brain metastasis from breast cancer is less common than metastasis to the bone , lung , and liver . however , the prognosis of brain metastasis is very poor , with a median survival time ranging between 5.4 and 13 months . additionally , it is usually discovered at a later stage during the systemic progression of breast cancer . while brain metastasis is generally observed in 10% to 20% of patients with metastatic breast cancers ( mbc ) , autopsy series have revealed that it is , in fact , present in > 34% of patients . current therapies for brain metastasis include whole brain radiotherapy ( wbrt ) , surgery , stereotactic radiation therapy ( srt ) , corticosteroids , and systemic chemotherapy . wbrt is considered the standard treatment for metastatic brain tumors ( mbt ) ; the role of chemotherapy is still controversial owing to the difficulties associated with passage through the blood - brain barrier ( bbb ) . eribulin is a microtubule dynamic inhibitor synthesized from halichondrin b , a natural marine product . however , unlike other tubulin polymerization inhibitors , halichondrin b does not function by inhibiting tubulin growth or by shortening the microtubule . eribulin is currently acknowledged as a new line of therapy for mbc . in a phase iii study ( eribulin monotherapy versus treatment of physician 's choice in patients with mbc [ embrace ] ) , eribulin treatment improved overall survival in patients with heavily pretreated mbc , but these studies included few patients with brain metastases . therefore , it is crucial to evaluate the effectiveness and safety of eribulin in the treatment of patients with breast cancer with brain metastasis . herein , we report two cases of breast cancer with brain metastasis that were treated with eribulin mesylate combined with local treatment for mbt . mbt were found during first - line palliative chemotherapy ( docetaxel plus capecitabine ) in a 43-year - old woman with breast cancer with metastasis to the lung and the mediastinal nodes , in inje university busan paik hospital in june 2013 . magnetic resonance imaging ( mri ) of her brain showed two metastatic lesions with edema at the cerebrum ; the larger lesion measured 2.72.1 cm ( figure 1a ) . five years earlier , in july 2008 , the patient had undergone a left modified radical mastectomy for invasive ductal carcinoma . the genetic subtype was luminal b - like human epidermal growth factor receptor 2 ( her2)-negative , which was positive for estrogen receptor ( er ) and progesterone receptor ( pr ) , negative for her2 , and the ki-67 labeling index > 14% . the patient received adjuvant chemotherapy with doxorubicin and cyclophosphamide followed by paclitaxel ( doxorubicin 60 mg / m and cyclophosphamide 600 mg / m , every 3 weeks , intravenously for four cycles ; followed by paclitaxel 175 mg / m , every 3 weeks , intravenously for four cycles ) . following the chemotherapy treatment , four years after the surgery , in may 2012 , positron emission tomography ( pet ) revealed metastases in the patient 's right lung , and in her paratracheal , subcarinal , and right supraclavicular lymph nodes , although she showed no symptoms or signs of either local or distant metastatic recurrence . a needle biopsy confirmed the presence of metastatic lesions from breast cancer in the right supraclavicular lymph node . the genetic subtype of the metastatic node was luminal b - like her2-negative ( er - positive , pr - negative , her2-negative , and ki-67 labeling index > 14% ) . based on the first - line palliative chemotherapy , the patient received docetaxel ( 75 mg / m , every 3 weeks , intravenously ) plus capecitabine ( 1,250 mg / m bis in die , per os [ p.o . ] , on days 114 , with a 1-week withdrawal period , every 3 weeks ) for 15 cycles . the mbt were detected during the docetaxel plus capecitabine chemotherapy in june 2013 ( figure 1a ) . the patient underwent -knife srt and received cmf ( cyclophosphamide 100 mg / m p.o . , on days 114 , methotrexate 40 mg / m intravenously on days 1 and 8 , and 5-fluorouracil 600 mg / m intravenously on days 1 and 8 , every 4 weeks ) for four cycles as second - line palliative chemotherapy . the 4-month follow - up brain mri showed that the metastatic lesion had decreased in size from 2.7 to 2.5 cm ( figure 1b ) , but the pet - computed tomography ( ct ) image showed increased glucose uptake and size in the metastatic lymph nodes of the mediastinum , indicating aggravation . the patient received wbrt ( total 3,000 cgy : 300 cgy / day for 10 days ) . she then received eribulin single therapy ( 1.4 g / m on days 1 and 8 , intravenously , every 3 weeks ) 4 days later as third - line palliative chemotherapy in november 2013 . at the 3-month follow - up appointment , after the fourth cycle of eribulin , the mbt had further decreased in size ; the heterogeneous enhancing lesion decreased from 2.5 to 1.7 cm . additionally , the oval - shaped cystic lesion had decreased from 1.5 to 0.8 cm ( figure 2a ) . after the sixth cycle of eribulin treatment , the patient discontinued use owing to financial reasons ; the eribulin therapy was restarted 3 months later . at the 8-month follow - up examination in july 2014 , after the eighth cycle of eribulin treatment , the mbt showed regression with systematically stable disease ( figure 2b ) . the patient was still receiving eribulin and there were no severe hematologic or non - hematologic adverse events reported during or after the chemotherapy . at the 10-month follow - up examination in september 2014 , following the tenth cycle of eribulin treatment , a pet - ct scan showed that the mediastinal nodes had increased in size and that glucose metabolism in these nodes had also increased . as the patient had the luminal b breast cancer subtype , and she was postmenopausal , we initiated treatment with an aromatase inhibitor ( letrozole ) in december 2014 . in july 2015 , we changed the regimen to everolimus plus exemestane due to systemic progression . the patient is still alive , without any neurologic symptoms , more than 24 months following the mbt diagnosis . in may 2012 , a 47-year - old woman visited the breast cancer center of gangnam severance hospital for evaluation of an ulcerofungating mass involving her right whole breast . she was diagnosed with stage iv invasive ductal carcinoma ( ct4n3m1 ) , which had metastasized to distant organs including the liver and bone . pathological examination via immunohistochemistry showed that the tumor was er- and pr - negative , and her2-positive . primary systemic chemotherapy , consisting of six cycles of docetaxel ( 75 mg / m , every 3 weeks , intravenously ) and doxorubicin ( 50 mg / m , every 3 weeks , intravenously ) was administered from may 2012 to august 2012 . two months after completion of the first - line treatment , a follow - up liver ct showed progression of the hepatic metastasis with increased tumor number and size . as a second - line systemic treatment , paclitaxel ( 75 mg / m , every 3 weeks , intravenously ) and trastuzumab ( 8 mg / kg loading dose and 6 mg / kg , every 3 weeks , intravenously ) were administered . in may 2013 , a liver ct revealed that the metastatic lesions in the liver had progressed despite the six cycles of paclitaxel and trastuzumab . the patient was treated with lapatinib ( 1,250 mg , daily , p.o . ) and capecitabine ( 2,000 mg / m , on days 114 , every 3 weeks , p.o . ) as third - line chemotherapy . on july 20 , 2014 , the patient visited the emergency department with right - sided weakness . a brain mri identified a 2.5-cm metastatic lesion on her left frontal - parietal lobe ( figure 3a ) . craniotomy and surgical resection of the tumor was successfully performed on july 21 , 2014 . at the time of the brain metastasis , a newly developed lesion was found in the s8 area of the liver on ct performed on july 29 , 2014 . after tumor removal , systemic therapy with eribulin ( 1.4 g / m , on days 1 and 8 , every 3 weeks , intravenously ) was started in august 2014 . for further local treatment of the brain metastasis , the patient received wbrt ( total 3,000 cgy : 250 cgy / day for 12 days ) with a boost dose to the tumor bed ( total 3,600 cgy : 300 cgy / day for 12 days ) . during the treatment period with eribulin , local wound dehiscence developed at the site of craniotomy in the scalp . to manage this , a local skin flap surgery was performed , and the eribulin treatment was temporally halted for 4 weeks . as of december 2015 , the patient was on her 23rd cycle of eribulin , without tumor recurrence or progression in the brain or liver . her last follow - up studies , including brain mri and liver ct , carried out on november 20 , 2015 revealed stable disease ( figure 3b ) . mbt were found during first - line palliative chemotherapy ( docetaxel plus capecitabine ) in a 43-year - old woman with breast cancer with metastasis to the lung and the mediastinal nodes , in inje university busan paik hospital in june 2013 . magnetic resonance imaging ( mri ) of her brain showed two metastatic lesions with edema at the cerebrum ; the larger lesion measured 2.72.1 cm ( figure 1a ) . five years earlier , in july 2008 , the patient had undergone a left modified radical mastectomy for invasive ductal carcinoma . the genetic subtype was luminal b - like human epidermal growth factor receptor 2 ( her2)-negative , which was positive for estrogen receptor ( er ) and progesterone receptor ( pr ) , negative for her2 , and the ki-67 labeling index > 14% . the patient received adjuvant chemotherapy with doxorubicin