Larsen, PB, Kümler, I and Nielsen, DL. A systematic review of trastuzumab and lapatinib in the treatment of women with brain metastases from HER2-positive breast cancer. Cancer Treat Rev 39: 720-727

Department of Oncology, Herlev Hospital, University of Copenhagen, Herlev Ringvej 75, DK-2730 Herlev, Denmark. Electronic address: .
Cancer Treatment Reviews (Impact Factor: 7.59). 03/2013; 39(7). DOI: 10.1016/j.ctrv.2013.01.006
Source: PubMed


Patients with HER2-positive breast cancer are living still longer and increasingly experiencing brain metastases. Current HER2-targeted therapies have limited potential to cross the blood-brain-barrier. We performed a systematic review to investigate data on HER2-targeting therapies in the treatment of brain metastases in breast cancer. We searched PUBMED for all human studies published 1998-2012 using the following search terms: breast neoplasm/cancer, human epidermal growth factor receptor 2/HER2, ErbB2, trastuzumab, lapatinib, brain/cerebral neoplasm/metastases and blood-brain barrier. We identified few and mostly small clinical studies. Study designs were very heterogeneous making comparisons on endpoints difficult. Overall survival for patients treated with trastuzumab varied from 8 to 25months and 5.5 to 11months for patients receiving lapatinib. The majority of studies were retrospective thus possibly biasing data. Only three studies were identified comparing trastuzumab to lapatinib. Conclusively, no solid data exist on how to treat patients with HER2-positive disease and brain metastases. Although continuous HER2-blockade is recommended by international consensus guidelines, it is still not evident which HER2-targeting agent should be preferred when brain metastases occur. The choice of chemotherapy to accompany the blockade is not obvious and we do not know if dual is better than single blockade. Further clinical trials are urgently needed.

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Available from: Pia Bükmann Larsen, Nov 17, 2014
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    • "Advances in systemic treatment have substantially improved the overall survival of advanced breast cancer patients [5,6], and brain metastases are emerging as an important sanctuary site. An increasing proportion of patients have been observed suffering from symptomatic brain metastases often at a time when their extracranial disease is apparently under control [5,7]. The survival of patients with symptomatic multiple brain metastases is poor even after palliative whole brain irradiation [8,9], and better in patients with brain oligometastases where surgical resection or stereotactic radiotherapy can be applied [10-13]. "
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    ABSTRACT: The objective of this study was to identify breast cancer patients with a high risk of developing brain metastases who may benefit from pre-emptive medical intervention. Medical records of 352 breast cancer patients with local or locoregional disease at diagnosis were retrospectively analysed. The brain metastasis-free survival was estimated using the Kaplan-Meier method and patient groups were compared using the log rank test. The simultaneous relationship of multiple prognostic factors was assessed using Cox's proportional hazard regression analysis. The Fisher exact test was used to test the difference of proportions for statistical significance. On univariate analysis, statistically highly significant unfavourable risk factors for the brain metastasis-free survival were negative ER status, negative PR status, and triple negative tumor subtype. Young age at diagnosis (<=35 years) and advanced disease stage were not statistically significant (p = 0.10). On multivariate analysis, the only independent significant factor was the ER status (negative ER status; hazard radio (95% confidence interval), 5.1 (1.8-14.6); p = 0.003). In the subgroup of 168 patients with a minimum follow-up of 24 months, 49 patients developed extracranial metastases as first metastatic event. Of those, 7 of 15 (46.6%) with a negative ER status developed brain metastases compared to 5 of 34 (14.7%) with a positive ER status (Fisher exact test, p = 0.03). The median time interval (minimum-maximum) between the diagnosis of extracranial and brain metastases was 7.5 months (1-30 months). Breast cancer patients with extracranial metastasis and negative ER status exhibited an almost 50% risk of developing brain metastasis during their course of disease. Future studies are highly desired to evaluate the efficacy of pre-emptive medical intervention such as prophylactic treatment or diagnostic screening for high risk breast cancer patients.
    Full-text · Article · Apr 2014 · BMC Cancer
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    ABSTRACT: A challenge in the management of breast cancer is development of brain metastases (BM) with limited survival. In primary breast cancer, ER/PR/HER2 are important prognostic markers and are important for making effective treatment decisions. Changes in immunohistochemical markers of metastases are with unclear clinical significance, and mechanisms of resistance to endocrine therapy are an additional challenge. The aim of this retrospective study is to detect changes in immunohistochemical markers of primary and BM and to recognize if receptor change has prognostic impact. Twenty-four consecutive primary breast cancer patients who developed BM and got surgical resection of BM were enrolled. Matched pair analyses of primary and BM were done with evaluation by immunostaining (ER/PR/HER2). A small tumor size, ductal histology and HER2+ tumors were associated with BM. Loss of ER/PR receptor positivity was observed in BM compared to primary (ER: 50.0 %/22.7 %; p = 0.004; PR: 45.8 %/9.1 %; p = n.s), respectively, and almost no change in HER2 status (>80 %; p = 0.012). Patients with ER-/PR-negative or HER2-positive primary had shorter time to recurrence than ER-/PR-positive and HER2-negative patients. Receptor change has negative prognostic impact. With the observed loss of receptor positivity, therapeutic options are diminished. Identification of patients with a high risk for BM is warranted to evaluate preventive strategies.
    No preview · Article · Sep 2013 · Journal of Cancer Research and Clinical Oncology
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    ABSTRACT: Breast cancer is the second leading cause of brain metastases and account for 15 % of metastatic breast cancer patients. Several patient- and tumor-related characteristics have been identified as risk factors for developing brain metastases. Treatment is based on local and/or systemic therapies, tailored to breast cancer brain metastases-specific prognostic factors. This article is an update on the current knowledge of the incidence, prognosis and prognostic factors, treatment and perspectives in brain metastases from breast cancer.
    No preview · Article · Nov 2013 · Cancer/Radiothérapie
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