Central Nervous System Metastases in HER-2–Overexpressing Metastatic Breast Cancer: A Treatment Challenge

Stemmler, Hans-Joachim; Heinemann, Volker

doi:10.1634/theoncologist.2008-0052

Cited by 58 publications

(53 citation statements)

References 78 publications

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“…Recently, these drugs have been exploring the potential role in patients with estrogen receptor (ER) positive BCBM 112. A phase II study is evaluating the safety and activity of abemaciclib in hormone receptor (HR) positive BCBM and lung cancer or melanoma with BM 113. Vimentin and Snail, known as the EMT markers, could be downregulated with palbociclib treatment,114 supporting its inhibition of migration and invasion of breast cancer cells.…”

Section: The Mechanism Of Brain Metastasismentioning

confidence: 99%

Emerging findings into molecular mechanism of brain metastasis

Chen

2018

Cancer Medicine

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Brain metastasis is an important cause of morbidity and mortality in cancer patients. Hence, the need to develop improved therapies to prevent and treat metastasis to the brain is becoming urgent. Recent studies in this area are bringing about some advanced progress on brain metastasis. It was concluded that the occurrence and poor prognosis of brain metastasis have been mostly attributed to the exclusion of anticancer drugs from the brain by the blood‐brain barrier. And several highly potent new generation targeted drugs with enhanced CNS distribution have been developed constantly. However, the noted “seed and soil” hypothesis also suggests that the outcome of metastasis depends on the relationship between unique tumor cells and the specific organ microenvironment. Moreover, increasing studies in multiple tumor types demonstrated that brain metastasis has great molecular differences between primary tumors and extracranial metastasis to a large extent. Here, the authors summarized the most common malignancies that could lead to brain metastasis—lung cancer, breast cancer and melanoma and their related mutated factors. Only by comprehending a deeper understanding of the molecular mechanisms, more effective brain‐specific therapies will be developed for brain metastasis.

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Section: The Mechanism Of Brain Metastasismentioning

confidence: 99%

Emerging findings into molecular mechanism of brain metastasis

Chen

2018

Cancer Medicine

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“…1,2 Recent reports have raised the possibility of a growing incidence of CNS metastasis in patients with breast cancer. 3,4 On the basis of retrospective observations, risk factors for the development of CNS metastases from breast cancer include patient characteristics such as young age and African-American ethnicity, and biological features of the tumor, including estrogen receptor (ER) negativity, human epidermal growth factor receptor 2 (HER2) positivity, high tumor grade, and BRCA1 phenotype. 1,[5][6][7][8][9][10][11][12][13][14][15][16] HER2 (Her-2/neu, c-erbB-2) is a 185-kilodalton transmembrane tyrosine kinase with extensive homology to the epidermal growth factor receptor.…”

mentioning

confidence: 99%

“…3,[13][14][15][16] However, other studies have obtained opposite results, demonstrating no association between HER2 status and CNS recurrence. 4,19,20 The humanized anti-HER2 monoclonal antibody trastuzumab is an effective treatment of patients with HER2-positive breast cancer. 21 However, soon after the introduction of trastuzumab in the late 1990s, clinicians began to observe an apparent increase in the incidence of CNS metastases over historical controls.…”

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confidence: 99%

Multifactorial central nervous system recurrence susceptibility in patients with HER2‐positive breast cancer

Musolino¹,

Ciccolallo²,

Panebianco³

et al. 2010

Cancer

118

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BACKGROUND: A series of retrospective studies have reported that patients with human epidermal growth factor receptor 2(HER2)-positive breast cancer are at a greater risk of central nervous system (CNS) metastases. Trastuzumab, which does not cross the blood-brain barrier, has been associated with this increased risk. METHODS: The authors evaluated incidence, survival, and risk factors for CNS metastases in the incident breast cancer population systematically collected by the Parma Province Cancer Registry over the 4-year period between 2004 and 2007. RESULTS: A total of 1458 patients with a diagnosis of stage I to III invasive breast cancer were analyzed for study purposes. At a median follow-up of 4.1 years, CNS events were observed in 1.3% and 5% of HER2-negative patients and HER2-positive patients, respectively (P < .0001). The administration of trastuzumab either as adjuvant therapy or for metastatic disease was associated with a significantly increased risk of CNS involvement at first disease recurrence and after first extracranial recurrence, respectively. According to multivariate analysis, HER2-positive status and trastuzumab treatment, high Ki-67 index, and hormone receptor negativity remained independent risk factors for the development of CNS metastasis. CONCLUSIONS: To the authors' knowledge, this is the first population-based cancer registry study analyzing factors associated with CNS recurrence in a general population of newly diagnosed breast cancer patients with known HER2 status. The data from the current study provide evidence that patients with HER2-positive breast cancer have a significantly higher incidence of CNS metastasis after treatment with trastuzumab. Improvements in systemic control and overall survival associated with trastuzumab-based therapy may lead to an ''unmasking'' of CNS disease recurrence that would otherwise remain clinically silent before a patient's death.

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“…Additionally, it may be argued that trastuzumab-based therapy prolongs survival to such an extent that BM, which is known to be a late event in the course of metastatic cancer, becomes apparent. The higher incidence of BM could be interpreted as a result of the prolonged duration of the disease (Stemmler and Heinemann, 2008).…”

mentioning

confidence: 99%

Trastuzumab treatment improves brain metastasis outcomes through control and durable prolongation of systemic extracranial disease in HER2-overexpressing breast cancer patients

et al. 2009

Br J Cancer

161

107

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In patients with human epidermal growth factor receptor-2 (HER2)-overexpressing breast cancer, treatment with trastuzumab has been shown to markedly improve the outcome. We investigated the role of trastuzumab on brain metastasis (BM) in HER2-positive breast cancer patients. From 1999 to 2006, 251 patients were treated with palliative chemotherapy for HER2-positive metastatic breast cancer at Samsung Medical Center. The medical records of these patients were analysed to study the effects of trastuzumab on BM prevalence and outcomes. Patients were grouped according to trastuzumab therapy: pre-T (no trastuzumab therapy) vs post-T (trastuzumab therapy). The development of BM between the two treatment groups was significantly different (37.8% for post-T vs 25.0% for pre-T, P ¼ 0.028). Patients who had received trastuzumab had longer times to BM compared with patients who were not treated with trastuzumab (median 15 months for post-T group vs 10 months for pre-T group, P ¼ 0.035). Time to death (TTD) from BM was significantly longer in the post-T group than in the pre-T group (median 14.9 vs 4.0 months, P ¼ 0.0005). Extracranial disease control at the time of BM, 12 months or more of progression-free survival of extracranial disease and treatment with lapatinib were independent prognostic factors for TTD from BM.

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Central Nervous System Metastases in HER-2–Overexpressing Metastatic Breast Cancer: A Treatment Challenge

Cited by 58 publications

References 78 publications

Emerging findings into molecular mechanism of brain metastasis

Emerging findings into molecular mechanism of brain metastasis

Multifactorial central nervous system recurrence susceptibility in patients with HER2‐positive breast cancer

Trastuzumab treatment improves brain metastasis outcomes through control and durable prolongation of systemic extracranial disease in HER2-overexpressing breast cancer patients

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