Equivocal HER2 FISH Results on Breast Core Biopsy with Ratio <2.0: Repeat HER2 Testing on Excision Specimens Impacts Patient Management
Chad Livasy, Benjamin Calhoun, Steven Limentani. Levine Cancer Institute, Charlotte, NC
Background: In the first generation HER2 adjuvant clinical trials, a ratio of 2.0 was used as the cutpoint to determine eligibility for trastuzumab therapy for patients whose tumors were tested by FISH. The ASCO/CAP guidelines subsequently defined cases showing a ratio of 1.8-2.2 as equivocally amplified. HER2 equivocal tumors present a challenge to oncologists who must decide whether or not to give HER2 targeted therapy. There are no clear evidence-based guidelines for how to resolve the HER2 status for equivocally amplified tumors. The identification of HER2 genetic heterogeneity within tumors raises the possibility that sample size may be an important factor in accurately determining HER2 status, particularly for cases near the cutpoint. This study evaluates the potential clinical impact of HER2 retesting on excision specimens for patients with HER2 FISH equivocal results showing a ratio <2.0 on core biopsy, who would otherwise not be eligible for HER2 targeted therapy.
Design: A total of 35 breast core biopsy specimens were identified from our database showing invasive mammary carcinoma and an equivocally amplified HER2 status (ratio <2.0) who had retesting of HER2 status by FISH on the subsequent excision specimen. The HER2 ratios from the core biopsy and excision specimen were compared. Changes in HER2 status between the core biopsy and excision specimen were noted using ASCO/CAP criteria.
Results: A definitive change in the classification of the HER2 status was observed in 24 (68%) cases. Twenty cases (57%) reclassified as negative, 4 cases (11%) reclassified as positive, and 11 cases (31%) remained equivocal. Three of the patients with HER2 equivocal results on the excision specimen demonstrated a ratio >2.0. Using a ratio of 2.0 as the cutpoint for determining eligibility for HER2 targeted therapy, a total of 7 (20%) of patients became eligible for trastuzumab therapy. The four patients who showed a definitive reclassification to HER2-positive status showed ratios of 4.0, 3.0, 2.5 and 2.4.
Conclusions: For patients with equivocally HER2 amplified results on core biopsy showing a ratio <2.0, repeat HER2 FISH testing on a larger volume of invasive carcinoma from excision specimens results in definitive reclassification of HER2 status for a significant number of patients. Approximately 1/5 of patients became eligible for HER2 targeted therapy based on results from the excision specimen. These results support the ASCO/CAP recommendations for further testing of cases with HER2 equivocal results.
Tuesday, March 5, 2013 1:00 PM
Poster Session IV # 36, Tuesday Afternoon