Brain metastases in HER2-positive breast cancer: The evolving role of lapatinib

Institut Jules Bordet, Université Libre de Bruxelles, 121 Boulevard de Waterloo, 1000, Brussels, Belgium.
Critical reviews in oncology/hematology (Impact Factor: 4.03). 12/2009; 75(2):110-21. DOI: 10.1016/j.critrevonc.2009.11.003
Source: PubMed


Due to improvements in diagnosis and systemic therapy, brain metastases are an increasingly common cause of morbidity and mortality for patients with advanced breast cancer. The incidence of symptomatic brain metastases among women with metastatic breast cancer ranges from 10% to 16%. The HER2 receptor, which is overexpressed in approximately 25% of all breast cancers, is an important risk factor for the development of central nervous system metastases. Surgery and radiation therapy are the primary approaches to the treatment of brain metastases but new chemotherapy and biological agents promise to play an important role in the future management of central nervous system disease. This article reviews the epidemiology, current treatment options and recent advances in the field, with a focus on HER2-positive disease and the emerging role of lapatinib for the treatment and prevention of brain metastases.

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Available from: Gianluca Tomasello, Sep 11, 2015
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    • "On the other hand, prevention from BM is important too. Many risk factors are associated with the development of BM, such as young age, hormone receptor-negative primary tumors, HER2+ tumors, and heavy burden of disease (large primary tumors, lymph node involvement, prior lung, liver, or bone metastases, increased number of metastatic sites, and elevated lactate dehydrogenase [LDH] levels) [1]. In breast cancer patients with high risk of brain metastasis, wholebrain irradiation may be studied in controlled clinical trials. "
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    ABSTRACT: Trastuzumab treatment does not prevent intracranial seeding and is largely ineffective for established central nervous system metastasis in HER2 overexpressing breast cancer patients. Combination therapy of lapatinib and capecitabine may be an effective treatment option for brain metastasis of HER2-positive breast cancer. We report a patient with breast cancer overexpressing HER-2 where brain metastases were successfully treated with radiation and a combination of lapatinib and capecitabine.
    Full-text · Article · Sep 2013 · Case Reports in Oncological Medicine
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    • "The median survival from first admission with brain metastases was only a few months, also in line with other studies (Lin and Winer, 2007; Tomasello et al, 2010). Breast cancer characteristics associated with more aggressive disease, ER and PR negativity and HER-2 overexpressing tumours (Gutierrez and Schiff, 2011; Stuckey, 2011) have been associated with an increased risk of brain metastases (Lin and Winer, 2007; Tomasello et al, 2010). Adjuvant anti-HER-2 antibody treatment, trastuzumab was introduced in 2000 and was gradually adopted in Sweden. "
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    ABSTRACT: While treatment for breast cancer has been refined and overall survival has improved, there is concern that the incidence of brain metastases has increased. We identified patients in Sweden with incident breast cancer 1998-2006 in the National Cancer Register, and matched these to the National Patient Register to obtain information on hospital admissions for distant metastases. Hazard ratios (HRs) and 95% confidence intervals (CIs) were computed with Cox regression as estimates of relative risk. Among 50 528 breast cancer patients, 696 (1.4%) were admitted with brain metastases during median 3.5 years of follow-up. Admissions for other metastases were found in 3470 (6.9%) patients. Compared with the period 1998-2000, patients diagnosed with breast cancer 2004-2006 were at a 44% increased risk of being admitted with brain metastases (HR 1.44, 95% CI 1.13-1.85). The incidence of admissions with brain metastases in breast cancer patients was increasing in the mid-2000s in Sweden. These findings support a true increase in incidence of brain metastases among breast cancer patients.
    Preview · Article · Apr 2012 · British Journal of Cancer
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    ABSTRACT: Lapatinib is an oral dual erbB 1/2 tyrosine kinase inhibitor that inhibits human EGF receptor 2 (HER2) and blocks the EGF receptor. Studies have shown that in patients with metastatic HER2-positive breast cancer that is resistant to trastuzumab, the addition of lapatinib to capecitabine improves progression-free survival and appears to lengthen overall survival. Furthermore, lapatinib has been studied in patients with involvement of the CNS and has been associated with stable disease and some responses. Its combination with letrozole provided an improvement in progression-free survival compared with single-agent letrozole in women with hormone receptor-positive, HER2-positive metastatic breast cancer. More recently, data suggested that the combination of lapatinib with trastuzumab significantly improves overall survival in women with metastatic breast cancer compared with single-agent lapatinib. Current indications in the USA for the use of lapatinib are for the treatment of metastatic HER2-positive breast cancer, both in combination with capecitabine in patients who have received taxane, anthracycline and traztuzumab, and in combination with letrozole for postmenopausal patients with hormone receptor- and HER2-overexpressing breast cancer. Common side effects of lapatinib include diarrhea and rash. Studies to date have found a less than 2% risk for cardiotoxicity, although most cardiac events that occurred during the studies were not attributed to lapatinib. It is important to consider that most of the patients in existing studies had already been treated with trastuzumab with no significant cardiotoxicity; therefore, future studies will show how trastuzumab-naive patients tolerate lapatinib. Ongoing research is evaluating the role of lapatinib in the adjuvant setting as a single agent or in combination with trastuzumab.
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