An NCI-designated Comprehensive Cancer Center
By Abe Rosenberg | October 25, 2017
When Ming* was first diagnosed with breast cancer on her right side, she knew she'd need surgery. But at her doctor's urging she also took an additional step, scheduling a session with a City of Hope genetic counselor.
“I just had a feeling,” she recalled. “My aunt had breast cancer. My uncle had prostate cancer. I wanted to know for sure, for my sake and my family's. I have two teenage daughters.” She requested the broadest available screening panel, to test for as many genetic mutations as possible.
What she learned didn't surprise her, but it did help her decide what to do next.
Ming was found to carry a CHEK2 gene mutation in her body, which carries a 20 to 30 percent lifetime risk of breast cancer (as well an elevated risk of colon cancer). CHEK2 mutations are less dangerous than the 80 percent risk of the better-known BRCA1 or BRCA2 gene defects, but Ming still didn't feel comfortable with the odds. 
Although no cancer had been detected on her left side, Ming nonetheless chose to have a bilateral mastectomy.
“We see that a lot,” said City of Hope genetic counselor Lauren Gima. “A fair number of patients come to us after they've been diagnosed, not only to learn the “why” of their cancer, but also to help decide what to do about it.”
When it comes to cancer, the “why” is not usually heredity but the risk factors of our individual lives. If you smoke, if you're obese, if you're exposed to toxic materials at work, your cancer risk goes up. Overall, according to the National Cancer Institute, inherited genetic mutations account for no more than 5 to 10 percent of all cancers. 
The numbers may be low, but as we learn more about the different mutations linked to breast cancer, some experts are taking a “better safe than sorry” approach, recommending more widespread genetic counseling and testing.
Thomas Slavin Thomas Slavin, M.D.
“I believe many more people need testing than they think,” said City of Hope clinical geneticist Thomas Slavin, M.D. And not just for BRCA gene defects, which account for most hereditary breast cancer cases, but also for mutations that carry a more “moderate” risk, like the gene CHEK2, and others with names like PALB2 and ATM. 
There are also rare mutations in the gene TP53 gene which can raise the cancer risk even higher than BRCA mutations do, in some cases approaching 100 percent.
When free of defects, all these genes help regulate cell growth, repair damaged DNA and prevent tumors from forming. “They make sure the bodies cells copy themselves properly,” said Slavin. A change, or mutation in that process can make cancer more likely.
Because you inherit one set of genes from each parent, you run a 50 percent chance of carrying a genetic mutation if your mom or dad had it. 
“We always start with a lot of questions about your health and your family history,” said Gima. “That helps us determine what kind of testing is appropriate.”
But who should get tested and who need not?
The guidelines can be a bit “convoluted,” said Slavin, and many physicians don't know them well, though that situation is slowly improving. Still, there are red flags.
While most nonhereditary cancers are diagnosed in older people, inherited cancer generally shows up earlier, because the genes' tumor suppression mechanism has been damaged since birth. So if a close relative had breast cancer or other cancers at a young age, it's cause for concern.
Slavin gets more specific:
If someone in your family had triple-negative breast cancer before age 60, any breast cancer under age 46, bilateral breast cancer before age 50 or ovarian cancer at any age, you should get tested.” 
Other possible warning signs:
  • Cancer in the family, plus Eastern European (“Ashkenazi”) Jewish ancestry (BRCA mutations occur more frequently in this population).
  • More than one relative diagnosed with breast, colon, prostate or pancreatic cancer on the same side of the family.

Even if you don't fit exactly into any of those categories, Slavin said it may still be worthwhile to talk with a counselor if you are concerned.
“My general take is, if you're concerned, come see us,” he said. “Even if we determine that testing isn't necessary, you'll gain knowledge that will help you manage your personal cancer screening.” For example, your family history may make it advisable to get “enhanced” surveillance – like earlier mammograms or breast MRIs-  just to be safe.
If the counselor does recommend testing and you go forward with it, the results will arrive in a few weeks, and they'll fall into one of three categories:
  • Positive: A defect has rendered a key gene – like BRCA – nonfunctional. This indicates an elevated cancer risk.
  • Negative: No defects were found. 
  • VUS: This refers to “variants of unknown significance.” Mutations are present, but it's not known if they've altered the proper functioning of the gene. This may sound maddeningly uncertain, but genetic counselor Gima is reassuring.

“Up to 90 percent of our VUS findings will ultimately be downgraded to 'benign',” she said.

Here's where knowledge and experience play such a vital role. After the test results come in, it's important to sit with the counselor again, to fully understand what the numbers mean. Genetic counselors tread carefully, taking into account the nuances of risk levels, balanced with the needs, expectations and anxieties of the patient. Counselors neither recommend nor discourage a specific course of action. They work hard to give patients the most accurate interpretation of the test results and available options, enabling an informed decision. And nothing is held back.

“Whatever the results, we tell our patients regardless.” said Gima.

A “positive” result is not a guarantee that you'll get cancer, any more than a negative result guarantees you won't. So testing positive – even for high-risk BRCA gene mutations – should not necessarily mark a direct path to prophylactic surgery. Extra vigilance may be all that's needed. Chemoprevention with drugs like Tamoxifen may keep cancer at bay. And new, targeted therapies aimed at defective genes are being developed.
In fact, surgery may sometimes be the wrong choice.
“I think it's very bad practice,” Slavin said, “to operate on a 75-year-old woman who tested positive for a BRCA gene mutation, because we know that after menopause, the cancer risk goes down and she would only have a small chance to still develop a breast cancer. The risk surgery complications and pain are not worth the risk of a unlikely possible cancer.”
Some women however, when faced with that positive test panel, will inevitably insist on preventive surgery for their own peace of mind, as Ming did. 
“I didn't want to worry about it anymore,” she said.
Her decision, it turns out, was prophetic. After the surgery, pathologists examining the removed tissue did discover precancerous cells in the left breast. 
“I feel pretty lucky.”
(*To protect the patient’s privacy we've changed her name.)

If you are looking for a second opinion about your diagnosis or consultation about your treatment, request an appointment online or contact us at 800-826-4673. Please visit Making Your First Appointment for more information.


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