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. The patient complained of headache and tinnitus but there were no neurologic symptoms. Magnetic resonance imaging (MRI) of her brain showed two metastatic lesions with edema at the cerebrum; the larger lesion measured 2.7×2.1 cm (Figure 1A).

Five years earlier, in July 2008, the patient had undergone a left modified radical mastectomy for invasive ductal carcinoma. The pathologic stage of the disease was T3N3M0 and the histologic grade was low. 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/m² and cyclophosphamide 600 mg/m², every 3 weeks, intravenously for four cycles; followed by paclitaxel 175 mg/m², every 3 weeks, intravenously for four cycles). Following the chemotherapy treatment, she received radiation therapy and tamoxifen.

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/m², every 3 weeks, intravenously) plus capecitabine (1,250 mg/m² bis in die, per os [p.o.], on days 1–14, 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 γ-knife SRT and received CMF (cyclophosphamide 100 mg/m² p.o., on days 1–14, methotrexate 40 mg/m² intravenously on days 1 and 8, and 5-fluorouracil 600 mg/m² 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/m² 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. The MBT progressed systemically 12 months after eribulin single therapy in November 2014.

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/m², every 3 weeks, intravenously) and doxorubicin (50 mg/m², every 3 weeks, intravenously) was administered from May 2012 to August 2012. Salvage mastectomy for wound management was performed in September 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/m², 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/m², on days 1–14, every 3 weeks, p.o.) as third-line chemotherapy. A partial response was achieved.

Despite this partial response, brain metastasis developed after 20 cycles of lapatinib and capecitabine. 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/m², 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).