Occult central nervous system involvement in patients with metastatic breast cancer: prevalence, predictive factors and impact on overall survival

Although breast cancer is the second most common cause of central nervous system (CNS) metastases with a notable increase of incidence, only few studies on brain-metastasizing breast cancer are available. In this immunohistochemical and fluorescence in situ hybridization (FISH) study, metastases to the CNS (n ¼ 85) and primary breast cancers, with known involvement of the CNS (n ¼ 44) including paired primary and metastasized tumours (n ¼ 23), were investigated retrospectively for the expression of oestrogen-(ER) and progesterone-(PR) hormone receptors, Her-2/neu, epidermal growth factor receptor (EGFR), Ki-67, and cytokeratins (CKs) 5/ 14. The majority of brain metastases were steroid hormone receptor negative (ER 66%, PR 82%) corresponding to the findings in primary tumours with known involvement of the CNS (68% ER-negative, 75% PR-negative). The frequency of HER-2/neu-overexpressing or -amplified cancers was increased in both groups (34 and 32%, respectively). EGFR expression was more frequent in metastases (41%) than in primary tumours (16%). The proportions of cases with a basal phenotype were 26 and 30%, respectively. In paired primary tumours and metastases to the CNS, constancy of Her-2/neu status was observed in 87% of cases with only one sample turning Her-2/neu-negative and two samples acquiring overexpression/amplification in brain metastases. In contrast, steroid hormone receptors exhibited more frequently a loss of expression (17%) than a gain (9%) with 74% revealing a constant phenotype. We conclude that brain-metastasizing breast cancer belongs predominantly to the basal type or Her-2/neu type. Primary and metastatic tumours differ from each other only in a minority of cases, leading rather to a loss of steroid hormone receptors and to a gain of EGFR and Her-2/neu.

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“…27 In the current series, only one patient who received antibody therapy was included. In this case, no change of expression was observed.…”

Section: Discussionmentioning

confidence: 99%

“…In the majority of cases, the phenotype present in the intracerebral metastasis is already manifested in the primary tumour. Whether tumour patients with a risk profile for brain metastases should receive special surveillance to detect early and occult brain metastases 27 will have to be studied further.…”

Section: Discussionmentioning

confidence: 99%

Predominance of the basal type and HER-2/neu type in brain metastasis from breast cancer

et al. 2007

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“…Several studies demonstrated increased risk of brain relapse in breast cancer patients with overexpressed or amplified HER2-neu gene [5][6][7][8]. HER2 abnormalities occur in 20-30% of invasive breast cancers and are associated with more aggressive tumor growth, increased risk of relapse and shorter survival [9,10].…”

Section: Introductionmentioning

confidence: 99%

Risk factors for brain relapse in HER2-positive metastatic breast cancer patients

Duchnowska

Dziadziuszko

Czartoryska-Arłukowicz³

et al. 2009

Breast Cancer Res Treat

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“…12 This was unusual because CNS screening is not commonly conducted on asymptomatic patients. However, nearly 15% of the women screened had occult brain metastases, and Her-2 overexpression by the primary tumor was predictive of occult brain metastases.…”

Section: The Emerging Her-2 Connectionmentioning

confidence: 99%

“…Survival among patients with occult brain metastases was shorter than that of patients without CNS disease but was similar to the survival of patients with symptomatic brain metastases. 12 The causes of these trends are unknown. One theory suggests that Her-2 overexpression endows tumor cells with increased metastatic aggressiveness to sites such as the lungs and may similarly augment metastatic propensity to the CNS.…”

Section: The Emerging Her-2 Connectionmentioning

confidence: 99%

Breast Cancer Metastasis to the Central Nervous System

Weil

Palmieri

Bronder

et al. 2005

The American Journal of Pathology

389

322

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Clinically symptomatic metastases to the central nervous system (CNS) occur in Natural History of CNS MetastasisOf the nearly 1.3 million people diagnosed with cancer in the United States each year, ϳ100,000 to 170,000 will develop brain metastases, for an annual incidence of ϳ4.1 to 11.1 per 100,000 population (American Cancer Society Cancer Facts and Figures 2005, available at http://www.cancer.org). 1 Large autopsy studies suggest that between 20% and 40% of all patients with metastatic cancer will have brain metastases (http://www.cancer. org). [1][2][3][4] Given their overall greater frequency, lung and breast cancer are by far the most common tumors to present with brain metastases. 2,4 The incidence of symptomatic brain metastases among women with metastatic breast cancer ranges from 10 to 16%. 5 On average, the median latency between the initial diagnosis of breast cancer and the onset of brain metastasis is ϳ2 to 3 years. 1,2 In most cases, breast cancer patients develop brain metastases after metastases have appeared systemically in the lung, liver, and/or bone. 6 For the purposes of this review, central nervous system (CNS) and brain are used interchangeably.Several risk factors for brain metastases have been reported. Young age appears to correlate with elevated risk. 5,7 In a study of 1015 women with metastatic breast cancer, brain metastases occurred in 9% of women with estrogen receptor-negative (ERϪ) primary tumors, compared to 5% of patients with ERϩ primary tumors. 8 Many human breast cancers (25 to 33%) express Her-2, also known as the epidermal growth factor receptor erbB2 or the neu oncogene [Online Mendelian Inheritance in Man (OMIM) accession number 164870; http://www.ncbi. nlm.nih.gov/entrez/dispomim.cgi?id ϭ 164870, accessed 2.25.05]. Amplification or overexpression of Her-2 correlates with a shorter disease-free and overall survival time 9 and also appears to associate with a higher incidence of brain metastases. 10 -12 The metastasis of breast cancer to the CNS, either the brain parenchyma or the leptomeninges, is generally a late feature of metastatic disease. Metastases to the brain parenchyma are thought to be hematogenous in origin. In a retrospective survey of breast cancer patients with brain metastases, 78% had multiple intracerebral metastases, 14% had a solitary intracerebral metastasis, and the remaining 8% had leptomeningeal metastases. 7 Breast cancer is the most common solid tumor to exhibit leptomeningeal colonization. 13 Within the three membranous coverings, or meninges, that surround the brain, leptomeningeal metastases arise on the innermost covering (pia) and the middle membrane (arachnoid) or in the cerebral spinal fluid (CSF)-filled space between the arachnoid and the pia (subarachnoid space). 4 Spread to the leptomeninges may occur via multiple routes including hematogenous, direct extension, transport through

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Occult central nervous system involvement in patients with metastatic breast cancer: prevalence, predictive factors and impact on overall survival

Abstract: Patients with CNS involvement, whether occult or symptomatic, have an impaired survival. Occult CNS metastasis is relatively common, but impact on survival of treating occult CNS disease in patients with progressive systemic metastases is questionable.

Cited by 223 publications

References 19 publications

Predominance of the basal type and HER-2/neu type in brain metastasis from breast cancer

Predominance of the basal type and HER-2/neu type in brain metastasis from breast cancer

Risk factors for brain relapse in HER2-positive metastatic breast cancer patients

Breast Cancer Metastasis to the Central Nervous System

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