Abstract
The American Society of Clinical Oncology and the College of American Pathologists recommend that human epidermal growth factor receptor 2 (HER2)/neu status be determined for all invasive breast cancers. Although the most commonly used modalities to determine HER2/neu status, immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), generally give concordant results, a small but consistent discordance rate between them has been demonstrated in prior studies. Most institutions in the United States use a "reflex testing strategy" for determining HER2/neu status. In a reflex testing strategy, cancers are screened with IHC, and FISH is reflexively performed only if the IHC results are classified as equivocal. Other institutions perform both tests on all cancers to maximize diagnostic accuracy (dual testing strategy). The cost-effectiveness of dual testing and reflex testing strategies are comparatively assessed herein. A decision analysis model was established comparing these 2 testing strategies. Model probabilities were obtained from an institutional invasive breast cancer cohort. Quality-adjusted life-years (QALYs) and cost estimates were extracted from published literature. All costs were converted to 2018 US$ values using the consumer price index. One-way sensitivity analysis was performed, as well as probabilistic sensitivity analyses with acceptability curves. A total of 1247 consecutive invasive breast cancer specimens were tested with a dual strategy. By IHC, 65%, 28%, and 10% were negative, equivocal, and positive, respectively. By FISH, 87% and 13% were HER2/neu-negative and HER2/neu-positive, respectively. Six patients whose cancers were IHC-positive (3+) were found to be FISH-negative. These 6 represented 5% of the 119 cases with HER2/neu 3+ scores and 0.55% of the 1082 cases with HER2/neu-negative results by FISH. Sixteen (2%) of 809 cases with a negative IHC result were ultimately classified as HER2/neu-amplified by FISH. These 16 cases constituted 10% of all cases that were ultimately classified as HER2/neu-amplified by FISH. Overall, a reflex testing strategy was found to be less costly than a dual testing strategy ($44,470.99 vs. $45,908.86, respectively), but was also less effective (10.28 vs. 10.30 QALYs). The incremental cost-effectiveness ratio was $70,051.55/QALY. In conclusion, in this single institutional cohort of breast cancers, a dual testing strategy to determine HER2/neu status was found to be more cost-effective than a reflex testing strategy.