Expert Talks the Who, What and When of Breast Cancer Genetic Testing


By understanding family history, an individual can better reveal their genetic breast cancer risk and whether or not they are a candidate for genetic testing.

It’s a question asked at many doctor visits: “What is your family health history?” When applied to breast cancer risk and prevention, knowing the answer can save lives.

At the recent CURE® Educated Patient® Breast Cancer Summit, Dr. Leif Ellisen delved into the topics of inherited breast cancer risk, genetic testing and management, so that patients can be armed with the correct information prior to their doctor visit.

“It's important for all of us to remember that most breast cancer in society is not caused by genetic causes, it's caused by individual risk factors. And frankly, bad luck,” said Ellisen, who is the program director of breast medical oncology and clinical director of breast and ovarian cancer genetics at Massachusetts General Hospital. “…That's not to say we can't do things to decrease our risk, but that ultimately, most breast cancers are not caused by hereditary factors.”

Currently, breast cancers that are caused by individual genes that increase risk of breast and other cancers can be focused on in terms of clinical management.

“In the future, we'll have probably better markers for breast cancers that are caused by the sum of many different genes we inherit,” Ellisen said.

The genes that put someone at high risk for breast cancer are very uncommon in the general population. Low- or moderate-risk genes are more common, but the risk of breast cancer from them is lower and thus they give rise to fewer breast cancers.

Who Needs Genetic Testing?

While breast cancer caused by hereditary factors is not super common, patients may still wonder if they’re one of the unlucky few. Ellisen highlighted several red flags for hereditary breast and ovarian cancer that signify whether someone should undergo genetic testing.

Anyone with ovarian cancer (at any age) should be tested – if there’s a family history (on either side) and the person who had ovarian cancer can’t be tested, other family members should be. Those diagnosed with triple-negative breast cancer of any stage should undergo testing, as well as anyone who received a breast cancer diagnosis before age 50. Male breast cancer is uncommon, and any family history of it signifies there could be hereditary breast cancer in the family; therefore, relatives should be tested. People who have had multiple primary cancers should be tested, as that is also a possible sign of inherited risk.

Individuals with Ashkenazi Jewish ancestry should also be tested, as BRCA1 and BRCA2 mutations occur in about one in 40 of Ashkenazi Jewish people.

Lastly, if an individual is known to have a mutation, their close family members should be tested as well.

What Genetic Tests Look For

Genetic tests vary, as there are many different types in terms of what genes they’re testing for and which company is providing the test.

“It turns out that most folks now are recommended to have multi-gene panel testing somewhere between seven to nine and 30 or more genes testing for hereditary cancer,” Ellisen explained.

What an individual is tested for may depend on their family history and potential risk. For example, for someone with a family history of ovarian cancer, there is a whole series of genes to test for.

“For folks who have a mixed family cancer history – maybe a mix of breast cancer, ovarian cancer, kidney cancer, colon cancer –more than 30 genes might be indicated, in some cases,” Ellisen said.

The important takeaway is that patients should speak with their health care provider about what kind of genes they’ll be tested for.

Interpreting test report

Understanding the findings of a genetic test can get confusing, even for health care providers, Ellisen clarified.

“We categorize the findings of genetic testing into things that are meaningful, and those are called deleterious or suspected deleterious. Another term that's used is pathogenic – so pathogenic or likely pathogenic.”

Whether or not a mutation is deleterious will impact how the patient’s health is managed.

There is also something called a variant of uncertain significance (VUS), which are very common but should typically not be used to inform decisions on screening, surgery or therapy.

“And so you might ask the question, ‘Well, if we don't know, meaning there's unknown significance, should I really be worried about this gene, whether it means something?’” Ellisen said. “And these differences of these VUS (findings), most of them are literally like the difference between your fingerprint and mine. Yes, it's a difference. But no, it doesn't mean anything in terms of your health. And that's why often there's a controversy about whether we even need to report VUS, but definitely they should not be used importantly to guide management.”

Risk Assessment and Screening Recommendations

If a patient is found to carry a certain mutation that puts them at risk for breast cancer, the next steps may vary depending on what type of mutation it is.

For the two most common breast and ovarian cancer genes, BRCA1 and BRCA2, it’s important to factor in a patient’s age. Breast cancer occurs earlier (with these mutations) than ovarian cancer.

“Typically, there’s a 10-year window when breast cancers occur, as early as the 20s and 30s, whereas most ovarian cancers occur in the late 40s and beyond with BRCA1 and 2,” Ellisen said. “And that affects how we screen, and that affects how we manage these.”

For BRCA1 and BRCA 2 carriers, semiannual clinical breast screenings begin at age 25, while self-exams should be done monthly starting at age 18. Women with BRCA2 are recommended to have both an MRI and mammogram done each year after 30 (with MRI screenings beginning at age 25). The health care providers may also discuss the option of preventive mastectomy with patients and removing the ovaries and tubes – not always the uterus.

“This can prevent the cancers. And the main choice is about doing it at the right age. It needs to be considered at a younger age for BRCA,” Ellisen added.

Beyond BRCA1 and BRCA2, there are several other common genes found through testing that are important to know about, because the recommendations differ. These include ATM, CHEK2, PALB2, PTEN, TP53 and NBN. Because the risk for breast cancer varies among them depending on the gene, some patients may be directed to undergo screenings while others may be encouraged to have a preventive mastectomy.

For the genes considered high-risk (TP53, PTEN, CDH1), providers may discuss screening or preventive mastectomy. For the more moderate-risk genes (PALB2, ATM, CHEK2, STK11), the recommendation is to undergo screening (at a later age than for high-risk genes) and discuss mastectomy if the family history shows red flags.

How Do Genes Factor Into Treatment?

PARP inhibitors were designed with the goal of complementing and providing effective therapy for tumors caused by BRCA1 and BRCA2, Ellisen explained. They’ve demonstrated successful results in breast, ovarian, pancreas and prostate cancers.

“What's very exciting is it looks like PARP inhibitors are actually preventing the ultimate development of metastasis,” he said.

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