In the past 50 years, advances in medical research have greatly reduced death rates from heart disease, stroke and infectious disease. Unfortunately, breast cancer deaths have not dropped dramatically over the same period. Every year, more than 200,000 women are diagnosed with breast cancer in the United States. Of that number, almost 40,000 will die.
One of the main reasons cancer death rates have stayed the same is because scientists still don't understand the molecular changes that turn a normal cell into a cancerous one, said Lawrence Brody, Ph.D., chief of the Genome Technology Branch and senior investigator of its Molecular Pathogenesis Section at the National Human Genome Research Institute (NHGRI). His lecture - An introduction to genomics: breast cancer genes, risk assessment and screening - was the second of the seven-lecture series, Genomics in Medicine, held Jan. 6, 2011, at Suburban Hospital in Bethesda, Md. The lectures, which will be held monthly through July 2012, are sponsored by NHGRI in collaboration with Suburban Hospital and the Johns Hopkins University School of Medicine.
"In breast and ovarian cancer, we hope that a detailed understanding of the genes involved will lead to improvements in its prevention, early detection and prognosis and allow us to chose treatments that are tailored to a specific person's disease," said Dr. Brody, noting that cancer is produced by a combination of inherited and acquired genetic changes. His talk focused on the inherited factors that influence a person's risk of breast cancer.
In 1994, Dr. Brody's laboratory was among the first to report that women carrying mutations of the BRCA1 or BRCA2 genes have a much higher risk of developing both breast and ovarian cancer - a 50 to 80 percent increased risk of breast cancer over a lifetime - than women without these mutations. A year later, Dr. Brody's lab was the first to report that specific variants in BRCA1 and BRCA2 were found at a high frequency in Ashkenazi Jewish individuals. Since then, his group has created an online catalog of more than 2,000 distinct BRCA1 and BRCA2 mutations. Dr. Brody and others have used this information to better understand the range of cancer risk associated with these genetic mutations.
"BRCA1 and BRCA2 genes are DNA repair proteins that, when functioning properly, repair breaks to the double strand of the DNA helix or destroy cells if the DNA cannot be repaired. Cells cannot tolerate many double strand breaks," Dr. Brody said. The genetic mutations increase the risk of breast cancer because the cell loses its ability to repair the DNA or destroy cells if necessary, he explained. In individuals who carry BRCA1 or BRCA2 mutations, physicians recommend early cancer screening, more frequent screening and sometimes prophylactic surgery, he said.
While BRCA1 and BRCA2 mutations are uncommon a number of common genetic variants also contribute to breast cancer risk in the general population. In the future, this knowledge could be used to more efficiently screen women for breast cancer.
"If you could screen the 20 percent of people who are most at risk for [inherited] breast cancer, you would find 60 to 70 percent of all people with breast cancer," Dr. Brody said. "This is not something we're ready to do. But if you're going to use rare or expensive resources, eventually you might want to use the genetic risk profiles to guide your decisions."
Understanding what genes do has influenced the way we target these tumors and has enabled us to rationally design drugs to treat tumors, he said. Experimental data now show that drugs that target the DNA repair machinery, called PARP inhibitors, can specifically kill tumor cells that have lost BRCA1 or BRCA2 activity. These PARP inhibitors have minimal side effects and might be useful as a specific therapy for tumors that arise in the BRCA1 and BRCA2 carriers. PARP inhibitors are currently being tested in a number of breast and ovarian cancer clinical trials.
Stanley Lipkowitz, M.D., Ph.D., from the Laboratory of Cellular and Molecular Biology, National Cancer Institute, will deliver the next lecture, An introduction to genomics: breast cancer diagnosis and treatment, on Feb. 3, 2012. Dr. Lipkowitz will describe the genomic characterization of breast cancer as currently used in the clinic to define breast cancer subtypes, stratify risk and determine treatment. He will also discuss how these are likely to impact the future management of breast cancer.
Each lecture takes place at Suburban Hospital's lower level auditorium at 8600 Old Georgetown Road in Bethesda, Md. All are welcome to the hour-long lectures, which begin at 8 a.m. on the first Friday of the month, from December 2011 through June 2012.
Advanced registration is not required; however, those requesting continuing medical education (CME) credits are asked to sign in. For more information about the Genomics in Medicine lecture series, please contact Susan Laine at Suburban Hospital, firstname.lastname@example.org, or Alice Bailey at NHGRI, email@example.com.
Last Updated: March 15, 2012