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We report the case of a 46-year-old Japanese woman diagnosed with Stage Ⅳ right breast cancer, cT1cN1M1(ovarian and peritoneal metastases). We administered bevacizumab+paclitaxel as the first-line treatment. In the 13th course, the peritoneal dissemination progressed, and the regimen was changed to eribulin(1.4 mg/m2)as the second-line treatment. During the second course, abdominal distension developed and was resolved during follow-up. However, abdominal distension and pain were observed from day 9 of the fourth course. Based on the results of blood chemistry and CT scans, she was diagnosed with acute pancreatitis(CT Grade 1)and was admitted to the hospital. After fasting and fluid replacement therapy, her clinical symptoms and laboratory data improved, and was discharged from the hospital 8 days later. She had no history of excessive alcohol consumption and no evidence of biliary disease, and was considered having eribulin-induced pancreatitis.

Pseudocirrhosis, which is radiologically and clinically similar to liver cirrhosis, may develop following chemotherapy for breast cancer with liver metastasis. There are few reports of eribulin treatment. We report 5 patients with metastatic or recurrent breast cancer who developed pseudocirrhosis during eribulin treatment. All patients had diffuse liver metastasis, and the liver metastases significantly reduced in size during the early phase of eribulin treatment, when they developed pseudocirrhosis. Subsequently, the patients had poor prognoses.

In the treatment of advanced breast cancer, onlya few drugs confer overall survival(OS)benefit. Eribulin is a drug that was shown to extend OS in an international phase Ⅲtrial; however, the underlying mechanism is thought to involve cancer microenvironment regulation. The concept of "breast cancer subtype discordance" implies the biological changes that accompany treatment. Herein, we encountered a case of advanced breast cancer in a 54-year-old woman that showed biological changes after eribulin chemotherapy. The patient noticed a lump in her left breast and visited a nearby doctor, who referred her to our hospital for close examination and treatment. Ultrasonographyrevealed a large mass at the center of the left mammarygland and axillaryly mph node swelling. Core-needle biopsyconfirmed an invasive ductal carcinoma(ER stronglypositive, PgRnegative, HER-2 negative, Ki-67 low expression). CT findings showed multiple lung metastases. Letrozole was administered for cT4N2M1, stage Ⅳ, Luminal A, which showed progression to the left side with advances in breast cancer. Six months later, the primarytumor and axillaryly mph nodes showed progression. Subsequent treatment with eribulin was started, and partial response was obtained; however, new lymph node metastasis developed in the axilla after 11 cycles. The primary tumor and axillaryly mph nodes showed stronglypositive ER expression, were PgR-negative and HER2-positive, and showed Ki-67 low expression and HER2-positive conversion.

Background: The neutrophil lymphocyte ratio is reported to be a poor prognostic factor in each carcinoma, and the possibility of predicting the therapeutic effect of chemotherapy, for example, is being studied. In this study, we measured the NLR before and after administration of eribulin and the NLR before and after the final administration in breast cancer patients and examined the relationship with the therapeutic effect., Methods: Eleven primary breast cancer patients were examined after eribulin was administered; PD was confirmed eventually, and administration was discontinued. The NLR was determined before the first administration of eribulin and 7 days after the administration; the NLR before the final administration and after the last administration were each tested with p<0.05 as the significance level and using the t test., Results: The average value of NLR before initial administration was 4.07±2.11, and the average value after 7 days of administration was 2.47±1.97. The NLR before initial administration tended to be higher, and a significant difference was observed(p<0.05). The average NLR value before the final administration was 4.02±2.04, and the average value of the NLR after the final administration was 3.19 ±1.76, showing no significant difference(p=0.27, NS).

A 65-year-old woman underwent mastectomy and dissection of a level I axillary lymph node in January 2002 for left breast cancer. The diagnosis was T1N0M0 scirrhous carcinoma that was estrogen receptor-positive, progesterone receptorpositive, and human epidermal growth factor receptor 2-negative. After 3 years 10 months, during which the patient underwent adjuvant therapy with oral aromatase inhibitors, she developed bilateral multiple lung metastases. These were treated with the anticancer agents anthracycline and taxane. Progressive disease(more and larger lung metastases)was diagnosed in April 2013, and bevacizumab plus paclitaxel combination therapy was started. After completion of 4 courses, a lung abscess appeared, which was conjectured to represent rapid tumor necrosis that had become infected. As several tumors remained solid even after the lung abscess improved, the patient received 18 courses of eribulin monotherapy. Computed tomography in April 2016 revealed only patches of linear or cord-like scarring in both lungs, with no metastatic or recurrent foci. In this case, a patient with recurrent breast cancer responded to the sequential administration of bevacizumab plus paclitaxel combination therapy followed by eribulin monotherapy.

