happy to reach out to your family members anywhere in the U.S. and discuss the importance of getting tested.  If they agree, we send a kit to their house, they spit in the tube, get the results over the phone or through a portal, and we try to find them a local genetic counselor.”  To find out more, please visit the study website, call (503) 494-3456 or email  [email protected]           

“Our goal is ultimately to improve cancer prevention in families with inherited cancer.”  In other words, not only to care for the patient, but for the whole family.            

*Name has been changed to protect this patient’s privacy.

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The Turning Point in Prostate Cancer Genetics

There was an earthquake in the prostate cancer community on July 6, 2016.  That was the day a landmark study, funded largely by PCF, was published in the New England Journal of Medicine.  An international team of investigators found germline mutations in 16 genes, including BRCA, ATM, CHEK2, BRCA1, RAD51D, and PALB2.  These mutations were significantly more common in men with metastatic prostate cancer than in men with localized disease.

Because of this work, genetic tests now routinely look for these faulty genes in men with metastatic prostate cancer.  Learn more about how PCF-funded research is helping uncover the importance of prostate cancer genetics here. 

If you have a mutation in one of these genes, your sons and daughters, and their children need to know about it, because they are more likely to develop cancer, too.  This could be prostate cancer, breast cancer, ovarian cancer, pancreatic cancer, or other, less common cancers. 

Note:  This means that relatives with this mutation need to be screened for cancer more vigilantly, and starting at a younger age.  It doesn’t mean that cancer is inevitable.  It just means that the risk is higher for those who have this same mutation, and that if cancer is found, doctors will be more aggressive about treating it right away.   People with a cancer-related gene mutation may also consider certain lifestyle changes to help reduce their risk of developing cancer.