Garnet Anderson, PhD  - Fred Hutchinson Cancer Research Center

Susan Johnson, MD – University of Iowa

A risk model is being developed (similar to the Gail model for breast cancer) that incorporates serum markers of risk as well as epidemiologic risk factors.  The primary objective is to develop and validate a risk model to estimate a woman’s probability of developing ovarian cancer during a defined interval such as 5 years.

The project follows our general strategy in meeting translational research goals, which includes 1) exploitation of emerging molecular technologies to identify biologically relevant genes and proteins as candidate markers for use in risk prediction, 2) a systematic approach to prioritizing markers for evaluation, 3) a collaborative approach to evaluating candidate markers that includes evaluation of candidates identified by colleagues at other institutions, and 4) use of novel statistical methods to use markers to predict cancer diagnosis.  Project investigators have progressed beyond discovery and prioritization and are poised for validation and clinical use within the next 5 years.

Early detection and prevention hold great promise for reducing the morbidity and mortality of ovarian cancer.  Though the disease is rare, thousands of women are diagnosed with ovarian cancer each year, and most will die of it because their tumors are found in advanced stages where despite years of research, survival rates remain stubbornly low.  If developed, an accurate screening method could shift the stage of disease and, it is hypothesized, the overall prognosis. 

A risk estimation procedure is needed to allow us to identify high risk women both for prevention research and for identifying subsets of women for whom the risks and potential benefits of screening may be justified, possibly even with the imperfect technologies currently available.

There is growing interest in developing screening and prevention techniques for ovarian cancer.  The final evaluation of any screening or preventive intervention will require a randomized trial.  To achieve adequate power, the expected incidence will need to be at least in the hundreds of cases. Unless we can target truly high-risk women, the sample size of such a trial will be in the tens of thousands and the feasibility of such a trial is doubtful.  Similarly in screening for ovarian cancer, the available technologies are not sufficiently accurate to justify use in a general population.  The risks of false-positive results, both in psychological costs and in unnecessary surgeries, are too high for routine use. Women are now classified as high risk if they have a family history of ovarian cancer or their family history suggests an underlying BRCA1 or BRCA2 mutation.  While family history is important for etiological considerations, its use for screening or prevention trial planning is limited by the fact that its attributable risk is only 3%.  For postmenopausal women, the use of serum markers as well as epidemiologic indicators of risk may significantly improve the risk estimation procedure.