Lifetime Burden of Inaccurate HER2 Testing

Chicago—Among the estimated 26,870 women who were diagnosed with breast cancer in 2012, 20% had tumors that overexpress the human epidermal growth factor 2 (HER2) gene, a marker of severity of disease that can influence therapy selection. All breast cancer patients should be tested for HER2 status, allowing their tumors to be identified as HER2-positive (HER2+) or HER2-negative, according to researchers.

Noting that HER2 testing may result in false-positive (FP) or false-negative (FN) results, researchers recently conducted an analysis to estimate the lifetime economic burden of inaccurate HER2 testing in the United States among the 2012 cohort of early stage breast cancer patients. They reported results of the analysis during a poster session at the ASCO meeting. The poster was titled The Lifetime Economic Burden of Inaccurate HER2+ Testing: Comparing False-Positive and False-Negative HER2+ Tumors in Early Breast Cancer Patients in the United States.

The consequences of a FN result include the loss of added life expectancy in life-years due to lack of targeted therapy, and an increased chance of recurrence and progression to metastatic breast cancer with associated healthcare costs. In addition, there is a savings of healthcare resources that would have been expended on HER2-targeted therapy.

An FP result may lead to the use of HER-2 targeted therapy with little chance of benefit, an increased risk of adverse events associated with HER2-targeted therapy, and the added cost to the patient, the payer, and society of HER-2 targeted therapy.

To estimate the probability of tumor misclassification as FP or FN and the associated health and economic consequences, the researchers developed a decision-analytic model. In the total cohort, the model found the individual patient probability of FP and FN misclassification was 2.8% and 2.2%, respectively.

The mean per patient costs of FP and FN misclassification were $56,800 and $118,000, respectively. Using 226,870 as the estimated number of incident early-stage breast cancer patients in a year, the researchers said there would be 6370 patients whose tumor was misclassified as HER2+ and 5046 who would be misdiagnosed as HER2-negative. This would result in $596 million due to FN misclassification and $363 million due to FP misclassification.

The total lifetime aggregate cost of HER2 inaccuracy in the United States would be $958 million, the researchers noted.

Limitations to the study cited by the authors include basing the model in the assumed rate of 20% of HER2 positivity, the lack of a determination or implication of an efficient remedy for HER2 testing inaccuracy, and the inability to generalize the results outside the United States.

In summary, the researchers said, “Current testing algorithms and treatment patterns for HER2+ early breast cancer result in misdiagnosis and nonoptimal treatment in approximately 11,500 patients each year in the United States: the combined total economic loss to society is nearly #1 billion. The greater share of the loss is among FN patients who would have benefited from trastuzumab, but did not receive it. The significant overall annual budget of HER2 misdiagnosis suggests that substantial investments to improve HER2 test accuracy should be considered.”

They added, “More research is needed on the cost-effectiveness of alternative testing strategies.”

Support for this study was provided by Genentech, Inc.