Brain metastases (BM) in patients treated with trastuzumab for HER2 overexpressing metastatic breast cancer (MBC): Incidence and survival

Stemmler, Joachim; Kahlert, S.; Siekiera, Wolfgang; Untch, Michael; Heinrich, Bernhard

doi:10.1200/jco.2005.23.16_suppl.1568

Cited by 9 publications

(5 citation statements)

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“…Several studies have also found a higher incidence of brain metastases in patients treated with trastuzumab, further supporting the hypothesis that ErbB-2-overexpressing breast cancer may have a predilection for metastasizing to the brain [63,64]. Stemmler and colleagues have investigated why ErbB-2-overexpressing metastatic breast cancer patients receiving trastuzumab suffer from an increased risk for developing brain metastases, even though visceral disease might be responsive to trastuzumab, and had failed local therapy [65,66]. They found that while trastuzumab was effective in treating liver and lung metastases, approximately one third of ErbB-2-overexpressing metastatic breast cancer patients develop brain metastases.…”

Section: Brain Metastasesmentioning

confidence: 93%

“…They found that while trastuzumab was effective in treating liver and lung metastases, approximately one third of ErbB-2-overexpressing metastatic breast cancer patients develop brain metastases. This observation suggests that the bloodbrain barrier prevents trastuzumab from reaching adequate concentrations in the central nervous system (CNS) [65,66]. Therefore, clinical trials have been carried out with lapatinib for the treatment of brain metastases because it is a small molecule able to penetrate the blood-brain barrier.…”

Section: Brain Metastasesmentioning

confidence: 99%

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Lapatinib: Current Status and Future Directions in Breast Cancer

2006

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Lapatinib is an oral receptor tyrosine kinase inhibitor, targeting both the ErbB-1 and ErbB-2 receptors. Preclinical in vitro and in vivo models indicate that lapatinib is active as monotherapy, synergistically in combination with trastuzumab, and in trastuzumab-resistant cell lines. Early clinical trials also provide evidence in patients that lapatinib is active against breast cancer. This paper reviews results of phase II and III clinical trials of lapatinib in metastatic breast cancer, evidence for its potential in patients with brain metastases, and current clinical trials as adjuvant treatment in earlystage disease. Our improved understanding of the biology of breast cancer and the use of biomarkers for identification of specific subtypes is allowing us to bring patient-specific novel therapies such as lapatinib to the clinic.

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Section: Brain Metastasesmentioning

confidence: 93%

Section: Brain Metastasesmentioning

confidence: 99%

Lapatinib: Current Status and Future Directions in Breast Cancer

2006

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“…Independent of other factors, positive HER2 status alone has been associated with a higher risk of developing central nervous system (CNS) involvement in spite of trastuzumab therapy [42,43]. This complication is presumably related, in part, to the poorer penetration of the antibody across the blood-brain barrier.…”

Section: Her2 Resistancementioning

confidence: 97%

Targeting HER 1 and 2 in breast cancer with lapatinib

Higa

2008

Oncol Rev

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Numerous clinical trials support the biological relevance of the HER2 oncoprotein in breast cancer. In spite of improved outcomes, overexpression of the receptor is associated with increased risks of disease relapse, even in patients with early, and potentially curable, disease. Until recently, development of resistance to trastuzumab left patients with no therapeutic option other than specifically targeted HER2. This paper provides an in-depth review of lapatinib, a dual HER kinase inhibitor, as well as some insight into three HER family members, in breast cancer.

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“…Studies have shown that although trastuzumab is effective in treating liver and lung metastases, approximately one third of HER2-overexpressing metastatic breast cancer patients develop brain metastases [17,18]. This observation suggests that trastuzumab is unable to cross the blood brain barrier.…”

Section: Studies In Breast Cancermentioning

confidence: 99%

Lapatinib: a novel dual tyrosine kinase inhibitor

Pickering

Ellis

2007

Targ Oncol

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Lapatinib is an active and well-tolerated oral dual tyrosine kinase inhibitor that is able to inhibit epidermal growth factor receptor (EGFR) and HER2 with high specificity. It has shown promising activity in several cancers most notably metastatic breast cancer. Lapatinib is active in both trastuzumab-refractory and -naïve breast cancer and a number of phase III studies are ongoing to fully define its activity. Studies have also been conducted in a range of other cancers including renal cell carcinoma. It is essential that future studies incorporate predictive biomarker subgroup analysis. This will help to ensure that important subgroup activity is not missed and also allow the definition of groups most likely to benefit from lapatinib.

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Brain metastases (BM) in patients treated with trastuzumab for HER2 overexpressing metastatic breast cancer (MBC): Incidence and survival

Cited by 9 publications

References 0 publications

Lapatinib: Current Status and Future Directions in Breast Cancer

Lapatinib: Current Status and Future Directions in Breast Cancer

Targeting HER 1 and 2 in breast cancer with lapatinib

Lapatinib: a novel dual tyrosine kinase inhibitor

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