gms | German Medical Science

Objective: Estrogen receptor (ER), progesterone receptor (PgR), human EGF receptor 2 (Her2) and Ki-67 are important predictive and prognostic markers for making effective treatment decisions. Moreover, changes in these factors due to relapse are seen clinically, however, the frequency and clinical significance are still not fully understood. Most studies state that hormone receptors often change, while there are only few changes in Her2. Thus, changes in these markers and their correlations with prognosis were investigated.

Method: Out of 90 patients with breast cancer brain metastases in our tumor tissue bank from 2001 to 2012, there were 23 consecutive patients from whom both, the primary lesion and the brain metastasis were operated in our hospital. Patients with spinal metastases were excluded. The lesions were resected and ER, PgR, Her2 and Ki-67 were evaluated by immunostaining and molecular techniques including FISH. In addition, number and location of the brain metastases were evaluated. Moreover, samples from our tumor bank are currently being analyzed for novel biomarkers with regard to brain metastasis formation.

Results: The median age of the patient cohort was 56±9 years at first diagnosis. At that time 85% of the patients, who developed a brain metastasis later on already had lymph node involvement. 86% of the patients suffered from an invasive ductal, 10% from an invasive lobular carcinoma. The average time until the brain metastasis occurred was 34±6 months. The Ki-67 proliferation index increased significantly from a mean of 21% at the primary tumor site to 60% at relapse (p<0.001). Most patients developed one single brain metastasis at diagnosis (74%), but 26% had multiple brain metastases. The localisation of the metastases was mainly either the cerebellum (39%) or the fronto-temporal area (43.5%). The hormone receptor positive rate from the primary tumor to recurrence decreased from 43% to 17% and from 43% to 26% for ER and PgR, respectively. On the other hand, the rates of Her2+ tumors increased from 45% to 86%. 22% of all cases were triple negative.

Conclusions: ER and PgR decreased while Her2 and Ki-67 increased in cases of relapse. Interestingly, there was a doubling of Her2+ cases in the relapse situation. Therefore, we presently analyze different target genes to further understand this mechanism. These findings could become important for making effective treatment decisions and to screen affected patients more often, both neurologically and by MRI in order to diagnose brain lesions early.