The field of genetic testing for cancer is rapidly evolving. Veda N. Giri, MD, the new Chief of the Division of Clinical Cancer Genetics at Smilow Cancer Hospital and Yale Cancer Center is at the evolution’s forefront. The field’s dynamism excites her, and she has ambitious plans for a novel, comprehensive program at Yale.
“I’m a medical oncologist by training,” Dr. Giri said, “and I’ve always had a deep interest in treating patients and in cancer risk assessment. Cancer genetics marries those two interests. Genetic testing has become central for informing us about better strategies for treating patients who carry specific genetic mutations, tailored cancer screening, and hereditary cancer assessment for patients and their families.”
Dr. Giri joined Yale from Thomas Jefferson University, where she was director of Cancer Risk Assessment and Clinical Cancer Genetics since 2014. While the field of genetic testing has been grounded in assessing hereditary cancer risk, the field of precision medicine has skyrocketed the volumes of patients needing genetic testing to inform cancer treatment.
“Patients and providers are increasingly interested in thinking about what genetic tests should be done to inform decisions about cancer treatment,” said Dr. Giri. For example, multiple PARP inhibitors have been approved for use in the treatment of patients with a variety of cancers who carry mutations in DNA repair genes, such as BRCA1 or BRCA2, due to clinical responses. As such, patients may be referred for genetic testing to inform cancer treatment, but it still requires that patients understand hereditary cancer risk, which can be uncovered by genetic results.
Genetic evaluation requires that patients receive information to make an informed decision for genetic testing. Since germline testing involves uncovering hereditary cancer risk, the first step, she continues, is explaining basic heredity to patients: we inherit half of our DNA from each parent, and our genomes carry more than 25,000 genes. Genetic testing assesses genes of interest based on the cancer of concern and can also uncover additional cancer risks. For instance, a man with prostate cancer—one of Dr. Giri’s interests—may show a mutation in the BRCA2 gene, which signals risk not only for aggressive prostate cancer, but for pancreatic cancer, male breast cancer, and melanoma.
Cancer risks for females with BRCA2 mutations include pancreatic cancer, female breast cancer, ovarian cancer, and melanoma. Since this is hereditary cancer testing, children have a fifty percent chance of inheriting mutations, and the associated cancer risks.
“There is a ripple effect in families, since the genetic mutation should be tested in all blood relatives and inform tailored cancer screening,” said Dr. Giri. One key reason for genetic testing, she adds, is to inform cancer screening and prevention. If that man with prostate cancer passes on a BRCA2 mutation to his son, Dr. Giri would recommend that the son start screening for prostate cancer at age 40 instead of age 50, which is the recommendation for average-risk individuals. She also would discuss screening for pancreatic cancer especially if there is a family history of pancreatic cancer, and an annual clinical breast exam starting at age 35 for male breast cancer screening. If the patient’s daughter inherits the mutation, likewise, Dr. Giri would discuss screening for pancreatic cancer, and instead of an annual mammogram starting at age 40, Dr. Giri would discuss breast cancer screening starting at age 30 or younger based on family history of breast cancer with the addition of breast MRI. For females, the national guidelines also recommend risk-reducing surgery to remove the ovaries around ages 40-45 or after childbearing due to the higher risk for ovarian cancer in females who carry BRCA2 mutations.