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. 2020 Sep 28;12(10):2787.
doi: 10.3390/cancers12102787.

Characteristics and Clinical Outcome of Breast Cancer Patients with Asymptomatic Brain Metastases

Elena Laakmann  1 , Isabell Witzel  1 , Tanja Neunhöffer  2 , Rudolf Weide  3 , Marcus Schmidt  4 , Tjoung-Won Park-Simon  5 , Volker Möbus  6 , Christoph Mundhenke  7   8 , Arkadius Polasik  9 , Kristina Lübbe  10 , Tobias Hesse  11 , Kerstin Riecke  1 , Marc Thill  12 , Peter A Fasching  13 , Carsten Denkert  14 , Tanja Fehm  15 , Valentina Nekljudova  16 , Julia Rey  16 , Sibylle Loibl  16 , Volkmar Müller  1
Affiliations

Characteristics and Clinical Outcome of Breast Cancer Patients with Asymptomatic Brain Metastases

Elena Laakmann et al. Cancers (Basel). .

Abstract

Background: Brain metastases (BM) have become a major challenge in patients with metastatic breast cancer. Methods: The aim of this analysis was to characterize patients with asymptomatic BM (n = 580) in the overall cohort of 2589 patients with BM from our Brain Metastases in Breast Cancer Network Germany (BMBC) registry. Results: Compared to symptomatic patients, asymptomatic patients were slightly younger at diagnosis (median age: 55.5 vs. 57.0 years, p = 0.01), had a better performance status at diagnosis (Karnofsky index 80-100%: 68.4% vs. 57%, p < 0.001), a lower number of BM (>1 BM: 56% vs. 70%, p = 0.027), and a slightly smaller diameter of BM (median: 1.5 vs. 2.2 cm, p < 0.001). Asymptomatic patients were more likely to have extracranial metastases (86.7% vs. 81.5%, p = 0.003) but were less likely to have leptomeningeal metastasis (6.3% vs. 10.9%, p < 0.001). Asymptomatic patients underwent less intensive BM therapy but had a longer median overall survival (statistically significant for a cohort of HER2-positive patients) compared to symptomatic patients (10.4 vs. 6.9 months, p < 0.001). Conclusions: These analyses show a trend that asymptomatic patients have less severe metastatic brain disease and despite less intensive local BM therapy still have a better outcome (statistically significant for a cohort of HER2-positive patients) than patients who present with symptomatic BM, although a lead time bias of the earlier diagnosis cannot be ruled out. Our analysis is of clinical relevance in the context of potential trials examining the benefit of early detection and treatment of BM.

Keywords: asymptomatic; brain metastases; breast cancer.

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Conflict of interest statement

V.M. (Volkmar Müller) received speaker honoraria from Amgen, Astra Zeneca, Daiichi-Sankyo, Eisai, Pfizer, MSD, Novartis, Roche, Teva, Seattle Genetics and consultancy honoraria from Genomic Health, Hexal, Roche, Pierre Fabre, Amgen, ClinSol, Novartis, MSD, Daiichi-Sankyo, Eisai, Lilly, Tesaro, Seattle Genetics and Nektar. Institutional research support from Novartis, Roche, Seattle Genetics, Genentech. Travel grants: Roche, Pfizer, Daiichi Sankyo. M.T. is a member of advisory Board of Amgen, AstraZeneca, Celgene, Daiichi Sankyo, Eisai, Exact Sciences, Lilly, MSD, Novartis, onkowissen.de, Pfizer, Pierre-Fabre, Roche, he provides manuscript support for Amgen, Celgene, Roche, received travel reimbursement from Amgen, Art Tempi, AstraZeneca, Celgene, Connect Medica, Daiichi Sankyo, Eisai, Exact Sciences, Hexal, I-Med-Institute, Lilly, MCI, MSD, Novartis, Omniamed, Pfizer, Roche, congress support from Amgen, AstraZeneca, Celgene, Daiichi Sanyko, Hexal, Novartis, Pfizer, Roche. M.T. is involved in lecture by Amgen, Art Tempi, AstraZeneca, Celgene, Connect Medica, Eisai, Exact Sciences, Hexal, I-Med-Institute, Lilly, MCI, MSD, Novartis, onkowissen.de, Omniamed, Pfizer, Roche, Vifor. M.T. received trial funding by Exact Sciences. M.S. received honoraria for speaker or consultancy role from AMGEN, AstraZeneca, Eisai, Lilly, Myelo Therapeutics, Novartis, Pantarhei Bioscience, Pfizer, Roche and Seattle Genetics. He received research funding from AstraZeneca, BioNTech, Eisai, Genentech, German Breast Group, Myelo Therapeutics, Novartis, Palleos, Pantarhei Bioscience, Pierre-Fabre, and Roche. He received travel reimbursement from Pfizer and Roche. P.F. reports personal fees from Novartis, Roche, Pfizer, Daiichi-Sankyo, Astra Zeneca, Eisai, Merck Sharp & Dohme, Lilly, Pierre Fabre, Seattle, grants from Biontech, Cepheid, Genetics, during the conduct of the study. V. Möbus received speaker honoraria from Amgen, AstraZeneca, Celgene, Roche, Teva and consultancy honoraria from Roche, Amgen, Tesaro and Myelo Therapuetics. C.D. has stock and other ownership interests by Sividon Diagnostics (now Myriad), recieved honoraria by Novartis and Roche, has consulting or advisory role by MSD Oncology and Daiichi Sankyom, has patents, royalties or other intellectual property by VMScope digital pathology software, has two patents (patent application: EP18209672—cancer immunotherapy, patent application EP20150702464 - therapy response), received travel, accommodations, expenses from Roche, his institution received research funding by Myriad Genetics. S.L. has no conflict of interests concerning the presented analysis. S.L. has following relevant financial activities outside the submitted work (with conflict of interests): grants and honorario for lectures and ad boards paid to institute from Abbvie, Amgen, Celgene, Novartis, Pfizer, Roche; honorario for lectures and ad boards paid to institute from Seattle Genetics, Samsung, PriME/Medscape; personal fees for lecture from Chugai; grants from Teva, Vifor; grant and honorarium paid to institute from Daiichi-Sankyo; honorarium for ad boards paid to institute from Lilly; advisor honorarium paid to institute from Eirgenix, BMS, Puma; honorarium paid for institute from MSD, grant paid to institute from Immunomedics; grant and honorarium for lectures and ad boards paid to institute from Astra Zeneca. S.L. has intellectual property broadly relevant to the work (pending patent EP14153692.0 Immunsignature in TNBC). IW has no conflict of interest concerning the presented analysis, she received speaker‘s honoraria outside this work from Amgen, MSD, Novartis, Pierre Fabre Pharme, Pfizer, Roche, Sanofi-Aventis. Other authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Kaplan-Meier curves for the time from the diagnosis of breast cancer to the diagnosis of BM.
Figure 2
Figure 2
Kaplan-Meier curve for the time from first diagnosis of BM to death due to any reason.
Figure 3
Figure 3
Kaplan-Meier curve for the time from first diagnosis of BM to death due to any reason among HER2-positive patients.
See this image and copyright information in PMC

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