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[136] Impact of the New American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) Guidelines on the Determination of Breast Cancer HER2 Status

HL Gilmore, LC Collins, JL Connolly, SJ Schnitt. Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA

Background: In January 2007, ASCO/CAP issued new guidelines for HER2 testing of breast cancers (J Clin Oncol 2007;25:118-145). Among the changes in these guidelines, a breast cancer must now show uniform, intense membrane staining in >30% of invasive tumor cells (rather than >10%) to be considered HER2 positive (3+) by immunohistochemistry (IHC). The stated goal of this change is to decrease the incidence of false positive 3+. However, its impact on the assignment of HER2 status by IHC and on correlation between IHC and fluorescence in situ hybridization (FISH) results has not been previously evaluated.
Design: Between January and August 2007, both IHC (Dako rabbit polyclonal antibody A085) and FISH (PathVysion, Vysis) were performed on 215 consecutive invasive breast cancers accessioned at our institution. IHC results were scored as 0-1+ (negative), 2+ (equivocal) and 3+ (positive) using both the original HercepTest criteria and the new ASCO/CAP guidelines. Results of IHC were compared with those obtained by FISH. Based on the new guidelines, FISH results were scored as not amplified, equivocal or amplified when the HER2/CEP17 ratio was <1.8, 1.8-2.2, or >2.2, respectively.
Results: Using the original HercepTest scoring criteria with a 10% threshold for 3+ positivity, 153 cases (71%) were IHC 0-1+, 35 (16%) were 2+, and 27 (12%) were 3+. Correlation between IHC and FISH results is shown in the Table. Ninety-five percent of cases that were IHC negative also lacked gene amplification by FISH. Conversely, 93% of IHC 3+ cases showed HER2 gene amplification. Of note, all 27 cases scored as 3+ by IHC using the >10% cut-off remained 3+ using the new cut-off of >30%. Thus, the concordance between IHC 3+ cases and FISH results was unchanged when the new ASCO/CAP guidelines for IHC scoring were employed.
Conclusions: The results of this study suggest that the new ASCO/CAP guidelines for HER2 scoring are unlikely to have a substantial impact on the proportion of cases categorized as HER2 positive (3+) by IHC or, in turn, on the level of concordance between IHC and FISH among IHC-positive cases.

Comparison of HER2 by IHC and FISH

	FISH Not Amplified (HER2/CEP17 <1.8)	FISH Equivocal (HER2/CEP17 1.8-2.2)	FISH Amplified (HER2/CEP17 >2.2)
IHC 0-1+ (negative)	145	2	6
IHC 2+ (equivocal)	22	4	9
IHC 3+ (positive)	2	0	25

Category: Breast

Monday, March 3, 2008

Poster # 27, Monday Morning