Abstract P1-19-34: The role of hormone receptor (HR) status on initial treatment choices and outcomes for human epidermal growth factor receptor (HER)-2 positive advanced breast cancer: A study of the southeast Netherlands advanced breast cancer (SONABRE) registry
Authors: Geurts Sandra M.E. , Ibragimova Khava I.E. , Teeuwen Nathalie JA , Erdkamp Frans , Vriens Birgit EPJ , den Boer Marien O , Dercksen M Wouter , Pepels Manon JAE , de Boer Maaike , Tjan-Heijnen Vivianne CG 
Published: March 2020

Abstract
Background Previously, we reported that patients with HR+/HER2+ advanced breast cancer diagnosed in 2007-2009 had a better overall survival (OS) than patients with HR-/HER2+ advanced breast cancer (SONABRE Registry, Lobbezoo et al. BCRT 2013). This differential outcome suggests an impact of biology and/or used systemic therapies. The objective of the current study was to present initial palliative systemic therapy choices and its impact on OS and progression-free survival (PFS) in patients diagnosed with HER2+ advanced breast cancer in the Netherlands in 2007-2017, stratified by HR status. Patients and methods From our ongoing SONABRE Registry, we selected all consecutive patients diagnosed with HER2+ advanced breast cancer in six hospitals in the Netherlands in 2007-2017. OS and PFS by HR status were obtained using the Kaplan-Meier method and compared by the log-rank test. The multivariable Cox proportional hazards model for OS and PFS on initial systemic therapy were stratified by HR status and included the potential prognostic variables age, cardiovascular disease, metastatic-free interval, initial metastatic sites, (neo-) adjuvant therapy and (type of) initial palliative systemic therapy. Results Of the 376 patients included, 221 (59%) patients were diagnosed with HR+/HER2+ and 155 (41%) with HR-/HER2+ advanced breast cancer. Patients with HR+/HER2+ disease were most frequently diagnosed with bone metastases (74%), whereas the majority of patients with HR-/HER2+ disease were diagnosed with visceral metastases (66%) as initial dominant metastatic site. Of patients with HR+/HER2+ disease, 95% received at least one line of palliative systemic therapy among which 56% initially included HER2-targeted based therapy. Among patients with HR-/HER2+ disease, 77% received systemic therapy of which 87% initially included HER2-targeted based therapy. Median OS was 29 months (95% CI: 24-34) for HR+/HER2+ and 17 months (95% CI: 14-22) for HR-/HER2+ disease (logrank p=0.03). In patients with HR+/HER2+ disease, initial endocrine therapy without HER2-targeted therapy (n=80) did not significantly impact OS (hazard ratio: 1.12, 95% CI: 0.75-1.68), even though it was associated with a shorter initial PFS (hazard ratio: 1.48, 95% CI: 0.94-2.34) when compared with initial HER2-targeted therapy plus chemotherapy (n=81). On the other hand, in patients with HR-/HER2+ disease, receiving initial chemotherapy without HER2-targeted therapy (n=15) was associated with a shorter OS (hazard ratio:2.15, 95% CI 1.11-4.16) and PFS (hazard ratio =3.15, 95% CI 1.37-7.24) when compared with receiving initial HER2-targeted therapy plus chemotherapy (n=97). Conclusions In this extended real-life study with a long follow-up, we confirmed our previous findings that among patients with HER2+ advanced breast cancer the HR+ subtype had a more favorable outcome. We were able to show a differential metastatic pattern by HR status underlining its biological relevance. Immediate use of HER2-targeted therapy had no statistically significant positive effect on OS in the HR+ subtype, in contrast to the positive effect of immediate HER2-targeting therapy in the HR- subtype. Translational studies are warranted to shed more light on the cross-talk between the HR and HER2 pathways to improve selection for HER2-targeted therapies.
Citation Format: Sandra M.E. Geurts, Khava I.E. Ibragimova, Nathalie JA Teeuwen, Frans Erdkamp, Birgit EPJ Vriens, Marien O den Boer, M Wouter Dercksen, Manon JAE Pepels, Maaike de Boer, Vivianne CG Tjan-Heijnen. The role of hormone receptor (HR) status on initial treatment choices and outcomes for human epidermal growth factor receptor (HER)-2 positive advanced breast cancer: A study of the southeast Netherlands advanced breast cancer (SONABRE) 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 P1-19-34.