Testing for BRCA: What Is the Best Way to Screen for Cancer Genes?

MSK clinical geneticist Kenneth Offit and genetic counselor Yelena Kemel pictured in a laboratory

Clinical geneticist Kenneth Offit (left), shown here with genetic counselor Yelena Kemel, is leading a study on BRCA testing.

In March 2018, the US Food and Drug Administration approved an at-home, mail-in kit that tests for some of the inherited mutations in the genes BRCA1 and BRCA2. These mutations are linked to an increased risk of breast cancer, ovarian cancer, and prostate cancer, and possibly others.

Storefront centers that conduct cholesterol checks, do thyroid panels, and screen for sexually transmitted diseases have made people more comfortable initiating their own medical tests. But many experts say that some types of testing — including for cancer genes — should continue to be done under a healthcare provider’s guidance.

“The developers of at-home genetic tests have said they should be as easy and available as a pregnancy test, which any woman can take at home alone in her bathroom,” says Kenneth Offit, Chief of MSK’s Clinical Genetics Service. “But that’s exactly what we’re worried about. For men and women, finding out that you’ve inherited a cancer gene can raise a lot of issues. We want to make sure that people who receive these results are getting the support that they need.”

To answer some of the questions about the best way for people to get this kind of health information, a team of clinical genetics experts has launched the BRCA Founder Outreach (BFOR) study. The study is being led by Memorial Sloan Kettering and three other cancer centers.

This is not recreational genomics, which is what most home-testing kits have traditionally been. The stakes for these kinds of cancer genetic tests are much higher than just looking at your ancestry.
Kenneth Offit Chief of the Clinical Genetics Service

A Contrast to Recreational Genomics

“Thanks to new avenues of communication and education, we can enhance genetic counseling and widely share the knowledge of top experts when screening for cancer genes,” explains Mark Robson, Chief of the Breast Medicine Service and a co-principal investigator of the study. “BFOR is designed to help us do that.”

The purpose of the BFOR study is to evaluate how to best combine the convenience of direct-to-consumer genetic tests with guidance from a medical care provider. It will allow 4,000 women and men with Jewish ancestry to enroll in screening for the three most common BRCA mutations linked to increased cancer risk. These mutations are quite rare in the general population, but one in 40 people of Ashkenazi (Eastern European) Jewish descent carries at least one of them.

“This is not recreational genomics, which is what most home-testing kits have traditionally been,” says Dr. Offit, who is one of the principal investigators and head of the executive committee running the BFOR study. “The stakes for these kinds of cancer genetic tests are much higher than just looking at your ancestry.”

People who are age 25 and older and have one or more Ashkenazi Jewish grandparent can go to the BFOR website and fill out a questionnaire to determine whether they are eligible. Once they complete the online educational and consent process, they can go to a local Quest Diagnostics center to get a blood test. Quest is providing testing at no charge to the study participants.

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Explaining Potentially Life-Changing Genetic Test Results

Under the BFOR model, participants receive the results from someone who can explain what the findings mean, rather than getting them in the mail. They can choose whether to get their results from a clinical genetics expert or their own doctor. Some of the issues raised by learning of an increased cancer risk include whether to consider risk-reducing surgery and how to inform other family members who may also carry the mutation.

Currently, the study is limited to people living in metropolitan areas that have participating centers, so they have access to genetics experts. In addition to MSK in New York City, the other sites involved are Dana-Farber Cancer Institute and Beth Israel Deaconess Medical Center in Boston, the University of Pennsylvania in Philadelphia, and Cedars-Sinai Medical Center in Los Angeles.

Another important note is that with both the BFOR study and the commercial genetic-testing service, only the three most common BRCA mutations are included. These three mutations account for about 95% of BRCA1 and BRCA2 mutations in Ashkenazi Jews. BRCA mutations overall explain only about a quarter of inherited breast cancers.

To learn more about participating in the BFOR study, visit the website or call 833-600-BFOR (2367).

“Just because you test negative for these three BRCA mutations doesn’t mean you’re in the clear, especially if you have a strong family history. You may need to decide if you want to undergo additional testing,” explains Kelly Morgan, a genetic counselor dedicated to this study. “This is just another illustration of why working with a trained healthcare provider is so important.”

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Founders in the Field of Cancer Mutations

The three mutations included in the study — two in BRCA1 and one in BRCA2 — are called founder mutations. A founder mutation is a genetic change that appears with high frequency in a small group of people who were geographically or socially isolated for a long time and had ancestors who carried that specific gene mutation. Because Ashkenazi Jewish populations were culturally separated for hundreds of years, these BRCA mutations, which initially occurred by chance, became more common in that group.

