Abstract P2-11-20: Challenging the current 1-10% cut-off for defining Estrogen Receptor Low Positive grade 2-3 Estrogen Receptor positive, Human Epidermal growth factor Receptor 2 negative early breast cancer
Authors: Roobroeck Bernard , Vanderstichele Adriaan , Floris Giuseppe , Desmedt Christine , Punie Kevin , Han Sileny , Smeets Ann , Janssen Hilde , Baten Adinda , Weltens Caroline , Nevelsteen Ines , Baert Thaïs , Wildiers Hans , Neven Patrick 
Published: March 2023

Abstract
Background: The 2020 ASCO-CAP guidelines (Allison KH, JCO 2020; 38: 1346–66) recommended estrogen receptor (ER) Low Positive as new reporting category for breast cancers with 1-10% of cells staining ER positive to acknowledge their distinct clinical behaviour compared to breast cancers with &gt;10% to 100% of tumor nuclei positive for ER. We evaluated the prognostic impact of low ER positivity with both 10% and 33% as cut-off. Patients and methods: A retrospective study was performed of consecutively treated patients in UZ Leuven between 2000-2017 with ER-positive/HER2-negative early, primary, unilateral and unifocal grade 2-3 invasive breast cancers. Patients treated with neo-adjuvant therapy were excluded. ER-positivity was defined as &gt;1% ER-staining on immunohistochemistry (IHC). Patients were allocated to ER-low or ER-high groups for both the 10% and 33% thresholds according to their ER-status on IHC as derived from the Allred PS or from the H-score. Descriptive analyses and Cox regression analyses were performed for both thresholds (≤ 10% vs. ≤ 33%) with α=0.05. Primary endpoints were overall survival (OS) and invasive disease-free survival (iDFS). Secondary endpoints were time to local (TTLR), locoregional (TTLRR) and distant metastatic relapse (TTM). Results: This study included 3629 patients (median age: 60.0 years; median follow-up: 12.3 years), with their tumors classified as low (39) versus high (3590) with 10% threshold and as low (92) versus high (3537) with 33% threshold. According to both cut-offs, grade 3 and PR negativity was more frequent in ER Low Positive breast cancer. These patients also received significantly more adjuvant chemotherapy and less adjuvant endocrine therapy. When looking at iDFS, OS, TTLR and TTLRR, both cut-offs generated groups with similar outcome. However, we observed a significant increased risk for distant metastatic relapse in ER Low Positive disease using the cut-off of 33% (univariate HR 2.0, 95%CI 1.3-3.2; p=0.009), which was not present for the cut-off of 10% (univariate HR 0.5, 95%CI 0.1-1.8; p=0.2). Nevertheless, when correcting this effect for age, grade, PR, tumor size, nodal status, adjuvant chemotherapy and endocrine therapy in multivariate analysis, ER Low Positive according to the cut-off of 33% did not remain significant to predict risk for metastatic relapse (HR 1.3, 95%CI: 0.8-2.3; p=0.3). Conclusion: In our series, patients with tumors expressing low ER, defined as 1-33% had a significantly higher univariate risk for metastatic relapse. ER Low Positive tumors are more frequently grade 3, which greatly determines the prognosis. ER Low Positivity did not remain independently significant after multivariate analysis. However, patients with tumors expressing low ER only constituted small fractions of the investigated population.
Citation Format: Bernard Roobroeck, Adriaan Vanderstichele, Giuseppe Floris, Christine Desmedt, Kevin Punie, Sileny Han, Ann Smeets, Hilde Janssen, Adinda Baten, Caroline Weltens, Ines Nevelsteen, Thaïs Baert, Hans Wildiers, Patrick Neven. Challenging the current 1-10% cut-off for defining Estrogen Receptor Low Positive grade 2-3 Estrogen Receptor positive, Human Epidermal growth factor Receptor 2 negative early breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-11-20.