Abstract P2-09-25: Clinical and pathologic characteristics of breast cancers determined to be HER2-positive by fluorescence in-situ hybridization (FISH) using alternative chromosome 17 probes
Authors: Desai NV , Torous V , Cruz C , Schnitt SJ , Tung N 
Published: February 2018

Abstract
Background:
Based on updated 2013 ASCO/CAP guideline for HER2 testing, cases with a HER2/CEP17 ratio &lt; 2.0 but with an average HER2 copy number &gt; 4.0 and &lt;6.0 signals/cell are considered equivocal. In such cases, HER2 testing using alternative chromosome 17 probes was proposed as one way to resolve the equivocal FISH results. Using the alternative probe method increases the number of cancers categorized as HER2 positive but brings to question if these cancers truly represent HER2 amplified breast cancers and derive the same benefit from anti-HER2 therapies.
Methods:
Since 2013, all breast cancers at our institution that were HER2 equivocal by traditional FISH but classified as HER2 positive using the alternative probe method were assessed for clinical and pathologic features including histologic type and grade, TNM stage, HER2: alternative probe ratio, treatment, and clinical outcome.
Results:
We identified 24 invasive breast cancers considered HER2 positive by the alternative probe method: 23 (96%) were estrogen receptor-positive (ER+) and 20 (83%) were progesterone receptor- positive. Histologically, only 2 were invasive lobular carcinomas; all others were ductal or had ductal and lobular features. Most cancers (63%) had low or intermediate histologic grade: Grade 1 (n=3); Grade 2 (n=12); Grade 3 (n=9). Clinical information was available for 18 patients: 2 had metastatic disease, 1 had a local recurrence after mastectomy and 15 patients had early stage disease; 9 with node negative disease and 6 with nodal involvement. HER2 IHC was equivocal (2+) in 16 (66.7%) cases, positive (3+) in 4 (16.7%) cases, and negative (0 or 1+) in 4 (16.7%) cases. The average HER2 copy number was 4.77, the average HER22:p53 ratio was 2.61. Repeat HER2 testing on a 2nd tumor sample was performed in 8 cases: HER2-positivity was confirmed in only 2 (25%) cases and by the alternative probe only. Treatment information was available for 17 patients: 1 had T1aN0M0 lesion and did not get chemotherapy, 16 received chemotherapy and 13 received trastuzumab-based chemotherapy. Eleven patients with early stage disease received chemotherapy and trastuzumab. Of these patients, 10/11 were ER+, 7/11 were node negative and 5/11 had grade 2 tumors, yet only one tumor was assessed by oncotype recurrence score ( RS = 29). Three patients received chemotherapy and trastuzumab in the neoadjuvant setting: 1 had a complete pathologic response, 1 a partial response, and 1 has not yet gone to surgery. One additional patient received neoadjuvant chemo alone and achieved a partial response.
Conclusions:
Breast cancers considered HER2+ by the alternative probe method but not by traditional FISH are almost always ER-positive and most have low or intermediate histologic grade. Repeat HER2 testing on a subsequent tumor sample did not confirm HER2-positivity in 75% of cases. Almost all patients with early stage disease received chemotherapy and trastuzumab based on the alternative probe results without molecular assessment to predict chemotherapy response. Intrinsic molecular subtyping using PAM50 analysis on these cancers is underway to determine how many are HER2-enriched by molecular assessment.
Citation Format: Desai NV, Torous V, Cruz C, Schnitt SJ, Tung N. Clinical and pathologic characteristics of breast cancers determined to be HER2-positive by fluorescence in-situ hybridization (FISH) using alternative chromosome 17 probes [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P2-09-25.