Abstract 95MO
Background
About 40% of patients with a metastatic HER2+ breast cancer (BC) develop brain metastases (BM). A better understanding of clinical features of patients with HER2+ BC with BM is required.
Methods
A total of 2948 patients of the Brain Metastases in Breast Cancer (BMBC) Registry were available for this analysis, 1311 of them had a HER2+ subtype.
Results
Patients with a HER2+ BC and BM were,compared to HER2- patients, slightly younger at BC diagnosis (median 52 vs 53 years, p<0.001) and BM diagnosis (median 55 vs 58 years, p<0.001), had a higher pathological complete response rate after neoadjuvant chemotherapy (21.5 vs 12.2%, p=0.002), higher tumor grading (G3 59.5 vs 56.5%, p<0.001) and had less common extracranial metastases (ECM) at BM diagnosis (77.7 vs 80.0%, p<0.001). HER2+ patients had significantly more often BM in the posterior fossa (57.9 vs 49.0%, p<0.001) but less common leptomeningeal metastases (LM) (9.3 vs 19.1%, p<0.001). Hormone-receptor-positive HER2+ patients were younger at BC diagnosis (median 50 vs 53 years, p=0.03), had a smaller initial BC (<5cm: 78.4 vs 66.3%, p=0.002), a lower grading of the primary tumor (G1/G2: 46.1 vs 29.9%, p<0.001) and more often LM (11.3 vs 6.8%, p=0.007). The median overall survival (OS) in all HER2+ patients was 13.2 months (95% CI 11.4-14.4). The following factors were associated with a worse OS (multivariate analysis): older age (≥60 vs <60 years: Hazard Ratio [HR] 1.63, p<0.001), lower performance status (ECOG 2-4 vs 0-1: HR 1.58, p<0.001), greater number of BM (2-3 vs 1 BM: HR 1.36; ≥4 vs 1 BM: HR 1.53, p=0.003; overall p=0.012), BM in fossa anterior (HR 1.71, p<0.001), LM (HR 1.62, p=0.027), BM with neurological symptoms at diagnosis (HR 1.38, p=0.029), ECM at diagnosis of BM (HR 1.44, p=0.02) and the absence of targeted therapy (HR 0.625, p=0.001). Although progression-free survival did not differ in HER2+ patients according to hormone-receptor status, a significantly better OS could be observed for hormonereceptor-positive patients (median 14.3 vs 10.9 months, p=0.027).
Conclusions
The performed analysis identified factors associated with prognosis of HER2+ patients with BM. Further research is needed to understand the factors determining the longer survival of HER2+ hormonereceptor-positive patients.
Legal entity responsible for the study
German Breast Group Forschungs GmbH.
Funding
Has not received any funding.
Disclosure
I. Witzel: Honoraria (institution): Amgen; Honoraria (institution): AstraZeneca; Honoraria (institution): MSD; Honoraria (institution): Novartis; Honoraria (institution): Pierrre Fabre Pharma; Honoraria (institution): Pfizer; Honoraria (institution): Roche; Honoraria (institution): Sanofi-Pfizer. C. Denkert: Honoraria (institution), Oncobiome project: European Commission H2020; Honoraria (institution), INTEGRATE-TN project: German Cancer Aid Translational Oncology; Honoraria (self): Novartis; Honoraria (self): Roche; Honoraria (self): MSD Oncology; Honoraria (self): Daiichi Sankyo; Honoraria (self): AstraZeneca; Honoraria (self): Molecular Health; Honoraria (institution): Myriad; Honoraria (self): Merck; Shareholder/Stockholder/Stock options, Cofounder/shareholder until 2016: Sividon diagnostics; Licensing/Royalties: VMScope digital pathology software; Licensing/Royalties: WO2020109570A1 - cancer immunotherapy; Licensing/Royalties: WO2015114146A1 and WO2010076322A1- therapy response. S. Loibl: Honoraria (institution), honoraria for lectures and ad boards paid to institute: AbbVie; Honoraria (institution), honoraria for lectures and ad boards paid to institute: Celgene; Honoraria (institution), honorarium for lectures paid to institute: PriME/Medscape; Honoraria (self), lecture: Chugai; Honoraria (self), Honoraria (institution), honoraria paid to institute: Daiichi Sankyo; Honoraria (institution), honorarium for ad boards paid to institute: Lilly; Honoraria (institution), advisor honorarium paid to institute: BMS; Honoraria (institution), advisor honorarium paid to institute: Puma; Honoraria (institution), paid to institute: Immunomedics; Honoraria (institution), honorarium for lectures and ad boards paid to institute: AstraZeneca; Honoraria (institution), honorarium for lectures and ad boards paid to institute: Pierre Fabre; Honoraria (institution), honorarium for lectures and ad boards paid to institute: Merck; Honoraria (institution), advisor honorarium paid to institute: EirGenix; Honoraria (institution), honorarium for lectures and ad boards paid to institute: Amgen; Honoraria (institution), honorarium for lectures and ad boards paid to institute: Novartis; Honoraria (institution), honorarium for lectures and ad boards paid to institute: Pfizer; Honoraria (institution), grant and honorarium paid to institute: Roche; Honoraria (institution), paid to institute: Seagen; Licensing/Royalties, Immunsignature in TNBC: EP14153692.0. V. Mueller: Advisory/Consultancy: Genomic Health, Hexal, Roche, Pierre Fabre, Amgen, ClinSol, Novartis, MSD, Daiichi Sankyo, Eisai, Lilly, Tesaro and Nektar; Speaker Bureau/Expert testimony: Amgen, AstraZeneca, Daiichi Sankyo, Eisai, Pfizer, MSD, Novartis, Roche, Teva, Seagen and consultancy honoraria from Genomic Health, Hexal, Roche, Pierre Fabre, Amgen, ClinSol, Novartis, MSD, Daiichi Sankyo, Eisai, Lilly, Tesaro, Nektar; Honoraria (institution): Novartis, Roche, Seattle Genetics, Genentech. All other authors have declared no conflicts of interest.