By Dr. Lucio Miele, MD, Ph.D
Women should know only 5-10% of breast cancers are considered “familial” or resulting from inherited genes. Yet they should also know having a family history of breast cancer is one of the strongest predictors of breast cancer.
Women with two or more first-degree relatives (mother, sister, daughter) who have/had breast cancer are more than four times more likely to develop breast cancer than other women. Several gene variants strongly increase the risk of breast cancer, including the well-known BRCA1 and BRCA2 and at least 10 other genes. Tests to detect these variants can be performed on blood or saliva in individuals with significant family history of breast cancer.
In addition, there are many other genes which can affect the risk of breast cancer, but have smaller effects on individual risk, or are less commonly mutated. When someone with a significant family history of breast cancer is found to be negative for the most common genes, broader gene panels are available, called “exome panels”. These test hundreds or thousands of genes known to be involved in cancer risk that can potentially be passed on to one’s children.
Gene Makeup Helps Determine Medication Type
Another class of tests look at genes damaged within the cancer itself or genes “expressed” (active) within the cancer. These genes are not inherited. They are altered during the course of cancer development within the breast cells, but not the rest of the body. Gene expression tests performed on tumors are used to predict response to medications. There are three tests (Oncotype DX, PAM50 and Mammaprint/Blueprint) that predict the risk of recurrence and determine whether a patient with hormone receptor positive breast cancer (also known as “ER-positive” or “luminal” breast cancer) will need chemotherapy. Based on the score of these tests, physicians can determine whether hormone therapy alone is sufficient, thereby avoiding the side effects of chemotherapy. Other gene tests performed on cancer (cancer exome panels) look at which genes are damaged in the cancer itself. These too give information on how responsive a tumor may be to specific medications.
Genes Can Influence How Well a Medication Works
A final group of tests look at genes involved in metabolizing drugs. Different patients process medications with different efficiencies. This can affect the safety and efficacy of medications. Variants in genes that control the metabolism of many drugs are already known. These variants are called “polymorphisms”. They are normal, but differ between different people (such as eye color). The tests that study these genes are called “pharmacogenomics”. These tests can provide information to optimize the dose of certain drugs. Using genetic and other tests to optimize prevention and treatment is an application of “Precision Medicine”.