Eribulin is evaluated as the only agent that can extend the survival time of patients with advanced or recurrent breast cancer, when used as or after third-line chemotherapy. We retrospectively analyzed the efficacy of eribulin for the treatment of advanced or recurrent breast cancer in our hospital, considering the relative dose intensity(RDI), time to treatment failure (TTF), pretreatment regimen number, and tumor subtype. Of the 36 patients who were treated with eribulin between December 2011 and August 2016, we studied 31 patients who received eribulin as a single agent. The median RDI was 0.75 (range: 0.44-1). The response rate was 22.5%, the disease control rate was 80.6%, and the clinical benefit rate was 45.2%. Overall survival(OS)was not associated with the RDI, previous regimen number, or tumor subtype; however, OS was affected by the TTF. Eribulin is a novel drug that has a different mechanism of action compared with those of conventional anticancer drugs. Therefore, prolonging the duration of eribulin administration may be more important than maintaining the RDI.

A 79-year-old woman presented with a chief complaint of a palpated tumor on her right axilla. The right breast tumor size was 18mm and the axillary lymph node size was 30 mm, as detected with ultrasonography. Pathological findings indicated the presence of an ER(-), Pg R(-), HER2-negative apocrine carcinoma. The presence of axillary lymph node metastasis was diagnosed from the apocrine carcinoma. Eribulin(1.5mg)was administered 3 times before surgery. Tumors were significantly reduced. The Bt+Ax(Patey procedure)dissection was performed until Level 2. The pathological findings of the tumor revealed coagulation, necrosis, and the remaininglimited cancer lesions in the periphery zone. No remainingcancer cells were detected in the lymph nodes. The breast apocrine carcinoma was determined as a special type of invasive cancer. Although the prognosis is positive, the current case was considered highly malignant with a 50% positive Ki-67 rating. Although eribulin was effective, it seems that this case requires strict follow-up observations.

Patients and Methods: This retrospective observational study contains advanced or metastatic breast cancer female patients who pretreated with anthracycline and/or taxane received eribulin(ERI)mesylate. The primary endpoint was the progressionfree survival(PFS)and secondary endopoints were objective response rate(ORR), clinical benefit rate(CBR), overall survival (OS), and post-progression survival(PPS)., Results: A total of 32 patients underwent chemotherapy cycles(median 3; range 1-9 cycles). The ORR was 15.6% and the CBR was 31.3%. The median PFS, OS and PPS were 2.9 months, 8.5 months, 5.6 months respectively. The OS, PPS for relative dose intensity(RDI)<85% and RDI≥85% were 7.2 months, 3.4 months and 14.5 months, 11.4 months, respectively(p=0.005, 0.004). In multivariate analysis for OS and PPS, the visceral disease, total dose of ERI and RDI correlated with OS and PPS. The most frequent treatment-related Grade 3/4 adverse events was neutropenia( 56%). No Grade 3 and 4 peripheral sensory neuropathy was occurred., Conclusions: ERI exhibited efficacy and tolera- bility in patients with heavily pretreated A/MBC. The total dose and RDI of ERI would induce favorable effect for prognosis.

We experienced 2 cases in which eribulin mesylate was effective for taxane-resistant advanced breast cancer. Case 1: A 65- year-old woman was diagnosed with advanced breast cancer(T4cN2aM0, stage III B)and treated with chemotherapy(nabpaclitaxel). Bone metastasis was observed; then, she sequentially received epirubicin and cyclophosphamide, nab-paclitaxel, and bevacizumab and paclitaxel. However, lung metastases appeared, and we changed the regimen to eribulin mesylate. We administered 11 courses of eribulin mesylate before bone marrow metastasis appeared. Eribulin mesylate was effective for more than 1 year. Case 2: A 77-year-old woman was diagnosed with advanced breast cancer(T4bN3cM1, stage IV), and liver and pleural metastasis were observed during an examination at the first visit. Four courses of nab-paclitaxel were administered, but because of the increase in pleural effusion, we changed the regimen to eribulin mesylate. Thirteen courses of eribulin mesylate were administered before the disease progressed. The progression-free survival was 9.53 months. Through the 2 cases in which eribulin mesylate was effective for taxane-resistant advanced breast cancer, the effect of eribulin mesylate compared to taxane was clinically inferred.

