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Risk factors for brain relapse in HER2-positive metastatic breast cancer patients

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Abstract

Brain relapse is a common occurrence in HER2-positive breast cancer patients. However, the factors determining the risk of brain metastasis in these patients remain to be established. The aim of this study was to assess the impact of particular clinical and pathological factors on the risk of brain relapse in HER2-positive advanced breast cancer patients. The study group included 264 consecutive HER-2 positive metastatic breast cancer patients, most of whom (210; 80%) were administered trastuzumab, usually in combination with chemotherapy. Time from the diagnosis to distant relapse ranged from 0 to 142 months (median 16 months). The most common dominant site of metastatic disease was viscera (80%), followed by soft tissue (11%) and bones (10%). After a median follow-up of 3.1 years, the symptomatic brain relapse occurred in 103 patients (39%). Median time from treatment dissemination to brain relapse was 15 months (range, 0–81 months), and the cumulative 1-year, 3-year and 5-year risk of brain relapse was 17, 42 and 55%, respectively. The average annual risk of brain relapse for surviving patients during consecutive 7 years of follow-up was 10.0% (95% CI, 6.6–13.5%). In the univariate analysis the only variable significantly related to the increased risk of brain relapse was time from initial diagnosis to distant relapse shorter than 2 years (HR = 1.55, 95% CI, 1.03–2.33, P = 0.034). Patients with dominant site of disease in soft tissue or bones tended to have lower risk of relapse (HR = 0.54 and 0.62; P = 0.098 and 0.203, respectively) compared to patients with visceral metastases. Treatment with trastuzumab was not associated with reduced risk of brain relapse (HR = 0.91, 95% CI, 0.47–1.77, P = 0.78). In the multivariate analysis, time from initial diagnosis to distant relapse shorter than 2 years remained the only significant variable related to increased risk of brain relapse (adjusted HR = 1.62, 95% CI, 1.07–2.44; P = 0.022). HER2-positive breast cancer patients remain at high and continuous risk of brain relapse for a prolonged period of time after diagnosis of disease dissemination. Short time from initial diagnosis to distant relapse is related to increased risk of brain relapse. Molecular predictors are sorely needed to better characterize patients with high probability of early brain relapse.

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Acknowledgments

The authors wish to thank Prof. Jacek Jassem for his contribution to study design, interpretation of results and numerous helpful discussions on the manuscript.

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Authors and Affiliations

  1. Department of Oncology, Military Institute of Medicine, Warsaw, Ul. Szaserów 128, 00-908, Warsaw, Poland

    Renata Duchnowska & Cezary Szczylik

  2. Medical University of Gdańsk, Gdańsk, Poland

    Rafał Dziadziuszko, Barbara Szostakiewicz & Katarzyna Sosińska-Mielcarek

  3. Regional Cancer Center, Białystok, Poland

    Bogumiła Czartoryska-Arłukowicz

  4. Regional Oncology Center, Opole, Poland

    Barbara Radecka

  5. Regional Oncology Hospital, Szczecin, Poland

    Agnieszka Karpińska

  6. Regional Oncology Center, Lublin, Poland

    Elżbieta Starosławska & Tomasz Kubiatowski

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  1. Renata Duchnowska
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  2. Rafał Dziadziuszko
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  3. Bogumiła Czartoryska-Arłukowicz
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Correspondence to Renata Duchnowska.

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Presented in part in oral form at the 2007 European Cancer Conference, Barcelona, Spain.

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Duchnowska, R., Dziadziuszko, R., Czartoryska-Arłukowicz, B. et al. Risk factors for brain relapse in HER2-positive metastatic breast cancer patients. Breast Cancer Res Treat 117, 297–303 (2009). https://doi.org/10.1007/s10549-008-0275-z

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