Cancer Genetics 101: What Your Patients Need to Know

Aimee Martin, MGC, CGC, Senior Genetic Counselor, West Cancer Center, presents during the 2022 West Oncology Conference - Updates for Advanced Practitioners and Nurses.

At this year’s West Oncology Conference for Advanced Patient Practicioners (APP) and Nurses, Aimee Martin, Senior Genetic Counselor at West Oncology, provided a brief overview of hereditary cancer genetics, reviewed the main indications for genetic testing in cancer, and discussed strategies for communicating testing results and their implications to patients.


She noted that most cancers (80 – 90%) are sporadic, and result from acquiring 2 somatic mutations, or mistakes within their gene copies, over time, which can result in cancer. Hereditary cancers, however, are less frequent (5 – 10%) and result from one inherited or germline mutation, and one acquired mutation, again resulting in 2 defective gene copies that result in cancer. She noted that (because one gene is already defective at birth) hereditary cancers often arise at a younger age in patients.


Some of the major red flags for suspecting a hereditary cancer are cancers that occur in the young (e.g., < 50 years), those that are rare, (e.g., pancreatic, male breast cancer), multiple cancers (e.g., 2 or more different cancers, or bilateral cancers, occurring in the same individual), having 2 or more family members with the same or related cancers, and specific pathologic types such as triple negative breast cancer, or certain types of colon or endometrial cancer, such as those with microsatellite instability (MSI).


She discussed the major hereditary cancer syndromes, including those related to BRCA1/BRCA2. These are tumor suppressor genes involved in DNA damage recognition and repair, and are implicated in multiple cancers including breast, ovarian, pancreatic, melanoma, and prostate. Management strategies for patients with BRCA1/BRCA2 mutations include surgical options, increased screening/surveillance, chemopreventitive measures, and systemic treatments. For example, breast cancer screening is indicated earlier in those with BRCA1/BRCA2 mutation, and surgical options such as prophylactic mastectomy, hysterectomy (TAH), or bilateral salpingo-oophorectomy (BSO) can reduce risk of developing breast and ovarian cancer in these individuals by >95%. Other genes related to hereditary breast cancer include TP53, PTEN, STK11, CDH1, and others which can confer a more moderately elevated risk, such as ATM, CHEK2 and PALB2.


She reviewed the role of Lynch Syndrome (LS) in hereditary colorectal cancer (CRC), which accounts for about 3% of all CRC. She noted that LS involves mutations in 5 genes which play a role in DNA mismatch repair, and as such the hallmark of LS is mismatch repair deficiency (dMMR) and microsatellite instability. The main risks for LS include CRC (up to 61%) and endometrial cancer (up to 57%) but also several other cancer types. As such, increased screening for CRC (colonoscopy) and interventions to prevent uterine and ovarian cancers (e.g. TAH/BSO) may be indicated for individuals with LS. There are a number of other rare inherited GI syndromes such as familial adenomatous polyposis (FAP) and juvenile polyposis, which may be suspected if patients have an excessive number of polyps, or specific types of polyps detected on colonoscopy.


She described the use of multi-gene panel testing in cancer, which currently involves screening dozens of genes involved in hereditary cancers and which can be performed using blood, saliva, cheek swabs, or skin fibroblasts. She noted that, depending on the type of gene panel, and/or the laboratory used, there may be a risk for uncertain results in up to 40%. She also described the different kinds of results that may be obtained with genetic testing, specifically, a positive result (whereby a variant has been detected that is associated with an increased cancer risk), a negative result (whereby no cancer-causing variant was detected), and an uncertain result (whereby a variant is detected that may or may not impact cancer risk). For positive results, additional screening or preventive measures may be needed, whereas for negative results generally no additional screening or preventive measures are needed unless family history should warrant it. Uncertain results (also known as variants of uncertain significance, or VUS) are generally considered not harmful, and no additional screening or preventive measures are indicated.


She also outlined the role of genomic testing of tumors, also known as somatic tumor profiling, in cancer treatment. These are tests which can identify specific mutations in tumors that can drive tumor growth, and this information can be useful to predict response to chemotherapy and whether patients are candidates for clinical trials. She noted that, while most mutations found with this type of testing are not hereditary, there are some such as BRCA1 or BRCA2 which can be, and genetic testing may be indicated if such mutations are found.


With regard to communicating genetic testing results to patients, she noted that it is important to do so in a timely manner (e.g., via the provider or a patient portal), especially if positive results are found; further follow up counseling should also be offered as an option with positive results. Also, if VUS are found, patients should be advised that there may further updates in the future and to check back on their testing results at 1- or 2-yearly intervals.


As a summary, she noted that genetic testing in cancer is a complex and evolving field, and that genetic counselors are available to offer guidance to patients. Genetic testing results, if positive may be useful to guide surveillance and/or preventive strategies not only for the patient, but also for the immediate family who may be at risk. In addition, genetic testing in tumors may be indicated as a means to help to guide treatment, but may also offer clues to as to whether a hereditary component is involved.


See more from the 2022 West Oncology APP here.

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