Treatment of brain metastases in patients with HER2+ breast cancer

Abstract

Brain metastases are a frequent complication of cancer. However, effective treatments are available. This article aims to review clinical aspects of patients with brain metastases discussing the various treatment options for such patients. It will address the importance and significance of brain metastases in patients with breast cancer and, finally, review the problem of brain metastasis associated with human epidermal growth factor receptor 2-positive (HER2+) breast cancer. With ever-improving survival rates of patients with cancer, there is a greater likelihood that many will develop brain metastases. Treatments such as whole brain or stereotactic radiotherapy and surgery have been shown to be effective against brain metastases. In HER2+ breast cancer, trastuzumab has been shown to be very effective, although it cannot cross the blood-brain barrier. If patients with breast cancer who are being treated with trastuzumab and are responding systemically, develop brain metastases, then patient prognosis does need to be taken into account; however, maintaining treatment with trastuzumab while using available therapies to treat intracranial lesions should be considered as an option.

Development of nanotheranostics against metastatic breast cancer — A focus on the biology & mechanistic approaches

“…Brain metastatic tumors are aggressive in nature and are often associated with lung or liver metastasis. Women with brain metastatic disease suffer from headache, seizures and cognitive dysfunction with disturbances in consciousness and often die due to neurological disorders (Wadasadawala et al Bravo, 2009;Hinton et al, 2010;Hambrecht et al, 2011). Although complications associated with breast cancer metastasis vary from metastatic organ to organ, the symptoms mainly depend on the degree to which the cancer spreads.…”

The Role of Astrocytes in Tumor Growth and Progression

“…The most common type of brain metastases originate from lung cancer, accounting for up to 56% of brain metastases, followed by breast cancer metastases at 13-30% [32,33]. Interestingly, specific subtypes of these tumors have a much higher frequency of brain metastases, including non-small cell lung cancer (NSLC), triple negative breast cancer cells that are estrogenic receptor (ER), progesterone receptor (PR) and epidermal growth factor receptor-2 (HER2) (ER [32][33][34][35]. One theory behind a specific tumors' proclivity to the brain is explained by Paget's seed and soil hypothesis, which suggests that for a seed (tumor cell) to take up in a soil (brain), it must adapt itself and make changes that will favor the soil [26,36].…”

Pathogenesis of Breast Cancer Metastasis to Brain: a Comprehensive Approach to the Signaling Network

“…From the figure, we can see that BCBM is influenced by several genes and signaling pathways. Potentially, inhibition of these pathways can be a valuable therapeutic approach, especially early signaling pathways, because of this approach leads to inhibit more of accessory signaling pathways involved in progression of metastasis the possibility of metastasis from other organs especially breast should always be noted [95]. The biology of the primary tumor, the number and location of metastatic lesions, and the phase of systemic disease are important considerations for the treatment of brain metastasis [34].…”

“…When it comes to the diagnosis of brain metastases, MRI is the ideal test [95]. Molecular diagnosis may also be useful, for example, miR-205 that is negatively regulated by HER2/neu overexpression and miR-342 that is involved in the breast tumor's invasive behavior, these may be used as potential biomarkers for diagnosis of triple-negative breast cancer [96].…”

“…This interaction suppresses signal transduction pathways that regulate cell growth, survival, migration, differentiation, and angiogenesis, thereby decreases malignancy [16,101] and also increases the sensitivity of tumor cells to both endocrine therapy and certain chemotherapeutic agents [16]. Lapatinib inhibits the dual epidermal growth factor receptor and HER2 tyrosine kinase [95] and corresponding downstream signaling proteins and therefore cell proliferation and migration [102]. In targeted therapy of metastasis, inhibition of early signaling pathways is important, because this approach would be associated with inhibition of more accessory signaling pathways involved in progression of metastasis.…”