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

Abstract

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.

Treatment and pattern of bone metastases in 1094 patients with advanced breast cancer – Results from the prospective German Tumour Registry Breast Cancer cohort study

“…Taken together, 35% of the whole cohort reported boneonly metastasis at the start of treatment, which is consistent with the literature naming a proportion of 17e37% [11,24]. In contrast, HER2-positive tumours are more likely to metastasise to the brain during the course of disease, with an incidence of 25e34% [2,25,26]. Consistent with these results, the frequency of brain metastases in the HER2-positive setting was 31% during the course of disease in our cohort (data on file).…”

Pathology of hereditary breast cancer

“…Conversely, the BRCA1 pathway seems to be altered in sporadic breast cancers with a 'basal' phenotype. 38 The trend of basal-like cancers to metastasise to brain, 39,40 which was also shown in patients with BRCA1 mutations, is also noteworthy. 41 Can pathology aid clinical decision making?…”

Patho-biological aspects of basal-like breast cancer

“…CNS or brain metastases traditionally occur in 10-16% of metastatic breast cancer patients and are associated with a dismal prognosis. In a recent study, Gaedcke et al [115] found that the majority of breast cancer that developed CNS metastases are BLC and HER2 positive. These CNS metastatic tumours are usually hormone receptor negative, EGFR and basal CKs (CK5/14) positive [116,117].…”