Brain metastases in HER2-overexpressing metastatic breast cancer: Comparative analysis of trastuzumab levels in serum and cerebrospinal fluid

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 1525-1525 ◽  
Author(s):  
J. Stemmler ◽  
M. Schmitt ◽  
A. Willems ◽  
H. Bernhard ◽  
N. Harbeck ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Pilot Study ◽  
Serum Level ◽  
Metastatic Breast ◽  
Whole Brain Radiotherapy ◽  
Test System ◽  
Meningeal Carcinomatosis ◽  
Brain Radiotherapy ◽  
Increased Risk

1525 Purpose: Patients receiving trastuzumab for HER2-overexpressing MBC suffer from an increased risk to develop BM despite responsive visceral disease. The present pilot study was conducted to explore trastuzumab levels in S and CSF of MBC patients afflicted with BM, and to evaluate whether radiotherapy will lead to impairment the blood-brain barrier (BBB) to allow penetration of trastuzumab into CSF. Methods: Patients with BM from HER2-overexpressing MBC (IHC; DAKO Hercep Test) were included. Trastuzumab levels in S and CSF were determined at different time points by a newly developed immunoenzymatic test for functional, reactive trastuzumab. Results: Six out of 8 eligible patients were evaluable. Prior to whole-brain radiotherapy (WBRT), the median trastuzumab serum level was 52,054 ng/ml compared to a median CSF level of 124 ng/ml (ratio 420:1). After completion of WBRT, the median level of trastuzumab was 20,185 ng/ml in serum and 226 ng/ml in CSF (ratio 76:1). In two cases of concomitant meningeal carcinomatosis, the median serum level of trastuzumab after WBRT was 17,431 ng/ml and 356 ng/ml in CSF (ratio 49:1). Conclusion: These data indicate that the BBB prevent trastuzumab to reach adequate concentrations in CSF. These levels are increased under conditions of an impaired BBB, as is known for meningeal carcinomatosis and for patients receiving WBRT. The new test system in this pilot study provides the basis for the evaluation of radiotherapeutic strategies which allow most favorable penetration of trastuzumab into the CNS in patients receiving concomitant trastuzumab for HER2-overexpressing metastatic breast cancer. [Table: see text]

Clinical evidence for drug penetration of capecitabine and lapatinib uptake in resected brain metastases from women with metastatic breast cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 514-514 ◽  
Author(s):  
Aki Morikawa ◽  
David M. Peereboom ◽  
Quentin R Smith ◽  
Helen Thorsheim ◽  
Paul R Lockman ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Metastatic Breast ◽  
Whole Brain Radiotherapy ◽  
Clinical Activity ◽  
Brain Radiotherapy ◽  
Her2 Breast Cancer ◽  
Drug Concentrations ◽  
Cns Penetration ◽  
Preclinical Animal Models

514 Background: Brain metastasis (BM) is a challenging complication of metastatic breast cancer (MBC). Although systemic therapy is not commonly considered as a primary therapeutic approach, its potential in BM management has recently become apparent (Bachelot T et al Lancet Oncol 2013). Capecitabine and lapatinib in particular have been evaluated in HER2+ breast cancer BM (BCBM), but evidence for drug/metabolite CNS penetration is solely derived from preclinical animal models. In this study, we examined capecitabine, its metabolites, and lapatinib uptake in BCBMs resected due to medically indicated craniotomy. Methods: Study patients had BCBM requiring surgical resection. Patients with HER2-negative MBC received a single preoperative oral dose of capecitabine (1250mg/m2) 2-3 hrs before surgery. Those with HER2+ MBC received 2-3 oral doses of lapatinib (1250mg) daily, the last dose 2-3 hrs before surgery. On the day of surgery, serum was collected serially starting just before drug administration, intraoperatively, and through one hour after the conclusion of surgery. The concentration of capecitabine, its metabolites, and lapatinib from serum and BM were measured using liquid chromatography with tandem mass spectroscopy (LC-MS/MS). Results: 10 patients enrolled; PK data is available for 9: 6 for capecitabine and 3 for lapatinib. Capecitabine, its intermediate metabolites, 5FU, and lapatinib were detected in all BMs. Tumor capecitabine and 5-FU concentrations ranged from 3% to 129% and from 168% to 1422%, respectively, of serum concentrations. For lapatinib, the range was 21% to 700%. In a number of the BMs, drug concentrations were in the therapeutic range, whereas in others the concentrations were up to 10 fold lower. Conclusions: This is the first study to show capecitabine and lapatinib were detected in clinically relevant concentrations in a number of non-irradiated human BCBMs. This provides evidence for their ability to cross the blood-brain barrier, is consistent with prior published clinical activity, and supports further evaluation in a clinical setting prior to whole brain radiotherapy. Clinical trial information: NCT00795678.

scholarly journals Increased risk of SSEs in bone-only metastatic breast cancer patients treated with zoledronic acid

