Regression of brain metastases from breast cancer with eribulin: a case report
© Matsuoka et al.; licensee BioMed Central Ltd. 2013
Received: 15 August 2013
Accepted: 13 December 2013
Published: 18 December 2013
Eribulin is a recently approved new therapeutic option for patients with metastatic breast cancer. According to several reports, eribulin has limited ability to cross the blood brain barrier. Recently, capecitabine and eribulin have been recognized as drugs with similar application for patients with advanced breast cancer. Although there have been several case reports describing the efficacy of capecitabine against brain metastases, no report of eribulin demonstrating efficacy for brain metastases exists today.
We describe a case of a 57-year-old Japanese woman who was diagnosed with breast cancer stage IV metastasized to multiple organs including liver and lung. After she received 3 regimens, she showed evidence of brain metastases, and whole brain radiation therapy was performed. Lapatinib and capecitabine was then administered as fourth-line chemotherapy, but the patient was hospitalized due to the exacerbation of interstitial pneumonitis and progression of brain and liver metastases. To control the systemic disease, eribulin was commenced as fifth-line chemotherapy. One month later, a significant response of brain metastases had been achieved, and this response has persisted for the last 4 months. We now describe a remarkable antitumor effect of eribulin against brain metastases from breast cancer. This case is the first report which indicates potential treatment of brain metastases using this medication.
This report suggests that eribulin treatment may be beneficial for breast cancer patients with brain metastases progressing after whole brain radiation therapy. However, further clinical studies are warranted to determine the clinical effect of eribulin in brain metastases.
KeywordsBreast cancer Blood brain barrier Eribulin Brain metastases P-glycoprotein
Eribulin is a recently approved new therapeutic option for patients with metastatic breast cancer . In a phase III study, patients with brain metastases were excluded unless these metastases had been previously treated and stabilized . Two phase II studies have excluded patients with active symptomatic brain metastases or progression of known brain metastases. However, the number of patients with brain metastases in these trials was not reported [3, 4]. It is therefore important to evaluate the efficacy and safety of eribulin in patients with brain metastases. In this case, our patient experienced regression of brain metastases from breast cancer with eribulin.
According to preclinical study, eribulin has limited ability to cross the blood brain barrier (BBB) [5–7]. Few macromolecules are transferred into the brain because vesicular transcytosis in the endothelial cells is considerably limited and the tight junction is located between the endothelial cells. In addition, there are several types of influx or efflux transporters at the BBB, such as P-glycoprotein (P-gp), multidrug resistance-associated protein, and breast cancer resistance protein [8, 9]. Permeability in the BBB is increased by WBRT. One study showed that radiation reduces P-gp expression in the brain . Therefore, it is likely that radiation allows eribulin to enter into brain tissue and exert a significant anti-tumor effect. However, the effect of a standard dose WBRT persists only for 4 weeks after radiation therapy (RT) , and attribution of the tumor regression to radiotherapy in the present case could be very limited since 8 months have passed after radiotherapy. On the other hand, brain metastases larger than 2 mm require angiogenesis for growth and therefore newly formed capillaries in brain metastases are fenestrated and they do not have a normal functioning blood brain barrier. Eribulin is known to be substrate for P-gp mediating drug efflux in BBB. But there is a decreased expression of P-gp in the neovasculature of brain metastases when compared to normal brain tissue [12–14]. This might explain the positive effects of eribulin on brain metastases.
There has been another reported case in which the treatment of brain metastases from breast cancer with eribulin in combination with WBRT was performed . The patient continued chemotherapy and received concomitant WBRT. After 3 cycles of eribulin mesylate, however, treatment was discontinued because of newly diagnosed liver metastases and progression in the lungs. Therefore, our case is the first report which shows a favorable effect on brain metastases. The treatment of eribulin was well tolerated without any high grade non-hematological toxicities, and the hematological toxicity was also acceptable.
Capecitabine and eribulin have been recognized as drugs with similar application for the patients with advanced breast cancer. Although there have been several case reports describing the efficacy of capecitabine against brain metastases from breast cancer, no report of eribulin demonstrating efficacy for brain metastases exists to date. Thus, the current case report is of value, and may help physicians determine which option to choose in treating patients with brain metastases.
This report suggests that eribulin treatment may be beneficial for breast cancer patients with brain metastases progressing after WBRT. However, further clinical studies are warranted to determine the clinical effect of eribulin in brain metastases.
Written informed consent was obtained from the patient for publication of this Case Report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
Hiromichi Matsuoka, MD: Oncologist, Psycho-Oncologist, Associate Professor of Department of Medical Oncology, Kinki University Faculty of Medicine, Osaka, Japan.
Interests: Chemotherapy of breast cancer, Palliative care, Psycho-Oncology.
Junji Tsurutani, MD: Oncologist, Associate Professor of Department of Medical Oncology, Kinki University Faculty of Medicine, Osaka, Japan.
Junko Tanizaki, MD: Oncologist, Associate Professor of Department of Medical Oncology, Kinki University Faculty of Medicine, Osaka, Japan.
Tsutomu Iwasa, MD: Oncologist, Associate Professor of Department of Medical Oncology, Kinki University Faculty of Medicine, Osaka, Japan.
Yoshifumi Komoike, MD: Surgeon, Proffesor of Department of Breast and Endocrine Surgery, Kinki University Faculty of Medicine, Osaka, Japan
Atsuko Koyama, MD: Psycho-Oncologist, Professor of Department of Medical Oncology, Division of Psychosomatic Medicine, Kinki University Faculty of Medicine, Osaka, Japan.
Kazuhiko Nakagawa, MD: Oncologist, Professor of Department of Medical Oncology, Kinki University Faculty of Medicine, Osaka, Japan.
Human epidermal growth factor receptor 2
Fluorescent in situ hybridization
Whole brain radiation therapy
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