BRCA1/2 and Other Genes Associated with Breast and Ovarian Cancer: The Importance of Genetic Testing
Most cancers are not inherited. Only about 5 percent to10 percent of breast cancers and 10 percent to 20 percent of ovarian cancers are hereditary, due to at least one genetic change that significantly contributes to the risk of developing cancer. Among the mutations – and linked to both types of malignancies – are BRCA1 and BRCA2, genes that produce tumor-suppressor proteins, which help repair damaged DNA and play a role in ensuring the stability of a cell’s genetic material. When either of these genes is altered or fails to function correctly so that its protein is not made, damage to DNA can’t be repaired properly. As a result, cells are more likely to develop additional genetic alterations that can lead to cancer.
"BRCA1 and BRCA2 were first sequenced in 1995 and 1996 and are key factors in predicting breast and ovarian cancer risk, but it’s also important for healthcare providers to know that there are at least 17 other genes that can increase the risk of both cancers,” says Kathryn Mraz, MS, CGC, certified genetic counselor with the Cancer Risk Genetics Program at the Memorial Hermann Cancer Center-Texas Medical Center and McGovern Medical School at UTHealth. “Because we haven’t tested many of these genes for as long a period of time as we’ve tested BRCA1/2, we haven’t quantified the associated risk for many of them. Basically, predicting the risk of developing breast or ovarian cancer is no longer as simple as having a mutation in either BRCA gene.”
BRCA genetic testing has improved over the years. “In the early years we just did sequencing, which is like a spell check for genes that picks up 85 percent of the mutations,” Mraz says. “Since 2008 we’ve had the capability to check for large genetic deletions and duplications, which gives us a big-picture view. Compared to spell check, this is more like proofreading for sense to make sure that things are not out of order, and it picks up 10 to 15 percent for BRCA1/2 carriers. Around 2012, it became a combined test. So patients who had negative results on a test for a BRCA1/2 mutation in 2007 haven’t really been comprehensively tested.”
Specialists at the Cancer Risk Genetics Program see between 25 and 40 patients each month, including new patients and those who return in follow-up. They meet with Mraz and a medical oncologist to discuss cancer risk assessment; if their personal or family history is suggestive of a hereditary cancer syndrome, they are offered genetic testing, if available.
They also discuss ways to help lower cancer risk or take preventive measures on a personal level. A team of experts develops a personalized cancer surveillance plan for each patient’s needs and helps them navigate their care. They also address the cancer risk of family members and make recommendations for evaluation and testing.
“Genetics is a rapidly advancing field, and we have to keep up with the literature,” Mraz says. “If we find either BRCA1 or BRCA2 or a lower-risk gene to be mutated or not working, we follow National Comprehensive Cancer Network (NCCN) recommendations for BRCA-related cancer risk in addition to considering updated literature. We also follow each of these patients in our clinic. Maybe a woman just had breast surgery and hasn’t yet made plans for ovarian cancer risk management, is a candidate for high-risk pancreatic surveillance or has family members who would benefit from testing and she wants to learn more about their options. It’s a lot to deal with, and I help them navigate the process by providing information. We make recommendations about how to proceed so that they can make informed choices.”
Genetic Counseling Testing: When Is It Recommended?
Genetic counseling can be appropriate for individuals and family members who want to make informed decisions to assess their risk and plan for the future.
Counseling is recommended for anyone with a diagnosis of cancer at age 50 or younger; anyone who has been diagnosed with two or more primary cancers; anyone with a diagnosis of one or multiple rare cancers or discovery of a rare tumor; anyone with more than one close family member diagnosed with either the same type of cancer or related cancers – for example, breast, ovarian and/or pancreatic cancer or colon and endometrial cancer; anyone with multiple family members with cancer; anyone with more than 10 colon polyps over their lifetime; anyone of Ashkenazi Jewish ancestry with a personal or family history of breast, ovarian, prostate or pancreatic cancer; anyone who has previously undergone genetic testing through a physician and wants to learn more about the results; anyone considering genetic testing or inquiring about information for a family member; anyone at high risk, with or without a known cancer susceptibility syndrome, who has questions about cancer prevention, screening options or treatment; and anyone who is concerned about their personal or family’s cancer risk, regardless of high-risk status.
Physicians need to provide a referral to the Cancer Risk Genetics Program at Memorial Hermann-Texas Medical Center. Patients may also contact Kathryn (Kate) Mraz directly at 832.325.7206 to learn more about the process.