A joint letter to the editor¹ to the Journal of Clinical Oncology provides an important reminder of the intent of the ASCO/College of American Pathologists (CAP) guideline panel on human epidermal growth factor receptor 2 (HER2)² and a reconciliation of some pathology technical aspects. The topic of establishing equivocal categories for prognostic and predictive markers in breast cancer has generated frequent discussion. The letter by Elizabeth Hammond, MD, Daniel F. Hayes, MD, and Antonio Wolff, MD, Co-chairs of the ASCO/CAP guideline panels on HER2 testing and immunohistochemistry (IHC) testing of estrogen receptor/progesterone receptor testing, states:

In particular, the equivocal categories for HER2 were meant to trigger HER2 reflex testing using another validated assay if the first test is equivocal (IHC if an equivocal fluorescent in situ hybridization [FISH] test or FISH if an equivocal IHC test). The Panel felt this approach would provide clinicians and their patients with additional information for clinical decision-making. Figure 2 of the January 2007 HER2 Guideline clearly stated that patients with a HER2/CEP17 (chromosome enumeration probe 17) FISH amplification ratio ≥ 2.0 were eligible for the trastuzumab adjuvant trials, including those with a ratio between 2.0 and 2.2. In a subsequent letter³ to Journal of Clinical Oncology in September 2007, we then revised Figure 1 of the guideline document to state that patients with a HER2 2+ equivocal IHC test who had tumors with uniform intense membrane staining in more than 10% and less than 30% of cells were also eligible for the trastuzumab trials. Most critical to this discussion, we then stated that “Available data from the adjuvant trials at present are insufficient to reliably exclude these patients from therapy with trastuzumab….” The Panel did not recommend withholding anti-HER2 treatment in those patients with an equivocal HER2 test (or tests) whose results fell within ranges that would have allowed them to be treated in the first generation of adjuvant HER2-targeted trials.

The full letter¹ to JCO can be accessed at http://jco.ascopubs.org/content/early/2011/04/18/JCO.2011.35.2245.full.pdf+html. ■

References

1. Hammond ME, Hayes DF, Wolff AC, et al: Clinical notice for American Society of Clinical Oncology–College of American Pathologists guideline recommendations on ER/PgR and HER2 testing in breast cancer. J Clin Oncol. April 18, 2011 (early release online).

2. Wolff AC, Hammond ME, Schwartz JN, et al: American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. J Clin Oncol 25:118-145, 2007.

3. Wolff AC, Hammond ME, Schwartz JN, et al: Correspondence: In reply. J Clin Oncol 25:4021-4023, 2007.