Re: predictability of adjuvant trastuzumab benefit in N9831 patients using the ASCO/CAP HER2-positivity criteria.

In a retrospective analysis of the adjuvant trastuzumab trial N9831 recently published in the Journal, Perez et al . ( 1 ) compared the frequency of HER2-positive status as was determined by the US Food and Drug Administration (FDA) criteria for eligibility for the trial with post hoc criteria proposed by the 2007 American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) HER2 Testing Panel ( 2 ). They concluded that the FDA, rather than ASCO/CAP criteria should be used to determine the eligibility of breast cancer patients for trastuzumab adjuvant therapy. Indeed, this recommendation is not dissimilar from the original recommendations of the ASCO/ CAP HER2 Testing Panel ( 3 , 4 ). The Panel recommended that “equivocal” categories be established for HER2 that were meant to trigger HER2 reflex testing using another appropriately validated assay platform such as fluorescent in situ hybridization (FISH) if immunohistochemical (IHC) staining for HER2 was equivocal or with IHC if FISH results were equivocal. In this regard, the ASCO/CAP Panel recommended that the percentage of cells with strong uniform membrane staining by IHC required to deem a case 3+ be increased from the 10% used in the FDA eligibility requirements to 30% and that 11% – 29% should be considered equivocal and trigger confirmatory FISH testing. The Panel also recommended routine proficiency testing, which has since been widely adopted by the pathology community as shown by the uptake since the year 2007 in the numbers of labs in the United States and elsewhere participating in predictive marker proficiency testing as part of the College of American Pathologists Laboratory Improvement Program ( Figure 1 ) ( 5 ). Overall, the Panel felt that this strategy would provide clinicians and patients with additional confidence as eligibility for adjuvant trastuzumab was determined ( 4 ). Figure 1 . The number of laboratories participating in predictive marker profi ciency testing for HER2 and estrogen receptor (ER) as part of the College of American Pathologists Laboratory Improvement Program ( http :// www . cap . org / apps / cap . portal ? _nfpb = true & _pageLabel = accreditation ). The number of laboratories that participated each year are shown. The years during which the HER2 and Hormone Receptor Testing guidelines were published by ASCO/CAP are indicated by the arrows . The numbers of participating laboratories are shown both graphically and in table form. FISH = fl uorescent in situ hybridization; IHC = immunohistochemical; PR = progesterone receptor.