2017 ◽  
Vol 8 ◽  
pp. 18-22 ◽  
Author(s):  
Masashi Yanae ◽  
Shinichiro Fujimoto ◽  
Kaori Tane ◽  
Maki Tanioka ◽  
Kimiko Fujiwara ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Zoledronic Acid ◽  
Cancer Patients ◽  
Metastatic Breast ◽  
Breast Cancer Patients ◽  
Increased Risk

scholarly journals Risk of primary gastrointestinal cancers following incident non-metastatic breast cancer: a Danish population-based cohort study

2020 ◽  
Vol 7 (1) ◽  
pp. e000413
Author(s):  
Kasper Adelborg ◽  
Dóra Körmendiné Farkas ◽  
Jens Sundbøll ◽  
Lidia Schapira ◽  
Suzanne Tamang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Colon Cancer ◽  
Cohort Study ◽  
Metastatic Breast Cancer ◽  
Stomach Cancer ◽  
Metastatic Breast ◽  
Population Based ◽  
Gastrointestinal Cancers ◽  
Increased Risk

ObjectiveWe examined the risk of primary gastrointestinal cancers in women with breast cancer and compared this risk with that of the general population.DesignUsing population-based Danish registries, we conducted a cohort study of women with incident non-metastatic breast cancer (1990–2017). We computed cumulative cancer incidences and standardised incidence ratios (SIRs).ResultsAmong 84 972 patients with breast cancer, we observed 2340 gastrointestinal cancers. After 20 years of follow-up, the cumulative incidence of gastrointestinal cancers was 4%, driven mainly by colon cancers. Only risk of stomach cancer was continually increased beyond 1 year following breast cancer. The SIR for colon cancer was neutral during 2–5 years of follow-up and approximately 1.2-fold increased thereafter. For cancer of the oesophagus, the SIR was increased only during 6–10 years. There was a weak association with pancreas cancer beyond 10 years. Between 1990–2006 and 2007–2017, the 1–10 years SIR estimate decreased and reached unity for upper gastrointestinal cancers (oesophagus, stomach, and small intestine). For lower gastrointestinal cancers (colon, rectum, and anal canal), the SIR estimate was increased only after 2007. No temporal effects were observed for the remaining gastrointestinal cancers. Treatment effects were negligible.ConclusionBreast cancer survivors were at increased risk of oesophagus and stomach cancer, but only before 2007. The risk of colon cancer was increased, but only after 2007.

scholarly journals Sequential intra-arterial infusion of 90Y-resin microspheres and mitomycin C in chemo refractory liver metastatic breast cancer patients: a single centre pilot study

2020 ◽  
Vol 54 (1) ◽  
pp. 33-39
Author(s):  
Brigitte Maximiliana Aarts ◽  
Elisabeth Geneviève Klompenhouwer ◽  
Raphaëla Carmen Dresen ◽  
Christophe Michel Albert Louis Omer Deroose ◽  
Regina Gien Hoa Beets-Tan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Pilot Study ◽  
Mitomycin C ◽  
Progressive Disease ◽  
Metastatic Breast ◽  
Response To Treatment ◽  
Breast Cancer Patients ◽  
Arterial Infusion ◽  
Resin Microspheres

AbstractBackgroundThe aim of the study was to evaluate the safety and feasibility of intra-arterial mitomycin C (MMC) infusion after selective internal radiation therapy (SIRT) using Yttrium-90 (90Y) resin microspheres in liver metastatic breast cancer (LMBC) patients.Patients and methodsThe prospective pilot study included LMBC patients from 2012–2018. Patients first received infusion of 90Y resin microspheres, after 6–8 weeks response to treatment was assessed by MRI, 18F-FDG PET/CT and laboratory tests. After exclusion of progressive disease, MMC infusion was administrated 8 weeks later in different dose cohorts; A: 6 mg in 1 cycle, B: 12 mg in 2 cycles, C: 24 mg in 2 cycles and D: maximum of 72 mg in 6 cycles. In cohort D the response was evaluated after every 2 cycles and continued after exclusion of progressive disease. Adverse events (AE) were reported according to CTCAE version 5.0.ResultsSixteen patients received 90Y treatment. Four patients were excluded for MMC infusion, because of extra hepatic disease progression (n = 3) and clinical and biochemical instability (n = 1). That resulted in the following number of patient per cohort; A: 2, B: 1, C: 3 and D: 6. In 4 of the 12 patients (all cohort D) the maximum dose of MMC was adjusted due biochemical toxicities (n = 2) and progressive disease (n = 2). One grade 3 AE occurred after 90Y treatment consisting of a gastrointestinal ulcer whereby prolonged hospitalization was needed.ConclusionsSequential treatment of intra-arterial infusion of MMC after 90Y SIRT was feasible in 75% of the patients when MMC was administrated in different escalating dose cohorts. However, caution is needed to prevent reflux after 90Y SIRT in LMBC patients.

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