Closing the Personalized Medicine Information Gap: HER2 Test Documentation Practice | Page 4

Published Online: January 21, 2013
Ilia L. Ferrusi, PhD; Craig C. Earle, MD; Maureen Trudeau, MD; Natasha B. Leighl, MD; Eleanor Pullenayegum, PhD; Hoa Khong, MD; Jeffrey S. Hoch, PhD; and Deborah A. Marshall, PhD
Documented HER2 Testing Patterns

The quality and consistency of HER2 test documentation varied widely, but test type was distinguishable for 96% and 95% of first and second tests, respectively. Among tested patients, 95% had 1 or more IHC tests and IHC tests accounted for 94% of all first tests. Conversely, 15% of tested patients had 1 or more FISH tests, and 2% received FISH as the first test. The majority of patients (73%) had a single test documented. Secondary tests were noted for 24% of tested patients, while the remainder received more than 2 tests (3%). The second test type was split almost evenly among IHC and FISH at 49% and 46%, respectively. A maximum of 6 tests were noted for a patient across multiple pathology reports, which could not be ruled as duplicate reporting.


This study addresses a knowledge gap about HER2 test documentation and testing patterns in the largest cohort of female early-stage BC patients reported in the literature to date. In this population-based cohort, we documented a HER2 test for 66% of patients from pathology reports held by the Ontario provincial cancer agency within the context of a universal access environment where HER2 testing was standard practice for all early-stage patients.

Test documentation was related to documentation of other pathology factors such as hormone receptor testing, tumor stage, and histologic grade. Similarly, clinical measures of tumor pathology indicated that patients with more aggressive disease (advanced stage and grade) were more likely to have HER2 test documentation. Higher odds for testing in stage II or III versus stage I disease were expected given that some stage I tumors were likely smaller than 1 cm and therefore not indicated for trastuzumab treatment or HER2 testing. We also found that hormone receptor–negative patients were less likely to have HER2 documentation. We would expect the opposite trend, with hormone receptor negative–patients having a higher rate of documentation, if the potential clinical need for trastuzumab were a determinant of HER2 documentation. These findings do not suggest that patients with less aggressive disease lacked access to HER2 testing, but rather suggest that completeness of centralized reporting or documentation might be related to disease severity. That is more likely to be a function of the registry reporting system than of the clinical need for trastuzumab, as HER2 reporting for trastuzumab reimbursement is provided independent of the registry. However, the potential for residual confounding in the cohort limits our ability to draw conclusions about the role of disease severity in HER2 documentation. In contrast, HER2 test documentation was not related to sociodemographic factors such as urbanicity or income, or to comorbidity, consistent with the policies of the Ministry of Health and Long-term Care. These observations were robust across different modeling perspectives and sensitivity analyses.

Our multivariable analysis results both support and challenge the findings of other studies. A report from Nova Scotia, Canada, found that untested patients tended to be older and have smaller tumors.14 Similarly, a study in Swansea, Southwest Wales, also suggested that elderly patients were less likely to have HER2 testing.29 These age-related differences in HER2 testing and documentation are consistent with the results of the current study. A study of Kaiser Permanente Northwest patients found that HER2 testing was more common among those also tested for estrogen receptor status.30 That is consistent with documented practice in Canada, where HER2 and hormone receptor testing by IHC are typically conducted simultaneously in centralized laboratories.31 However, HER2 testing in the Kaiser Permanente population was lower in patients with Medicare or Medicaid insurance.30 This situation differs from that in Ontario, where HER2 testing is universally available, regardless of enrollment in either provincial or private insurance plans. Indeed, we demonstrated that sociodemographic factors did not play a role in test documentation. A recent analysis of early-stage BC in Aetna patients demonstrated a 97% rate of HER2 testing, and showed that documentation was not related to age, tumor pathology, or sociodemographic factors.32 The contrasting rates of HER2 documentation between the Aetna study and this analysis underscore the regional reporting variation across Ontario LHINs. This variation provides an important caveat for researchers studying personalized medicine practice using a centralized, cancer registry–driven data source and provides support for the ongoing effort to adopt collaborative staging standards in Ontario.33

Incomplete HER2 test documentation in centrally held reports makes interpretation of these findings challenging, which in turn has implications for efforts to improve the quality of personalized medicine through research and monitoring. Recent calls for better evidence to evaluate personalized medicine practice have highlighted 2 challenges: (1) pricingbased reimbursement for diagnostic tests does not facilitate individual test identification in administrative data and (2) registries documenting testing and subsequent treatment decisions are lacking.34

We assessed the ability to document HER2 testing in Ontario across treatment settings and geographical locations, but found that HER2 status was not detailed in the OCR, and HER2 tests were not discernible from other diagnostics in billing data (despite being billed individually vs as a bundle). CCO’s repository of OCR pathology submissions provided a central source for pathology reports, but we identified several deficiencies in this source. Although submission of pathology reports to CCO to inform cancer diagnoses and staging in the OCR is mandatory, HER2 testing was not required for reporting at the time of this study. Moreover, HER2 tests tend to be reported on addendum pathology reports, which may not be submitted centrally unless the addendum alters diagnosis or staging for registry purposes. Differential use of electronic systems to manage and submit pathology reports at the laboratory level may also account for variability. These system factors may explain the high missingness of HER2 and other pathology factors in the cohort. Pathology reports as a source of HER2 information are also highly variable in format, detail, and structure.

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Issue: January 2013
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