Abstract P2-12-03: Phenotype shifting in early breast cancer with and without primary systemic treatment: A retrospective cohort analysis correlating core needle biopsies and excisional biopsies in 1250 consecutive real-world cases
Authors: Argyriadis Athanasios , Bange Michael , Mehta Keyur , Loibl Sibylle , Khodaverdi Silvia , Braun Susanne , Denkert Carsten , Jackisch Christian 
Published: March 2022

Introduction: Breast cancer (BC) is a heterogenous disease, composed of various subclones with different response to treatment strategies, known as clonal sensitivity. PST might modulate the biology of BC cells and thus, the molecular subtype. In our single-center, retrospective cohort analysis we evaluated the concordance of the molecular subtype using ER, PR, HER2 status and Ki67 based on the core needle biopsies (CNB) and the excisional biopsies (EB) in primary, early breast cancer (eBC) with and without primary systemic treatment (PST). Finally, we analyzed the subtype shifting in residual tumors after PST.Methods: From January 1st, 2007 to December 31st, 2016 we identified a total of 1250 consecutive eBCs with corresponding samples from the CNB and the EB were analyzed. Upfront surgery after CNB was performed during the observational period in 1002 eBCs, allowing us to compare the histopathological findings of the CNB and the EB in pairs (cohort C1). PST followed by surgery was performed in 248 eBCs. A pathological complete response (pCR) was achieved in 60 cases. One patient with a clinical complete response (cCR) after PST, refused surgery and was excluded from the analysis. A non-pCR as best response was detected after the completion of PST in 187 eBCs, allowing us to compare the histopathological findings of the CNB and the EB in pairs (cohort C2). The analysis was performed separately in C1 and C2 and the final results were compared.Results: In C1 subtype shifting between CNB and EB in C1 was 18.2% for luminal A, 33.0% for luminal B HER2-, 27.8% for luminal B HER2+, 19.3% for HER2 enriched and 10.1% for basal like tumors. In C2, it was 31.5% for luminal A, 49.1% for luminal B HER2-, 39.0% for luminal B HER2+, 23.1% for HER2 enriched and 9.0% for basal like tumors. Regarding ER, PR, HER2 status and Ki67 we identified between CNB and EB in C1 the following discrepancies: 2.0%, 10.0%, 6.0%, 20.3% and in C2 the following treatment related changes: 8.3%, 27.1%, 11.4%, 52.1%. The number of CNBs had no influence on the changes above. Significant variations in subtype shifting based on PST were identified in C2 compared to C1.Conclusion: In C1 we demonstrated a high concordance of the prognostic factors, identified by one experienced pathologist, allowing us to validate the differences induced by PST. In C2 we demonstrated a significant phenotype shifting, which was dominated by the luminal B subtype. Besides fixational and observational issues, intratumoral heterogeneity of BC and the subsequent clonal sensitivity may explain our results. Present experimental data are suggesting that this treatment related changes might be transient in nature. Prospective data will clarify, if this observation might be therapy relevant, or if the subclones dominating the residual tumor in non-pCR require new post-neoadjuvant treatment approaches.

Molecular Subtypes in CNB and EB with and without PSTLuminal ALuminal B HER2-Luminal B HER2+HER2 enrichedBasal likeC1CNB59.1%24.8%6.9%3.4%5.8%EB56.0%26.0%8.7%3.5%5.8%C2CNB22.6%34.2%23.8%7.2%12.2%EB50.4%29.2%17.4%6.7%16.3%

Citation Format: Athanasios Argyriadis, Michael Bange, Keyur Mehta, Sibylle Loibl, Silvia Khodaverdi, Susanne Braun, Carsten Denkert, Christian Jackisch. Phenotype shifting in early breast cancer with and without primary systemic treatment: A retrospective cohort analysis correlating core needle biopsies and excisional biopsies in 1250 consecutive real-world cases [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-12-03.