Abstract P3-08-04: Impact of ER-positivity on time and pattern of relapse in early-stage breast cancer patients
Authors: LeVasseur Nathalie , Willemsma Kaylie-Anne , Lohrisch Caroline , Gondara Lovedeep , Speers Caroline , Simmons Christine , Nichol Alan , Gelmon Karen 
Published: March 2020

Abstract
Background: While it is well recognized that ER positivity is predictive of response to endocrine therapy for patients with early-stage breast cancer (EBC), the method to assess ER level has evolved over time. The applicability of early trial data to clinical practice using contemporary methods of assessment is unclear. Clinical trials of hormone therapy, which inform clinical practice, do not correlate the ER level of positivity to the magnitude of benefit. Given that most newly diagnosed EBCs are ER positive, it is important to determine if the level of ER positivity as determined by current IHC methodology and scoring systems affect the frequency, time and pattern of relapse in patients with low, moderate or high ER positivity. Methods: The BC Cancer Breast Cancer Outcomes Unit (BCOU) database was utilized to identify patients with EBC referred to BC Cancer from 2005-2014. Baseline clinical, pathological and treatment criteria were compiled. Patients were divided into 3 groups, defined as “ER low” (Allred 3-4 OR IHC 1), “ER moderate” (Allred 5-6 OR IHC 2) or “ER high” (Allred 7-8 OR IHC 3). Event-free survival (EFS) was compared across the 3 groups using Kaplan-Meier survival curves in univariate and multivariate models. Key secondary endpoints included breast-cancer specific survival (BCSS) and overall survival (OS). Additional secondary endpoints included local-regional free survival (LRFS) and distant-disease-free survival (DDFS) and sites of relapse. Results: A total of 14,260 patients met the inclusion criteria consisting of 492 (3.5%) ER low, 1,088 (7.7%) ER moderate and 12,613 (88.9%) ER high patients. Median age was 55yrs (24-91) in the ER low, 53yrs (23-92) in the ER moderate and 61yrs (22-99) in the ER high groups (p&lt;0.001). A total of 66.1%, 69.6% and 76.8% had stage I or IIa cancers in the ER low, moderate and high groups, respectively (p&lt;0.001). Overall, grade 3 was present in 78.0%, 42.8% and 23.7% of patients in the ER low, moderate and high groups, respectively (p&lt;0.001). HER2 positivity was present in 34.1% of the ER low, 24.1% of the ER moderate and 8.5% of the ER high groups (p&lt;0.001). Systemic treatment received consisted of chemotherapy with subsequent hormone therapy in 76.4% of the ER low, 61.1% of the ER moderate and 34.4% of the ER high patients, whereas the rest received hormone therapy alone. Median follow-up was 7.4 yrs. 5-year EFS was 80% (95% CI 76, 84) in the ER low group, 87% (85, 89) in the ER moderate group and 89% in the ER high group (88, 90) in univariate analysis; p=0.004. This remained statistically significant in multivariate analysis when comparing the ER high to the ER low and moderate groups; p=0.01. 10-year EFS was 75% (70, 80) in the ER low, 77% (74, 79) in the ER moderate and 77% (76, 78) in the ER high groups; p=0.004. 5-year BCSS was 89% (86, 92), 94% (93, 95) and 97% (96, 98) in the ER low, moderate and high groups, respectively; p&lt;0.0001. 5-year OS was 85% (82, 88), 91% (89, 93) and 93% (92, 94) for the ER low, moderate and high groups, respectively; p=0.03. Local recurrences were more frequent in ER low patients, as opposed to the ER moderate or high groups; p&lt;0.001. Distant relapses were also more frequent in the ER low group when compared to the ER moderate and high groups; p&lt;0.001. Distant sites of recurrence were also significantly different amongst groups (p=0.091), although absolute differences were small. Conclusions: The level of ER positivity was significantly associated with all survival parameters in a real-world setting. This large series highlights the importance of the ER level as a predictive and prognostic marker for patients with EBC. Patterns of relapse including the timing of recurrence will be also described. Research on the optimal treatment and duration of therapy for patients with low to moderate ER positivity is needed to improve outcomes and further define the impact of endocrine therapy for the ER low group.
Citation Format: Nathalie LeVasseur, Kaylie-Anne Willemsma, Caroline Lohrisch, Lovedeep Gondara, Caroline Speers, Christine Simmons, Alan Nichol, Karen Gelmon. Impact of ER-positivity on time and pattern of relapse in early-stage breast cancer patients [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-08-04.