A population-based genetic screening protocol is currently the only feasible way to gain prior knowledge of BRCA mutation status in asymptomatic carriers with unrevealing family histories.
Evanston, IL (Vocus) July 16, 2009
A group of researchers, led by a medical genetics expert at NorthShore University HealthSystem (NorthShore), is calling on medical professionals, public health leaders and the public to initiate a dialogue about the importance of establishing a population-based genetic screening program to help identify women who are unknowingly at high risk for ovarian cancer. The author's screening model analysis currently appears online in Genetics In Medicine, the official journal of the American College of Medical Genetics.
BRCA1 and 2 (BRCA stands for Breast Cancer) are genes that, when inactivated through mutations, place women at high risk for developing breast or ovarian cancer. Previous screening studies indicate about half of BRCA carriers may be unaware they have BRCA gene mutations because there is no family history of breast or ovarian cancer.
"If a woman does not know her genetic status, then she cannot take the necessary actions to reduce potential life threatening risks," said Wendy Rubinstein, M.D., Ph.D., lead researcher and director of the Center for Medical Genetics at NorthShore. "A population-based genetic screening protocol is currently the only feasible way to gain prior knowledge of BRCA mutation status in asymptomatic carriers with unrevealing family histories."
The researchers, however, stress that their screening model should serve as a starting point for people to engage in a dialogue about genetic screening and to provide appraisal of the proposed model's structure, function, applicability, societal impact, and cost and life-saving outcomes.
The model focused on the Ashkenazi Jewish population because the prevalence of mutations is higher than in the general population and the presence of specific "founder mutations" provides for a less expensive genetic screening test. The target group was post-childbearing Ashkenazi Jewish women (ages 35-55) in the U.S., numbering about one million women.
"Although the BRCA genes are generally apparent in relatively large families with many females in whom medical information is known and shared, not all families fit this bill," said Rubinstein.
"BRCA gene mutations may be masked in families that are small, have many males and few females, where there were early deaths from non-cancer causes or medical details are unknown, inaccurate, or not freely shared. So we cannot always accept the report that a family's history is negative as proof that they are not carriers," added Rubinstein.
The model also focused on ovarian cancer. Unlike breast cancer screening via mammography and MRI, ovarian cancer has no effective screening mechanism. Ovarian cancer also is generally more lethal than breast cancer because it is usually detected in advanced stages.
The researchers determined three outcome measures: the proportion of ovarian cancer diagnoses prevented by the program (cancer incidence), the number of quality-adjusted life-years gained or QALY (life expectancy) and the discounted cost of the program per QALY (cost). They were conservative in their assumptions about the risk of cancer to mutation carriers and the uptake of risk-reducing surgery, factoring in individuals' choices and decisions they might take if they were found to be carriers. The measures were averaged out on a per-person basis (in the total population) and applied to the target group.
Researchers concluded that their genetic screening program would theoretically result in 2,811 fewer cases of ovarian cancer, with a life expectancy gain of 1.83 quality-adjusted life-years among carriers. At a cost of $460 for founder mutation testing, the cost of the program would be $8,300 (discounted) per year of quality-adjusted life years.
The results prompt several societal questions such as what constitutes an acceptable cost to society for life saving strategies and what number of lives saved is sufficient to merit public health intervention, considering society ultimately would pay for the screenings.
"We must take into account that some women will benefit tremendously from the screening and most will not," noted Dr. Rubinstein. "But genetic screening must also be compared to other health interventions that have become life-saving, acceptable and promoted practices within our society."
For example, a 2005 published study concluded the cost-effectiveness of mammography screening (breast) is between $10,000 and $25,000 of quality adjusted life-years (QALY), implantable cardioverter-defibrillators (heart) is between $30,000 and $85,000 QALY and dialysis in end-stage renal disease (kidney) is between $50,000 and $100,000 QALY.
The researchers conclude that these are pertinent benchmarks with which to compare a life-saving and cost-effective genetic screening program. The cost of genetic testing ($8,300 QALY) appears to be well balanced by the benefits of avoiding a diagnosis of ovarian cancer and its treatment.
"Again, our analysis should serve as a catalyst to engage everyone in a dialogue about whether or not genetic screening is desirable, given our findings that suggest it would save lives at an acceptable economic cost," concluded Dr. Rubinstein.
The abstract is titled "Cost-Effectiveness of Population-Based BRCA 1/2 Testing and Ovarian Cancer Prevention for Ashkenazi Jews: A Call for Dialogue."
About NorthShore University HealthSystem
Headquartered in Evanston, Ill., NorthShore University HealthSystem (NorthShore) is a comprehensive, fully integrated, healthcare delivery system that serves the greater North Shore and northern Illinois communities. The system includes four Hospitals - Evanston Hospital, Glenbrook Hospital, Highland Park Hospital and Skokie Hospital. In addition, the health system has more than 2,400 affiliated physicians, including a 600-physician, multispecialty physician group practice with over 70 office locations - NorthShore University HealthSystem Medical Group. Further, NorthShore is committed to excellence in its academic mission and supports teaching and research as the principal teaching affiliate for the University of Chicago Pritzker School of Medicine.
The NorthShore University HealthSystem Research Institute focuses on clinical and translational research, including leadership in outcomes research and clinical trials. The NorthShore University HealthSystem Foundation is a leading philanthropic entity of NorthShore. It raises charitable contributions, engages volunteer friends and invests in community partnerships.
NorthShore has annual revenues of $1.5 billion and a staff of more than 8,000. The HealthSystem has significant capabilities in a wide spectrum of clinical programs, including cancer, heart, orthopaedics, high-risk maternity and pediatrics. NorthShore is a national leader in the implementation of innovative technologies, including electronic medical records, (EMR). In 2003, the HealthSystem was among the first in the country to successfully launch a systemwide EMR with demonstrable benefits in quality, safety, efficiency and service to patients. NorthShore has been recognized by multiple national organizations for this notable achievement.
CONTACT: Jim Anthony
Director, Public Relations
CONTACT: Rikki Ragland
Director, Public Relations
# # #