Study Supports Cost-Effectiveness of Genetic Screening to Prevent Ovarian Cancer

Jacquelyn K. Beals, PhD

October 29, 2007 (San Diego) — Population testing of Ashkenazi Jewish (AJ) women for BRCA1/2 has the potential to prevent ovarian cancer (OC), prolong survival, and save nondiscounted costs of screening, according to an analysis presented here at the American Society of Human Genetics 57th Annual Meeting. Although current guidelines recommend BRCA1/2 testing if there is a positive family history, they do not recommend screening of all AJ women.
The poster cited studies showing that family history fails to identify half the women who carry the mutations and broke down the health and cost benefits of extending BRCA1/2 testing to the entire population of AJ women. Three founder mutations are responsible for 10% of breast cancers and 30% to 50% of OCs in this population.
Wendy S. Rubinstein, MD, PhD, FACMG, medical director, Center for Medical Genetics, Evanston Northwestern Healthcare Research Institute, Illinois, and lead author of the study, talked with Medscape Pathology about the decision analysis and its significance:
"If you start with an unselected group of women, you don't know what their family history is, but [if] they have ovarian cancer and they're Jewish, and then you test for the founder mutations, you'll find about 30% to 50% have that cancer due to an inherited tendency," said Dr. Rubinstein. "It's a very high proportion, it's not seen at that rate in very many other populations."
Values used for the decision analysis were drawn from research literature and included screening program participation rate, 0.9; mutation carrier rate in the population, 0.025; probability that a 40-year old carrier will follow up with a bilateral prophylactic salpingo-oophorectomy (BPSO), 0.50; probability that a mutation carrier will not get OC after PBSO, 0.96; probability that a mutation carrier will not get OC without PBSO, 0.84; probability that a noncarrier will develop OC, 0.016.
Additional parameters included in the analysis were the probability that women would get screening in the absence of a screening program and the proportion of carriers among women screened independently.
Dr. Rubinstein noted: "People that can find their way to clinics that do primary BRCA1/2 testing are knowledgeable. They usually have a high socioeconomic status, they usually have insurance, access to the types of screening that would be entailed to preventive measures. That means that there's a whole group of people who don't know, who aren't referred, and can't avail themselves of this.
"Education about your family history, that's where most people focus their efforts, and that's very appropriate," she continued. "The point is, that approach may miss a very significant number of individuals.... I don't know that it's a matter of access so much: Access implies that you know you have a problem but you can't get care for it. This is more an issue of awareness."
The analysis predicted that population-based BRCA1/2 screening in the AJ population would increase average survival by approximately 384 days for a 40-year old AJ woman BRCA1/2 carrier who had PBSO and would save about $100 in nondiscounted costs for each woman screened. The latter figure was based on the commercial cost of testing for the 3 founder mutations, $460; the cost of PBSO, $4622; the cost of OC treatments, $55,323; and the cost of follow-up care and last-year-of-life care.
Dr. Rubinstein commented on the challenges of dealing with health issues in a particular ethnic group: "The issue that I'm starting with is: Would it be cost effective to do this approach...would it save lives? It's very different than saying it should be done, because there are many other societal issues that have to be dealt with. When you're dealing with an ethnic group of any kind, you want them to have a stake in this rather than just saying "oh, yes, it's obvious this should be done."
Sharon Plon, MD, PhD, associate professor of pediatrics, director of Baylor Cancer Genetics Clinics and Neurofibromatosis Clinic, Texas Children's Hospital, Baylor College of Medicine, Houston, also talked with Medscape Pathology about population-based screening.
"It's a subject that I've studied for many years, and I think it's very important to really consider the ramifications of doing population-based screening...," Dr. Plon said. "Looking [at] the cost-effectiveness and some of the ongoing studies in Israel I think will hopefully get enough data to finally answer the question.... Even though those are not the current recommendations of the groups that put out guidelines..., I think that there [are] increasing data that it is probably worthwhile to do it."
Dr. Rubinstein reported an association with the speakers' bureau of Myriad Genetic Laboratories, Inc.
American Society of Human Genetics 57th Annual Meeting: Abstract 419/F. Presented October 26, 2007.