In 1996, Dr. Offit and his team discovered the most common BRCA2 mutation linked to breast and ovarian cancers. The mutation has since been linked to other cancers, including prostate cancer and pancreatic cancer. Around the same time, other research groups identified the two BRCA1 founder mutations.

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Teaming Up with the Community

Dr. Offit emphasizes that as a National Cancer Institute–funded cancer center, MSK counts treating the community in which it’s located as one of its primary roles. About two million people of Jewish descent live in the New York City metropolitan area, most of them Ashkenazi, and 20% of people treated at MSK have Jewish ancestry, making this focus especially fitting.

However, he notes, the information gained from focusing solely on this group in the BFOR study can later be applied to the wider population, just as other BRCA-related findings have been more broadly applied in the past.

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Funding information: The BFOR study is supported by the Sharon Levine Corzine Foundation. Dr. Offit’s research is also funded by the Robert and Kate Niehaus Foundation and MSK’s Robert and Kate Niehaus Center for Inherited Cancer Genomics.


Commenting is disabled for this blog post.

is this genetic test only for Jews?

Dear Dawn, the BFOR study is currently open only to people of Ashkenazi Jewish descent, because those people are the ones who are most likely to have the three particular mutations that are being looked at in this study. However, people of any background can have mutations in the BRCA genes. If you are interested in learning more, we recommend that you ask your doctor for a referral to a genetic counselor. Thank you for your comment, and best wishes to you.

A former patient of Dr. Offit’s Servicein 1996, I was found to have the BRCA 1 Gene. Counseling empowered me to choose prophylactic double mastectomies at MSKCC. I have never regretted my decision.

Now my two sons in their forties are considering genetic counseling. What do you advise they pursue?

Thank you!

Dear Maria, we’re so happy to hear that you were pleased with the care you received from Dr. Offit and from MSK. If your sons would like to make an appointment to speak with someone from MSK’s Clinical Genetics Service, they can call 646-888-4050 or go to https://www.mskcc.org/cancer-care/risk-assessment-screening/hereditary-… for more information. If they don’t live in the New York City area, we recommend that they seek out a genetics clinic that has experience in working with people who have a family history of cancer. They may want to consult a list of National Cancer Institute-designated cancer centers to find one that is close to where they live. You can find that here: https://www.cancer.gov/research/nci-role/cancer-centers

Thank you for your comment and best wishes to you and your family.

I would like make an appointment with someone in MSK ‘s Genetics Service
I have history family cancer.
Thank you

I have the ATM gene and in 2017 was dianosed with right breast cancer. I was negative for braca1 and braca2. Should my 25 yo be tested for this atm gene?

Dear Claudia, people who inherit this gene from their parents do have an increased risk of cancer, and there is a chance that your child could have inherited it from you. If he or she would like to come to MSK for testing, they can call 646-888-4050 to schedule an appointment. You can go to https://www.mskcc.org/cancer-care/risk-assessment-screening/hereditary-… for more information. If they are not in the New York area, they should seek out a specialist in cancer genes who is close to where they live. Thank you for your comment and best wishes to you and your family.

Prior patient of MSK I believe I am an exceptional survivor. Let me summarize, then address my concerns regarding my sons. I’m 70
Late 80’s malignant melanoma stage 4
Georgetown university hospital groin lymph nodes removed then submitted to MSK I believe Dr Livingston’s? Vaccine bcg? 30 years no recurrence!
2011 pure coincidence...in hernia surgery found primary peritoneal carcinoma stage 4 again... Many usual protocols, tested genes, found BRCA2.. NO IDEA from whom... Dad American died 85 yrs old, mom Italian BUT east European descent died 63 heart disease. Her grandmother I believe had a Jewish last name Zoppis, but not sure! I'm presently down to Ca125 280 on Zejula, glad to be here but worried about 2 sons (40’s) and grandchildren. Please advise how can I find if I’m part ashteneki Jewish and can BRCA 2 skip 4 generations?

Dear Ingrid, we’re sorry to hear about your cancer history but glad to hear you are doing well now. BRCA gene mutations do not “skip” generations, but not everyone with a BRCA mutation will ultimately develop cancer. If you carry a BRCA2 mutation, there is a 50 percent chance for each of your sons that they have it. If one or both of them have it (and only if they have it) there is a 50 percent chance that their children have it. It’s important to note also that not all BRCA mutations are particular to people of Ashkenazi Jewish descent. People of other backgrounds can have mutations in these genes as well. If your sons are interested in getting tested, they can contact MSK’s Clinical Genetics Service at 646-888-4050. If they are not in the NYC area or not able to come to MSK, we recommend that they find a genetic counselor who specializes in working with people who have a family history of cancer. Thank you for your comment and best wishes to you and your family.