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: 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.
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