Prognosis and categorization of HER2 fluorescent in-situ hybridization (FISH) results in patients with invasive breast cancer who received HER2 targeted agents: Analysis of 226 patients

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Conference Proceeding

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Modern Pathology


Background: In management of invasive breast cancers (IBC), status of HER2 (ERBB2) gene serves as a strong prognostic predictor & predictive marker of response to HER2 Targeted Agents (HTA). There is significant heterogeneity in response to these agents in HER2- positive cases. Our aim was to determine the distribution of the status of HER2 by FISH in IBC along with its predictive implications. Design: IBC cases that were tested for HER2FISH & received HTA from 2006-2017 were identified. HER2FISH was interpreted using the ASCO/CAP guidelines at the time of reporting. Cases were grouped as follows: 1) Monosomy (ratio ≥2.0, mean HER2/cell<4.0) 2) Co- Amplified (ratio<2.0, mean HER2/cell ≥6.0) 3) Low amplified (ratio ≥2.0, mean HER2/cell 4.0-5.9) 4) Amplified (ratio ≥2.0-2.99, mean HER2/cell >6) 5) Excessive Amplification (ratio ≥3.0) 6) 2013 Equivocal (ratio<2.0, mean HER2/cell 4.0-5.9) 7) Negative. Outcomes studied were recurrence, metastasis, second breast primary, disease specific survival (DSS) & overall survival (OS). Results: There were 226 cases, with median age 65 (range 26-98), 58% Caucasians, 24% African Americans, 1.5% others & 16.5% unknown. The median HER2FISH ratio was 2.47 (1.18-21) & HER2 signal/cell 5.71 (2.09-21). Table 1 shows categoric distribution of cases. 60/226-27% patients received neoadjuvant chemotherapy, 139/226-62% hormonal therapy, 187/226-83% adjuvant & 146/226-65% radiotherapy. The median follow up was 207 weeks (4.3-708). Overall, 165/226-73% patients were alive without disease, 17/226-7% alive with disease, 33/226-15% died of IBC & 11/226-5% died due to other causes. 31/226-14% patients developed metastasis, 7/226-3% local recurrence & 4/226-2% second breast primary. The category of HER2FISH status was significantly associated with OS (p<0.05-Figure1), higher HER2 amplification was associated with fewer deaths, possibly reflecting a better response to HTA. Her2FISH status also statistically significantly relates to metastasis (p=0.04-Figure 2) & second primary (p<0.05) but not with recurrence (p=0.09) or DSS (p=0.5) in our cohort. (Table presented) Conclusions: The current HER2FISH interpretation does not stratify as high or low amplification based on FISH results. In our study, we demonstrate that high HER2 amplification is significantly associated with longer OS; these patients seem to benefit more from HTA. We recommend reporting these categories when assessing HER2FISH in IBC. Larger, prospective longitudinal studies are needed to validate our findings.





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