In the mid-1990s, scientists for the first time were able to isolate and clone the BRCA1 and BRCA2 genes, mutations in which were thought to increase susceptibility to early onset breast and ovarian cancers. A new Perspective published last week in Science takes a look back at the last twenty years to show how the identification of these genes set in motion a firestorm of research aimed at exploring how genetic information can be used to create both standards of care and strategies for all patients at a high-risk of developing cancer. Much has been learned over the last twenty years and now, Penn Medicine’s Basser Research Center for BRCA - the first and only comprehensive BRCA-focused center of its kind – is at the forefront of the next generation of research about genetics and cancer risk, methods for risk reduction and prevention, and new cancer treatment therapies.
BRCA: Then and Now
Information gleaned over the last twenty years combined with new details about non-BRCA1/2 genetic variations is arming physicians and researchers with the tools to begin to developing models that will provide personalized care plans for BRCA1/2 mutation carriers based on genetic changes. Two decades ago, studies confirmed the association between BRCA1 and BRCA2 mutations and early-onset breast cancer and ovarian cancer. Since then, more than 1,800 distinct variants of BRCA1 and more than 2,000 of BRCA2 have been reported. Further studies revealed that not only are BRCA1/2 mutations hereditary, but some variations are also common among distinct populations. The best known example is in the Ashkenazi Jewish population, in which nearly three percent of individuals carry a mutated version of the gene. That means they have a 1 in 40 chance of carrying a BRCA1 or BRCA2 gene mutation -- a ten times greater probability than that of the non-Jewish population.
“A woman’s risk of breast cancer is still very much tied to family history, but it’s not just about their mother or grandmother; it’s about their father and his family history, too, and the population groups an individual’s family belongs to,” said Katherine Nathanson, MD, associate professor of Medicine in the Division of Translational Medicine and Human Genetics, co-leader of the Cancer Prevention and Control Program at the Abramson Cancer Center, and a co-author on the new Perspective. “Twenty years of research has provided a lot more information about these risk factors which helps us to more effectively counsel patients about their own cancer risk and possible preventative strategies.”
Today, BRCA1 mutation carriers are generally estimated to have a 57 percent chance of developing breast cancer and a 40 percent chance of developing ovarian cancer by age 70, whereas BRCA2 mutation carriers are estimated to have a 49 percent chance of breast cancer and an 18 percent chance of ovarian cancer.