Concordance and clinical impact of ER, PR, HER2 expression by local and central immunohistochemistry versus RT-PCR in HR+/HER2- early breast cancer (EBC): Results from the ADAPT trial
| العنوان: | Concordance and clinical impact of ER, PR, HER2 expression by local and central immunohistochemistry versus RT-PCR in HR+/HER2- early breast cancer (EBC): Results from the ADAPT trial |
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| المؤلفون: | Oleg Gluz, Matthias Christgen, Sherko Kuemmel, Christine zu Eulenburg, Michael Braun, Bahriye Aktas, Kerstin Luedtke-Heckenkamp, Helmut Forstbauer, Eva-Maria Grischke, Claudia Schumacher, Katja Krauss, Marc Thill, Mathias Warm, Monika Karla Graeser, Rachel Wuerstlein, Ronald E. Kates, Frederick L. Baehner, Ulrike Nitz, Hans Heinrich Kreipe, Nadia Harbeck |
| المصدر: | Journal of Clinical Oncology. 40:536-536 |
| بيانات النشر: | American Society of Clinical Oncology (ASCO), 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Cancer Research, Oncology |
| الوصف: | 536 Background: We evaluated concordance of ER, PR and HER2 status between local, central, and RT-PCR/mRNA assessments and its clinical impact in the ADAPT trial collective in HR+ HER2- EBC (NCT01779206). Particularly, validity of borderline ER-positivity (expression level 1-10%) has great clinical relevance as treatment concepts between luminal-like and triple negative (TNBC) EBC differ substantially. Methods: Patients (pts) with clinically high-risk HR+/HER2- EBC (ER and/or PR >1%) were initially treated by 3 (+/-1) weeks of endocrine therapy (ET) before surgery or sequential core biopsy (CB) and then allocated to an ET-alone or chemotherapy (ET) trial, depending on risk and endocrine response. OncotypeDX (incl. RT-PCR for ER, PR, HER2) and central IHC for ER, PR, HER2 were performed on the initial 1.CB. ER-low cohort was defined as 1-10% expression by local OR central lab (ASCO-CAP). Cox models were used to estimate hazard ratios. Results: In ADAPT, 5149 pts from 81 centers in Germany with locally ER and/or PR positive (known quantitative levels) EBC were screened 2012-2018. Median follow-up was 59 months. For ER (positive vs. negative), overall concordance measured as agreement (κ) was high between all three assessments: Local vs. central IHC: 99.3% (κ = 0.45), RT-PCR vs. central IHC: 99% (κ = 0.48). Concordance was lower for PR: RT-PCR vs. central IHC: 90.5% (κ = 0.58), local vs. central IHC: 93.1% (κ = 0.56). 3% were centrally found as HER2+ in 1.CB (73% of them were negative by RT-PCR) and/or 2. Sample. Regarding HER2-low status (1+ or 2+ but ISH negative), concordance between local and central IHC was only 53.8% (κ = 0.09). Of all pts, only 2% (n=109; n=85 with both measurements available) had low ER expression (1-10%) by either local or central pathology. Only 9 of them were concordantly identified as ER-low (11%); 8/58 (14%) ER-low by local lab had TNBC by central lab. 17/47 ER-low cases (36.2%) with known post-endocrine Ki67post had Ki67post 10%. 41.8% of ER-low cases had RS10%. All cases with ER 25. We observed worse iDFS (HR 1.91, p=0.034) in the ER-low group vs. ER>10%. Conclusions: Although we have confirmed high agreement between local and central IHC and RT-PCR for ER, PR, HER2 assessment in locally HR+/HER2- EBC, there are still a few clinically relevant discordances. Regarding HER2-low status, standardization and quality assurance are needed if this becomes clinically relevant. Treatment of the heterogeneous ER-low group as TNBC appears reasonable only if “ER-low” is confirmed by a second assessment and in cases with Ki-67>40%. Preoperative ET response assessment may be helpful if an endocrine-based therapy concept is intended. Clinical trial information: NCT01779206. |
| تدمد: | 1527-7755 0732-183X 0177-9206 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::3633f05fe6ec297f48111b743e85587f https://doi.org/10.1200/jco.2022.40.16_suppl.536 |
| رقم الأكسشن: | edsair.doi...........3633f05fe6ec297f48111b743e85587f |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15277755 0732183X 01779206 |
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