Rate of reclassification of HER2-equivocal breast cancer cases to HER2-negative per the 2018 ASCO/CAP guidelines and response of HER2-equivocal cases to anti-HER2 therapy.

James Crespo,Hui Chen,Melissa K Robinson,Bora Lim,Hongxia Sun,Aysegul A Sahin,Guilin Tang,Jimin Wu,Qing-Qing Ding,Paul J Van Diest

doi:10.1371/journal.pone.0241775

Abstract

The 2018 American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guideline on HER2 testing in breast cancer permits reclassification of cases with HER2-equivocal results by FISH. The impact of such reclassification is unclear. We sought to determine the proportion of HER2-equivocal cases that are reclassified as HER2-negative and the impact of anti-HER2 therapy on survival in HER2-equivocal cases. We reviewed medical records of breast cancer patients who had HER2 testing by fluorescence in stitu hybridization (FISH) and immunohistochemistry (IHC) performed or verified at The University of Texas MD Anderson Cancer Center during April 2014 through March 2018 and had equivocal results according to the 2013 ASCO/CAP guideline. The population was divided into 2 cohorts according to whether the biopsy specimen analyzed came from primary or from recurrent or metastatic disease. HER2 status was reclassified according to the 2018 ASCO/CAP guideline. Overall survival (OS) and event-free survival (EFS) were calculated using the Kaplan-Meier method, and the relationship between anti-HER2 therapy and clinical outcomes was assessed. We identified 139 cases with HER2-equivocal results according to the 2013 ASCO/CAP guideline: 90 cases of primary disease and 49 cases of recurrent/metastatic disease. Per the 2018 ASCO/CAP guideline, these cases were classified as follows: overall, HER2-negative 112 cases (80%), HER2-positive 1 (1%), and unknown 26 (19%); primary cohort, HER2-negative 85 (94%), HER2-positive 1 (1%), unknown 4 (4%); and recurrent/metastatic, HER2-negative 27 (55%) and unknown 22 (45%). Five patients in the primary-disease cohort and 1 patient in the recurrent/metastatic-disease cohort received anti-HER2 therapy. There was no significant association between anti-HER2 therapy and OS or EFS in either cohort (primary disease: OS, p = 0.67; EFS, p = 0.49; recurrent/metastatic-disease, OS, p = 0.61; EFS, p = 0.78. The majority of HER2-equivocal breast cancer cases were reclassified as HER2-negative per the 2018 ASCO/CAP guideline. No association between anti-HER2 therapy and OS or EFS was observed. HER2-equivocal cases seem to have clinical behavior similar to that of HER2-negative breast cancers.

Highlights

Breast cancer is the most common cancer diagnosed among women worldwide and remains the principal cause of cancer death among women worldwide [1]
We reviewed medical records of breast cancer patients who had human epidermal growth factor receptor 2 (HER2) testing by fluorescence in stitu hybridization (FISH) and immunohistochemistry (IHC) performed or verified at The University of Texas MD Anderson Cancer Center during April 2014 through March 2018 and had equivocal results according to the 2013 ASCO/CAP guideline
We identified 139 cases with HER2-equivocal results according to the 2013 ASCO/CAP guideline: 90 cases of primary disease and 49 cases of recurrent/metastatic disease

Summary

Introduction

Breast cancer is the most common cancer diagnosed among women worldwide and remains the principal cause of cancer death among women worldwide [1]. Implementation of the 2013 American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guideline on HER2 testing in breast cancer, compared with the previous guideline from 2007, resulted in increases in the proportion of HER2-positive breast cancers and the proportion of cases with HER2-equivocal results [11,12,13,14]. The 2018 ASCO/CAP guideline attempted to decrease the number of cases with equivocal results by creating 5 groups based on both FISH and IHC results [15]. The 2018 ASCO/CAP guideline permits cases in group 4 to be further classified as HER2-positive or HER2-negative based on IHC staining for HER2 done using sections from the same tissue sample used for FISH. If FISH shows a HER2/CEP17 ratio of 4, the diagnosis is HER2-positive; otherwise the diagnosis is HER2-negative

Methods

Results

Conclusion