Abstract P6-08-53: Her2 FISH amplification in ER/PR/Her2 IHC negative breast cancer
Authors: Sunati Sahoo, Helena Hwang
Journal: Cancer Research (2015)

Abstract Background: Triple negative (ER negative, PR negative, Her2 negative) breast cancer is an aggressive cancer that is not likely to respond to endocrine or anti-Her2 therapy. While Her2 positivity is a poor prognostic factor, patients with Her2 positive tumors are eligible for anti-Her2 therapy. Her2 positivity is based on either immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH) result. Her2 IHC scores of 0+ and 1+ are negative, 2+ is equivocal, and 3+ is positive. The Her2 gene is amplified when the Her2/CEP17 ratio is ≥2.0. While most tumors will show IHC/FISH concordance, some tumors may show discordant findings between IHC staining and FISH. Previous studies have shown benefit from anti-Her2 therapy in tumors with discordant IHC/FISH results. The purpose of this study was to determine the frequency of Her2 amplification in triple IHC negative breast cancer to determine whether routine Her2 FISH testing is necessary in this subset of patients. Methods: After Institutional Review Board approval, the pathology databases were searched for cases of triple IHC negative breast cancer from 2003-August 2013. All cases of triple IHC negative with corresponding Her2 FISH testing were included in this study. The results of Her2 FISH were correlated with Her2 IHC. The clinical history and IHC slides for all discordant Her2 cases were reviewed when available. Results: A total of 659 triple IHC negative breast cancer cases from 516 patients were found. The patients’ age at diagnosis ranged from 26-92. The cases were classified using the ratio of Her2/CEP17 per the 2013ASCO/CAP guidelines: non-amplified &amp;lt; 2.0, amplified ≥ 2.0. As the copy number for Her2 was not always available, the 2013 ASCO/CAP criterion for amplification based on the copy number was not used in reclassifying the cases. Based on the ratio, 20 tumors were amplified, 631 tumors were not amplified, and 8 tumors had insufficient tissue for Her2 FISH testing. The Her2/CEP17 ratio for amplified cases ranged from 2.0 to 11.1 and for non-amplified cases from 0.5 to 1.9. Of these 20 patients, 10 received some trastuzumab treatment, 6 did not receive any trastuzumab, and in 4 patients, there was no additional information available regarding treatment with trastuzumab. Of the 10 who received trastuzumab treatment, 2 died of disease (DOD), 26 months and 45 months after their diagnosis. The overall survival of the other patients in this group was 23-106 months. Of the 6 who did not receive trastuzumab, one DOD after 76 months. The other 5 patients have overall survival ranging from 15-93 months. Of the patients with unknown Her2 targeted therapy status, one is deceased, the status of 2 is unknown, and one patient is alive at 110 months. Discussion: Our study showed 3% of triple IHC negative breast cancers to be Her2 FISH amplified. Of the 20 tumors, 19 showed Her2/CEP17 between 2.0 to 4.2 with one case showing Her2/CEP17 of 11.1. Firm conclusions on the efficacy of trastuzumab treatment in this small subset of patients with Her2 amplification but no protein overexpression cannot be drawn. However, the overall survival of those treated and not treated is similar. Based on the small number of cases with Her2 IHC/FISH discordance, a compelling case for routine testing of all Her2 IHC negative tumors cannot be made. Citation Format: Sunati Sahoo, Helena Hwang. Her2 FISH amplification in ER/PR/Her2 IHC negative breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P6-08-53.