NEW YORK (GenomeWeb) – A seven-gene test for breast cancer risk could be cost-effective in improving life expectancy among women with a family history of disease, according to a new study from Quest Diagnostic researchers.
While pathogenic variants within the BRCA1 and BRCA2 genes account for some 15 percent of familial breast cancer risk, variants in other genes like PALB2 and PTEN also contribute to that risk. Women with pathogenic PALB2 variants have between a 33 percent and 58 percent chance of developing breast cancer by the age of 70. By comparison, women with a pathogenic BRCA1 variant have a 65 percent chance of developing disease.
In a study published in this month's Value in Health, Quest's James Devlin and colleagues modeled whether multi-gene testing, rather than solely testing for BRCA1 or BRCA2 variants, could be cost-effective in increasing life expectancy among women with a family history of breast cancer.
The cost-effectiveness of wider screening has been a common topic of debate.
"This analysis suggests that genetic testing using next-generation sequencing of a seven-gene panel followed by risk-reduction procedures recommended by the [National Comprehensive Cancer Network] guidelines could extend life expectancy of women at risk of hereditary breast cancer at an acceptable cost," Quest's Devlin and his colleagues wrote in their paper.
Their model compared BRCA1 and BRCA2 testing alone to a multi-gene panel that tested for variants within the BRCA1, BRCA2, TP53, PTEN, CDH1, STK11, and PALB2 genes.
Under this model, women who tested positive for a pathogenic variant in any of these genes were assumed to have received genetic counseling and to have followed NCCN breast cancer risk-reduction guidelines. Those guidelines advise at-risk women to undergo increased surveillance via MRI as well as recommend risk-reducing mastectomy. The model also assumed that women who tested positive through the multi-gene panel would choose a prophylactic mastectomy at the same rate that women with BRCA1 or BRCA2 mutations do.
Additionally, the researchers estimated women's probabilities of developing cancer based on previously reported cumulative cancer risks and estimated the cost of surveillance, surgery, and other care from Medicare fee schedules as well as other cost reports.
For a hypothetical cohort of 50-year-old and 40-year-old women with a heightened risk of breast cancer, the model found that the seven-gene test approach could yield an incremental cost-effectiveness ratio (ICER) of $42,067 and $23,734 respectively, per life-year gained, as compared to BRCA1 and BRCA2 testing alone.
Likewise, the ICER for the seven-gene test strategy was $69,920 per quality-adjusted life-year (QALY) gained for the 50-year-old cohort and $48,328 per QALY gained for the 40-year-old cohort.
At this ICER level, the researchers said that the seven-gene test approach would be considered cost-effective under World Health Organization guidelines.
By comparison, they noted that an annual MRI for high-risk women was estimated to have an ICER of $179,600 per QALY gained.
However, the researchers noted that their model is based on a number of assumptions, including that breast cancer patients with pathogenic variants have the same risk of dying as breast cancer patients without such variants and that carriers of pathogenic variants in those five added genes all had same risk of disease as PALB2 carriers. Additionally, they noted that some women who test positive might chose to not undergo or delay prophylactic surgery.
Still, the researchers argued that their findings suggest that seven-panel gene testing is cost-effective for high-risk women.