Columbia University Medical Center

Genetic Screening For Breast Cancer Genes May Improve Survival Rates For Those At High Risk

Ashkenazi Jewish women or women from high risk families with the two mutant breast cancer genes — BRCA1 and BRCA2 — may prolong their average survival by undergoing genetic screening, according to a mathematical model developed by researchers at Columbia University College of Physicians & Surgeons. The model evaluates the benefits of prophylactic mastectomy and oophorectomy (removal of the ovaries) to assess survival and quality of life. The study concluded that screening is a valuable preventive strategy, is cost-effective compared with the cost of other cancer screening tests, and should be covered by insurance companies. The findings were presented at the American Society of Clinical Oncology (ASCO) annual meeting.

Ashkenazi Jewish women with either BRCA1 or BRCA2 gene mutations have a 56 percent chance of developing breast cancer and a 16 percent chance of developing ovarian cancer by the age of 70. “Genetic testing makes sense for Ashkenazi Jewish women if those who test positive are willing to take appropriate action,” says Victor R. Grann, M.D. MPH, director of health outcomes research at Columbia-Presbyterian’s Medical Center’s Herbert Irving Comprehensive Cancer Center and lead author on the study. “Appropriate action might be prophylactic surgery, it might be more careful surveillance, or it might be enrollment in new studies to look at new drugs such as tamoxifen to see if these are effective in protecting them from getting breast cancer.”

In previous studies, Dr. Grann and colleagues looked at alternative treatments available for women who were tested for BRCA1 and BRCA2 to see what kind of decisions they would make in terms of prophylactic surgery or follow-up monitoring. Using a decision analysis model researchers looked at survival benefits, quality of life benefits, and cost effectiveness. Treatment options for women who tested positive include increased surveillance — frequent mammograms, physicals, and gynecological exams —or prophylactic surgery, which would include prophylactic mastectomy, prophylactic oophorectomy, or both procedures. Researchers found that for a 30-year-old woman with the BRCA1 gene who comes from a high-risk family, having both procedures — prophylactic mastectomy and oophorectomy — can prolong life expectancy by approximately six years, but at a great cost to quality of life. The researchers measured the effect of the three interventions on quality-adjusted-life- years, a common statistical measurement that attempts to take into account the impact of disease and treatment on daily happiness, self-image and physical comfort, for example. They found that a woman living with the physical and emotional effects of having her breasts and ovaries removed at age 30 gained only one quality-adjusted-life-year compared to a woman who chose not to have the procedures. A quality adjusted-life-year is defined as one year of perfect health.

The study presented at ASCO evaluated genetic screening to determine if it may be worthwhile from a health policy perspective and how it would affect this high risk population. Dr. Grann and colleagues developed a second model to evaluate screening for these genes among Ashkenazi Jewish women. The researchers report that a 30-year-old Ashkenazi Jewish woman has a 2.5 percent chance of carrying the BRCA1 or BRCA2 breast cancer genes. Researchers found for those who test negative there is no survival benefit to screening, but, there may be a quality of life benefit because of the tremendous relief of knowing they don’t carry the cancer genes.

For the 2.5 percent of Ashkenazi women who test positive, depending upon treatment choices they make, researchers used the decision analysis model to conclude that they could live a longer period of time. If they had both prophylactic surgeries they could prolong their lives by 4.2 years; prophylactic mastectomy alone would add 3.6 years. Prophylactic oophorectomy would add 1.2 years and surveillance would add .7 years over women who were not screened. The study showed that genetic screening offers a survival benefit for the entire tested group compared with a the non-tested group, and screening is very cost-effective.

“The cost benefits associated with genetic screening for Ashkenazi Jewish women or those at high risk compares to other cancer screening tests such as mammography and pap testing or other cancer gene testing,” says Dr. Grann. “From an insurance point of view it is the same cost-effective ratio as women who have mammography or pap smears so it actually makes sense to have women screened if they want to be screened and are willing to take appropriate actions if they test positive.”

According to Dr. Grann the downside is that if you are at high risk for cancer you may not get cancer although the risk may be more than 50 percent, that risk may not occur for 20 or 30 years. “The most important finding is that you do increase survival by screening–but you have to consider the procedures and options now,” says Grann. “If Ashkenazi Jewish women are tested they can increase their survival over women who aren’t tested in the same sort of fashion that women who have a mammography in the 50-69 age group can.” Grann cautions that this study is a mathematical model and that no actual study was performed on patients. “Given all the options, women have to reach their own personal decisions and evaluate their own choices,” he says. ###

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