Abstract P3-08-29: Landscape of HER2-low metastatic breast cancer (MBC): Results from the AGMT-MBC-Registry
Authors: Gampenrieder Simon Peter , Rinnerthaler Gabriel , Petzer Andreas , Tinchon Christoph , Fuchs David , Balic Marija , Heibl Sonja , Rumpold Holger , Egle Daniel , Zabernigg August Felix , Singer Christian Fridolin , Andel Johannes , Hubalek Michael , Knauer Michael , Greil Richard 
Published: March 2020

Background: About 50% of all primary breast cancers show a low-level expression of HER2 (HER2-low), defined as immunohistochemically 1+ or 2+ and lack of HER2 gene amplification measured by in-situ hybridization. This low HER2 expression is a promising new target for antibody-drug conjugates (ADCs) currently under development. Until now, little is known about the frequency and the prognostic value of low HER2-expression in metastatic breast cancer (MBC). Patients and methods: The MBC-Registry of the Austrian Study Group of Medical Tumor Therapy (AGMT) is a multicenter nationwide ongoing retrospective and prospective registry for MBC patients in Austria. Unadjusted, univariate survival probabilities of PFS and OS were calculated by the Kaplan-Meier method and compared by the log-rank test, multivariate hazard ratios (HR) were estimated by Cox regression models. In this analysis patients with known HER2 status and available survival data were included. Results: As of 31/01/2019, 1,253 patients were included in the AGMT-MBC-Registry. Out of 1,079 evaluable patients, 262 (24.3%) were HER2-positive, 372 (34.5%) were HER2-low and 445 (41.2%) were completely HER2-negative (HER2-0). The distribution of hormone receptor (HR) expression is shown in Table 1. Median OS and median first-line PFS for these three subgroups in dependency of HR expression is presented in Table 2. Neither in univariate (p=0.821) nor in multivariate analysis including HR status, disease-free survival (DFS), age and visceral disease (p=0.590, HR 1.06), low HER2 expression had a significant impact on prognosis compared to completely HER2-negative disease. Overall 13/372 (3.5%) of the HER2-low and 11/445 (2.5%) of the HER2-0 patients received anti-HER2 treatment. In the HER2+ cohort 200/262 (76.3%) were treated with trastuzumab, 106 (40.5%) with pertuzumab and 49 (18.7%) with T-DM1. In the HR+ subgroup, 11/162 (6.8%), 78/302 (25.8%) and 89/323 (27.6%) patients were treated with a CDK4/6 inhibitor in the HER2+, HER2-low and HER2-0 subgroup, respectively. Conclusion: Low-HER2 expression did not have any impact on prognosis or choice of treatment in metastatic breast cancer in this real-world population.

Table 1HER2-positive (IHC 3+ or ISH+)HER2-low (IHC1+ or 2+ and ISH-)completely HER2-negative (IHC 0)All (n=1,079)262 (24.3%)372 (34.5%)445 (41.2%)HR+ (n=787)162 (20.6%)302 (38.4%)323 (41.0%)HR- (n=292)100 (34.2%)70 (24.0%)122 (41.8%)

Table 2HER2+ months (95%CI)HER2-low months (95%CI)HER2-0 months (95%CI)Log-rankPMedian OSAll (n=1,079)42.7 (32.5-52.9)32.2 (27.3-37.1)30.8 (26.0-35.7)0.007HR+ (n=787)49.6 (40.1-59.1)35.8 (31.4-40.2)40.5 (35.4-45.5)0.120HR- (n=292)26.4 (19.9-33.0)16.8 (12.9-20.7)14.3 (10.0-18.6)&lt; 0.001Median 1st-line PFS All (n=913)*12.4 (10.1-14.8)11.0 (9.3-12.7)11.3 (9.6-12.9)0.123HR+ (n=684)*14.6 (10.8-18.4)12.4 (10.3-14.5)14.7 (12.1-17.4)0.348HR- (n=229)*11.0 (8.2-13.9)5.6 (3.9-7.2)6.0 (4.4-7.5)&lt; 0.001* only patients with at least one line of therapy for metastatic disease and sufficiently documented medical records allowing calculation of PFS were included.

Citation Format: Simon Peter Gampenrieder, Gabriel Rinnerthaler, Andreas Petzer, Christoph Tinchon, David Fuchs, Marija Balic, Sonja Heibl, Holger Rumpold, Daniel Egle, August Felix Zabernigg, Christian Fridolin Singer, Johannes Andel, Michael Hubalek, Michael Knauer, Richard Greil. Landscape of HER2-low metastatic breast cancer (MBC): Results from the AGMT-MBC-Registry [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 P3-08-29.