Population-wide screening of younger women for hereditary breast and ovarian cancer (HBOC) may be more cost-effective than broadly testing older women, according to a new study in JAMA Network Open. Women between the ages of 20 and 35, the researchers found, have more time to take action to prevent these diseases through prophylactic surgery compared to women older than 50. These results suggest that wide screening of younger women for HBOC should be considered both to prevent more cancers and to help more women at low risk of breast cancer to avoid unnecessary additional screening.
“Screening for genetic conditions and risks has become common for the perinatal period, but whether to do so for adults is still debated. This study adds to the growing literature that testing for common genetic risks, such as hereditary breast and ovarian cancer, early in adult life is beneficial to patients and cost-effective from a societal perspective,” said Josh Peterson, M.D., professor of Medicine and Biomedical Informatics, and one of four Vanderbilt co-authors of the study.
Hereditary HBOC genetic variants, particularly in the BRCA1 and BRCA2 genes, confer increased lifetime risk of developing cancer. Intensive precancer screening practices include magnetic resonance imaging (MRI) to detect cancer sooner, and some patients choose chemoprevention and/or prophylactic risk-reducing mastectomy (RRM) and/or risk-reducing salpingo-oophorectomy (RRSO), which lower cancer risk and mortality. However, many HBOC carriers are identified only after their first cancer diagnosis, often owing to a lack of knowledge or an unremarkable family history.
Genomic screening for HBOC has long been a matter of intense debate. Although the U.S. Centers for Disease Control and Prevention lists this genetic syndrome as a Tier 1 genomic application with “significant potential for positive impact on public health,” the U.S. Preventive Services Task Force guidelines for BRCA1/2 testing recommend against routine risk assessment for women without personal or family medical histories that suggest a genetic carrier status.
In this study, researchers developed a decision-analytic model to compare population screening for hereditary breast and ovarian cancer in an unselected population of previously undiagnosed women versus no screening. They then modeled clinical events in the decision tree. The risk variants included BRCA1, BRCA2, ATM, CHEK2, MSH6, PALB2, RAD51C AND TP53. Estimates were based on extrapolated data from the Geisinger MyCode Community Health Initiative and other published sources.
The results indicated that population screening of 30-year-old women resulted in 75 fewer cancer cases per 100,000 women. With 45-year-old women, the benefit decreased sharply with only 24 fewer cancer cases per 100,000 women. The researchers also analyzed quality-adjusted-life-years (QALYs) with the two scenarios and found that 288 QALYs were gained for women age 30 compared to 97 QALYs for women age 45.
The researchers also sought to determine if “cascade” benefits occurred when women identified at risk shared the information with relatives. They did not find that cascade screening fundamentally impacted clinical and economical values. Although 70% of carriers informed family members, only 20% of those relatives were assumed to undergo testing, which reflects the low rates of cascade testing uptake in practice. The researchers did, however, recommend that cascade testing be implemented where feasible.
This study is a product of the RISE (Rational Integration of clinical SEquencing) consortium, which seeks to estimate the long-term clinical and economic value of genetic screening scenarios. That information will be used to help increase diagnosis of genetic diseases, personalize preventative care, and tailor therapies based on genetic risks. The consortium’s members include Vanderbilt University Medical Center, the University of Washington in Seattle and Geisinger Health. It is supported with funding from the National Human Genome Research Institute.
David Veenstra, PharmD, Ph.D., professor of Pharmacy at the University of Washington, a principal investigator for RISE and associate director of Comparative Health Outcomes, Policy and Economics (CHOICE), is the corresponding author for this HBOC screening study, and Gregory Guzauskas, MSPH, Ph.D., a senior research scientist with CHOICE, is the first author.