FOR THOSE WITH BRAIN METS, making treatment decisions

[Lani]

some useful information:

Anticancer Drugs. 2007 Jan;18(1):23-8. Links
Ratio of trastuzumab levels in serum and cerebrospinal fluid is altered in HER2-positive breast cancer patients with brain metastases and impairment of blood-brain barrier.

Stemmler HJ, Schmitt M, Willems A, Bernhard H, Harbeck N, Heinemann V.
Medical Department III, Ludwig-Maximilians University of Munich, Clinic Grosshadern, Munich, Germany. Joachim.Stemmler@med.uni-muenchen.de
Patients receiving trastuzumab for HER2-overexpressing metastatic breast cancer seem to suffer from an increased risk of brain metastases, even in cases with responsive disease. To evaluate whether trastuzumab is able to penetrate the blood-brain barrier, we measured trastuzumab levels in the serum and in cerebrospinal fluid of metastatic breast cancer patients with brain metastases receiving trastuzumab for HER2-overexpressing metastatic breast cancer. In a pilot study, metastatic breast cancer patients with brain metastases and HER2-overexpressing tumors (HercepTest; Dako, Copenhagen, Denmark) were included. At different time points, trastuzumab levels in the serum and cerebrospinal fluid were measured using a newly developed immunoenzymatic test for trastuzumab. Six out of eight patients were evaluable for determination of trastuzumab level in the serum and cerebrospinal fluid. Before radiotherapy, median trastuzumab level in the serum was 52 054 ng/ml compared with 124 ng/ml in cerebrospinal fluid (ratio 420 : 1). After completion of radiotherapy, median trastuzumab level was 20 185 ng/ml in the serum and 226 ng/ml in cerebrospinal fluid, respectively (ratio 76 : 1). With concomitant meningeal carcinomatosis, trastuzumab level in the serum after radiotherapy was 17 431 and 356 ng/ml in cerebrospinal fluid (ratio 49 : 1). For the first time, we present clinical evidence that trastuzumab levels in cerebrospinal fluid are increased under conditions of an impaired blood-brain barrier such as meningeal carcinomatosis or radiotherapy. This evidence supports the concept of continuing trastuzumab therapy in patients with brain metastases treated by radiotherapy. Monitoring of trastuzumab levels in the serum and cerebrospinal fluid may enable individualized therapy strategies in metastatic breast cancer patients with brain metastases, and lead to a better understanding of trastuzumab pharmacokinetics in the cerebrospinal fluid and serum.
PMID: 17159499 [PubMed - indexed for MEDLINE]

[Jean]

Lani,
I am curious, have you read any articles about spread of diseas to brain
without being stage 2,3,or 4? Interesting thing my onc said while in SA
that most brain mets occurs in later stage of disease and now I am wondering if there is any documentation on earlier stage.

Thanks in advance,
Jean

[StephN]

I would be curious as to what KINDS of radiotherapy those patients had.

This study had been theorized by my med onc a while back. After my brain mets he said it was important to stay on Herceptin as it was possible some was entering my blood brain barrier, but at that time they had no way to measure it.

He strongly suggested that the two mets I had were seeded either before I started Herceptin or shortly after I began treatment for my wild liver mets, and that I may not have any more brain mets after those two were treated with gamma knife. So far no more have appeared.

[Lani]

10-15% was listed as risk of brain mets as site of first recurrence(if I recall right, and I may not at the moment!) As more her2+ patients are treated with herceptin the incidence of brain mets as site of first recurrence is increasing!

When ALL breast cancer is lumped together (my pet peave) the following results were posted by me in May of 2006:

ABSTRACT: Identifying breast cancer patients at risk for Central Nervous System (CNS) metastases in trials of the International Breast Cancer Study Group (IBCSG) [Annals of Oncology; Subscribe; Sample]
Background: We sought to determine whether a high-risk group could be defined among patients with operable breast cancer in whom a search of occult central nervous system (CNS) metastases was justified.

Patients and methods: We evaluated data from 9524 women with early breast cancer (42% node-negative) who were randomized in International Breast Cancer Study Group clinical trials between 1978 and 1999, and treated without anthracyclines, taxanes, or trastuzumab. We identified patients whose site of first event was CNS and those who had a CNS event at any time.

Results: Median follow-up was 13 years. The 10-year incidence (10-yr) of CNS relapse was 5.2% (1.3% as first recurrence). Factors predictive of CNS as first recurrence included: node-positive disease (10-yr = 2.2% for > 3 N+), estrogen receptor-negative (2.3%), tumor size > 2 cm (1.7%), tumor grade 3 (2.0%), < 35 years old (2.2%), HER2-positive (2.7%), and estrogen receptor-negative and node-positive (2.6%). The risk of subsequent CNS recurrence was elevated in patients experiencing lung metastases (10-yr = 16.4%).

Conclusion: Based on this large cohort we were able to define risk factors for CNS metastases, but could not define a group at sufficient risk to justify routine screening for occult CNS metastases.


I have posted at least 3 other studies over the years with stats on this.

Sorry I don't have the time at the moment to search them out. Try to remind me later!