Common Genetic Mutation in Breast Cancer May Point to New Treatments for Heart Disease

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A genetic mutation implicated in breast and ovarian cancers could also have a role in causing heart failure, according to a new study reported at the 95th annual Clinical Congress of the American College of Surgeons.

The researchers, led by Subodh Verma, MD, PhD, FRCSC, FAHA, report that mutation of the BRCA1 gene, long linked to breast cancers, also disrupts the normal replacement cycle of heart muscle cells in laboratory mice. This is the first time such a link has been reported. The study team from St. Michael’s Hospital in Toronto, the University of Toronto, and Imperial College London, concluded the findings may not only help pursue new treatments for heart disease, but may have more immediate implications for cancer patients undergoing treatment.

“This [finding] suggests the people who carry the BRCA1 mutation may have an excess mortality over their lifetime that cannot be explained by cancer-related death,” according to Dr. Verma, a cardiac surgeon at St. Michael’s Hospital, associate professor of surgery and pharmacology at the University of Toronto, and the Canada Research Chair of Atherosclerosis.

Heart disease kills approximately 900,000 Americans each year, while doctors diagnose approximately 200,000 new cases of invasive breast cancer a year; 40,000 of those women die each year from the disease. Previous studies have shown that mutations of the BRCA1 and BRCA2 genes are found in 40 percent of families, and that mutation in the BRCA1 gene posed up to an 85 percent lifetime risk of developing breast cancer. The researchers in Toronto focused on the BRCA1 gene only.

Some of the chemotherapy drugs commonly used in breast cancer, including doxorubicin, can also harm the heart and surrounding tissue. “People who have cancer syndromes because of not having the BRCA1 gene may also be highly susceptible to the cardiac toxicity of the chemotherapy that they are receiving,” Dr. Verma explained. “In some ways, this finding may help define what kind of chemotherapy such an individual should get.”

The study may also point to new factors in the treatment of heart disease. “For millions of people in the world who have heart failure, repairing DNA may be very important, especially for younger people with heart failure that may be terminal,” Dr. Verma said.

The study also linked the BRCA1 gene to development of Atherosclerosis, or hardening of the arteries. “Cardiac infarction and heart failure represent the world’s number one killer, and finding that a cancer gene may be implicated in both heart failure and cardiac infarction/ Atherosclerosis is a very important observation,” said Dr. Verma.

The study authors have started to investigate the incidence of BRCA1 gene mutations and heart disease in human population databases. However, clinical trials of BRCA1 gene therapy in people with heart disease may be at least two years away.

In addition to Dr. Verma, Praphulla C. Shukla, PhD; Krishna K. Singh, PhD; Fina Lovren, PhD; Yi Pan, MD; Howard Leong-Poi, MD; Lee Errett, MD; William L. Stanford, PhD; Michael D. Schneider, MD; and Thomas G. Parker, MD, participated in the study.

Source:  American College of Surgeons (ACS)

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