Testing for breast cancer gene mutations is for you – and future generations

Depending on your gene pool, the best cancer preventive might be a simple blood or saliva test.

In the mid-1990s, the discovery of the BRCA1 and BRCA2 gene mutations revolutionized breast cancer prevention and treatment. Doctors were able to identify women – including actress Angelina Jolie – who were at statistically greater risk.

These days, genetic testing goes much further, said Nancy O’Connor, nurse practitioner in the High-Risk Hereditary Cancer Program at Cuda Women’s Health Center at Cape Cod Healthcare. It’s a crucial diagnostic tool, allowing clinicians to focus on prevention and early detection for breast, ovarian, prostate and pancreatic cancers, among others.

“Having a gene mutation – the new term is pathological variant – doesn’t mean the person will develop cancer, but it does mean they’re at elevated risk,” O’Connor said. “What we’re trying to identify is who’s at higher risk, so we can [connect] them with the appropriate specialist, do increased surveillance and have some measures for protection.”

Cancer cannot be inherited, but up to 10 percent of cancers may be caused by inherited genetic variants – genes that go awry, according to the National Cancer Institute. Researchers have now discovered hundreds of gene and DNA variants that encourage cancers to form or spread, the institute says.

The BRCA1 variant, in 1994, and BRCA2, in 1995, were the first to be discovered, according to the National Human Genome Research Institute. Researchers estimated that by the age of 70, slightly more than half of all women with one of the BRCA alterations would develop breast cancer and about one out of every six would develop ovarian cancer. Children and siblings of people with the BRCA gene variant have a 50 percent chance of carrying it, O’Connor said.

“That’s what we call that cascade effect,” she said. “When one person gets tested, it can affect all those other family members. So, we always try to test the person who's been affected by cancer, because typically if they're negative, then we know that it's unlikely that there is that gene change in the family.”

At first, genetic testing was expensive, and doctors targeted women in their 40s or younger, O’Connor said. But in 2013, Jolie raised awareness when she went public about having a double prophylactic mastectomy because she carried a BRCA1 variant. Meanwhile, researchers were tracking gene variants that caused prostate, pancreatic and ovarian cancers. In 2014, another advancement allowed doctors to request multi-gene testing panels, O’Connor said. So far, 11 genes have been associated just with breast cancer, she said, and now routine tests cover 48 genes, including those associated with renal, kidney, and thyroid cancers.

The National Comprehensive Cancer Network, a nonprofit alliance of 32 top cancer centers in the U.S., sets the guidelines for who meets criteria for genetic testing, and “it expands all the time,” O’Connor said. Currently it includes all women with breast cancer and men with breast cancer at any age, metastatic prostate cancer and pancreatic cancer, she said.

BRCA variants remain the most commonly found among breast cancer patients, she said.

“I would say 65 to 70 percent of the time, if a woman has breast cancer and it’s positive for a gene mutation, it’s the BRCA1 or 2.”

How It Works

The tests use a sample of blood or saliva, although in rare circumstances testing may require a punch skin biopsy that captures a deeper layer of tissue, she said. Insurance usually covers the cost if the patient meets cancer network criteria, although some labs are offering a cash option for people who don’t meet the guidelines but want to be proactive, she said. And, 23andMe, a private company, includes the BRCA profile in its mail-order $200 DNA tests, according to the company’s website. However, their tests are limited, only detecting three out of the possible 1,000 BRCA variations, according to the company’s website.

Results go into a patient’s medical record and are shared with providers, but the genetic testing company destroys the sample and does not share the data, O’Connor said.

“Privacy is a very important part of it,” she said.

There are several reasons to get tested, O’Connor said. For starters, genetic results guide treatment. She used the example of an imaginary Cuda patient found to have the BRCA1 mutation. Instead of lumpectomy, the patient might opt for a full mastectomy because there is higher risk of recurrence with a gene patient, O’Connor said. Or, she might consider a risk-reduction mastectomy on the unaffected breast or having her ovaries or fallopian tubes removed since BRCA1 increases the risk of ovarian cancer. Some medications work more effectively when patients have a BRCA1 or BRCA 2 mutation, she said. And, once they get their results, patients may want to encourage other family members to get tested.

But people should understand that a positive genetic test doesn’t always mean cancer, O’Connor said. And it’s important for men and women to be tested if there’s a family history of a type of cancer - ovarian, for example – that could be genetic.

“They might never develop cancer, but they can pass on the (pathogenetic variant) gene mutation,” O’Connor said. “That’s a big message I try to get out there. Especially when I give results, women will say, ‘Oh, that’s good [knowledge] for my daughters.’ And I’m saying, ‘it’s good for your daughters and sons, grandsons and granddaughters.’”