and cyclophosphamide followed by paclitaxel ( doxorubicin 60 mg / m and cyclophosphamide 600 mg / m , every 3 weeks , intravenously for four cycles ; followed by paclitaxel 175 mg / m , every 3 weeks , intravenously for four cycles ) . following the chemotherapy treatment , four years after the surgery , in may 2012 , positron emission tomography ( pet ) revealed metastases in the patient 's right lung , and in her paratracheal , subcarinal , and right supraclavicular lymph nodes , although she showed no symptoms or signs of either local or distant metastatic recurrence . a needle biopsy confirmed the presence of metastatic lesions from breast cancer in the right supraclavicular lymph node . the genetic subtype of the metastatic node was luminal b - like her2-negative ( er - positive , pr - negative , her2-negative , and ki-67 labeling index > 14% ) . based on the first - line palliative chemotherapy , the patient received docetaxel ( 75 mg / m , every 3 weeks , intravenously ) plus capecitabine ( 1,250 mg / m bis in die , per os [ p.o . ] , on days 114 , with a 1-week withdrawal period , every 3 weeks ) for 15 cycles . the mbt were detected during the docetaxel plus capecitabine chemotherapy in june 2013 ( figure 1a ) . the patient underwent -knife srt and received cmf ( cyclophosphamide 100 mg / m p.o . , on days 114 , methotrexate 40 mg / m intravenously on days 1 and 8 , and 5-fluorouracil 600 mg / m intravenously on days 1 and 8 , every 4 weeks ) for four cycles as second - line palliative chemotherapy . the 4-month follow - up brain mri showed that the metastatic lesion had decreased in size from 2.7 to 2.5 cm ( figure 1b ) , but the pet - computed tomography ( ct ) image showed increased glucose uptake and size in the metastatic lymph nodes of the mediastinum , indicating aggravation . the patient received wbrt ( total 3,000 cgy : 300 cgy / day for 10 days ) . she then received eribulin single therapy ( 1.4 g / m on days 1 and 8 , intravenously , every 3 weeks ) 4 days later as third - line palliative chemotherapy in november 2013 . at the 3-month follow - up appointment , after the fourth cycle of eribulin , the mbt had further decreased in size ; the heterogeneous enhancing lesion decreased from 2.5 to 1.7 cm . additionally , the oval - shaped cystic lesion had decreased from 1.5 to 0.8 cm ( figure 2a ) . after the sixth cycle of eribulin treatment , the patient discontinued use owing to financial reasons ; the eribulin therapy was restarted 3 months later . at the 8-month follow - up examination in july 2014 , after the eighth cycle of eribulin treatment , the mbt showed regression with systematically stable disease ( figure 2b ) . the patient was still receiving eribulin and there were no severe hematologic or non - hematologic adverse events reported during or after the chemotherapy . at the 10-month follow - up examination in september 2014 , following the tenth cycle of eribulin treatment , a pet - ct scan showed that the mediastinal nodes had increased in size and that glucose metabolism in these nodes had also increased . as the patient had the luminal b breast cancer subtype , and she was postmenopausal , we initiated treatment with an aromatase inhibitor ( letrozole ) in december 2014 . in july 2015 , we changed the regimen to everolimus plus exemestane due to systemic progression . the patient is still alive , without any neurologic symptoms , more than 24 months following the mbt diagnosis . in may 2012 , a 47-year - old woman visited the breast cancer center of gangnam severance hospital for evaluation of an ulcerofungating mass involving her right whole breast . she was diagnosed with stage iv invasive ductal carcinoma ( ct4n3m1 ) , which had metastasized to distant organs including the liver and bone . pathological examination via immunohistochemistry showed that the tumor was er- and pr - negative , and her2-positive . primary systemic chemotherapy , consisting of six cycles of docetaxel ( 75 mg / m , every 3 weeks , intravenously ) and doxorubicin ( 50 mg / m , every 3 weeks , intravenously ) was administered from may 2012 to august 2012 . two months after completion of the first - line treatment , a follow - up liver ct showed progression of the hepatic metastasis with increased tumor number and size . as a second - line systemic treatment , paclitaxel ( 75 mg / m , every 3 weeks , intravenously ) and trastuzumab ( 8 mg / kg loading dose and 6 mg / kg , every 3 weeks , intravenously ) were administered . in may 2013 , a liver ct revealed that the metastatic lesions in the liver had progressed despite the six cycles of paclitaxel and trastuzumab . the patient was treated with lapatinib ( 1,250 mg , daily , p.o . ) and capecitabine ( 2,000 mg / m , on days 114 , every 3 weeks , p.o . ) as third - line chemotherapy . on july 20 , 2014 , the patient visited the emergency department with right - sided weakness . a brain mri identified a 2.5-cm metastatic lesion on her left frontal - parietal lobe ( figure 3a ) . craniotomy and surgical resection of the tumor was successfully performed on july 21 , 2014 . at the time of the brain metastasis , a newly developed lesion was found in the s8 area of the liver on ct performed on july 29 , 2014 . after tumor removal , systemic therapy with eribulin ( 1.4 g / m , on days 1 and 8 , every 3 weeks , intravenously ) was started in august 2014 . for further local treatment of the brain metastasis , the patient received wbrt ( total 3,000 cgy : 250 cgy / day for 12 days ) with a boost dose to the tumor bed ( total 3,600 cgy : 300 cgy / day for 12 days ) . during the treatment period with eribulin , local wound dehiscence developed at the site of craniotomy in the scalp . to manage this , a local skin flap surgery was performed , and the eribulin treatment was temporally halted for 4 weeks . as of december 2015 , the patient was on her 23rd cycle of eribulin , without tumor recurrence or progression in the brain or liver . her last follow - up studies , including brain mri and liver ct , carried out on november 20 , 2015 revealed stable disease ( figure 3b ) . the clinical regression , without symptoms , of mbt from breast cancer was sustained for 24 and 18 months in case 1 and case 2 , respectively , using multimodality therapies that included surgery , srt , wbrt , chemotherapy , and endocrine therapy . wbrt followed by eribulin induced a continuous decrease in the size of the mbt with systemic disease stability for 12 months in case 1 . surgery followed by eribulin with concurrent wbrt inhibited systemic progression for 18 months in case 2 . in order to effectively treat mbt , a chemotherapeutic agent should induce effective cytotoxicity in the tumor cells . it should be able to reach adequate concentrations , maintain this concentration in the tumor 's extracellular space , and cross the bbb while evading active efflux mechanisms . compared with that of primary brain tumors , the bbb of mbt tends to be relatively permeable . in addition , the expression of p - glycoprotein ( p - gp ) , which is associated with permeability of the bbb , is decreased in mbt . furthermore , the permeability of the bbb can be increased by wbrt . in line with our experience , a previous case report showed that eribulin therapy may be beneficial in the treatment of mbt arising from breast cancer . in a patient with progression of brain and liver metastasis after wbrt followed by lapatinib and capecitabine treatment , eribulin achieved a significant response in the mbt 1 month later and this effect lasted for 4 months . the following hypotheses could explain the mechanism of the therapeutic effect of eribulin on mbt in our cases : first , eribulin was efficacious against the systemic disease ; second , wbrt may have facilitated the passage of eribulin across the bbb by decreasing the function of p - gp ; third , the antiangiogenic action of eribulin could have increased the transmission of eribulin itself . a new mode of action for eribulin that involves remodeling of the tumor vasculature through a novel antivascular activity has already been reported . eribulin may offer a clinical benefit in the treatment of mbt arising from breast cancer . wbrt followed by eribulin , or eribulin with concurrent wbrt may represent an effective treatment option for breast cancer patients with brain metastasis . future studies are warranted to evaluate the precise effect of eribulin and its mechanism of action on brain metastasis .
the prognosis associated with brain metastasis arising from breast cancer is very poor . 
 eribulin is a microtubule dynamic inhibitor synthesized from halichondrin b , a natural marine product . in a phase iii study ( embrace ) , eribulin improved overall survival in patients with heavily pretreated metastatic breast cancers . 
 however , these studies included few patients with brain metastases . 
 metastatic brain tumors ( mbt ) were detected during first - line palliative chemotherapy in a 43-year - old woman with breast cancer metastasis to the lung and mediastinal nodes ; the genetic subtype was luminal b - like human epidermal growth factor receptor 2 ( her2)-negative . whole brain radiotherapy ( wbrt ) followed by eribulin treatment continuously decreased the size , and induced regression , of the mbt with systemic disease stability for 12 months . another 48-year - old woman with metastatic breast cancer ( her2 + subtype ) presented with mbt . following surgical resection of the tumor , eribulin with concurrent wbrt showed regression of the mbt without systemic progression for 18 months .