The purpose of treatment for patients with metastatic breast cancer is to maintain the patient's quality of life(QOL)with continued treatment for as long as possible.Eribulin was approved in April 2011 for the treatment of metastatic breast cancer, further increasing the selection of therapies available for the management of this disease.The current study presents a retrospective review of 31 patients who received eribulin in our hospital, and analyzes the factors related to the continuation and safety of its use.The median treatment continuation was 114 days(range, 8-281 days), and the treatment involved an average of 5 courses(range, 1-13 courses).There were no significant differences in the continuation of eribulin with regard to the number of previous chemotherapy regimens and modifications undergone by the patients.Neutropenia accounted for 80.6% of adverse eventsBGrade 3; however, the recovery was rapid.The rates of peripheral neuropathy and liver function failures were 12.9% and 6.5%, respectively. These results suggest that eribulin can be continued to be administered with the aim of maintaining QOL, and the therapy can be adjusted according to the patient's situation and the occurrence of adverse events by reducing the dose and treatment delays.

This case report discusses a 48-year-old woman with metastatic breast cancer: T4c(10.5 cm)N2bM1,(OSS, LYM), stage IV, estrogen receptor(ER)(+), progesterone receptor(PgR)(+), human epidermal growth factor receptor-2(HER2) (-), and Ki-67 17.2%. Administration of eribulin was initiated after treatment with anthracycline and taxane. Thereafter, 28 courses of eribulin maintained a SD state for over a year and improved the quality of life(QOL). Eribulin is effective for both prolonging life and improving QOL, which are the main goals in the treatment of metastatic or recurrent cancer. Therefore, this evidence suggests that eribulin can be effective in various clinical situations.

A goal for treating advanced disease is prolonging survival while maintaining a good quality of life(QOL). Eribulin chemotherapy may be suitable for this purpose. We report a case of advanced breast cancer with pathological complete response (pCR)obtained by eribulin chemotherapy. The patient was a 43-year-old woman who complained of a right mammary mass. A tumor measuring approximately 3 cm was palpated, and breast cancer was detected via ultrasound examination. Core needle biopsy indicated invasive ductal carcinoma based on histopathological findings. A metastasis to the supraclavicular lymph node was observed and was found to be malignant via fine-needle aspiration cytology. The patient was diagnosed with advanced breast cancer cT2N3M0, stage III C, Luminal B like. She underwent primary systemic therapy with 6 cycles of eribulin. The patient exhibited a clinical complete response to eribulin chemotherapy. Thereafter, a right mastectomy with level 3 axillary lymph node dissection was performed. Pathological diagnosis of the surgical specimen was pCR. At present, 3 years after surgery, the patient has no recurrence.

Obesitychanges the regulatorymechanisms of the immune system, resulting in impaired immunity. In cancer immune mechanisms, the greater the degree of obesity, the lower the activity of the lymphocytes. Herein, we examined the relationship between obesity and lymphocytes in breast cancer patients undergoing chemotherapy. We recruited 10 recurrent or metastatic breast cancer patients who were administered eribulin. Using bodymass index(BMI), we classified these patients into a non-obese group(BMI<25)and an obese group(BMI>25). We measured the number of lymphocytes before chemotherapy and 8 days after eribulin administration. We examined the decreasing rates of lymphocytes before and after eribulin administration in the 2 groups. The average age was 63.1 years. Non-obese and obese groups comprised 6 and 4 cases, respectively. The average rates of lymphocyte decrease before and after eribulin administration were 13.3%and 12.3% in the non-obese and obese groups, respectively. There were no significant differences between the 2 groups.

Clinical outcomes, including adverse events, in 52 advanced breast cancer patients treated with eribulin chemotherapy after taxane treatment (TX) were analyzed to confirm the effectiveness and safety of this treatment.The objective response rate (ORR) in patients was 34.6% (TX group 31.6%, non-TX group 36.4%). There were no significant differences in overall survival, time to treatment failure, or progression-free between three TX and non-TX groups. Further, adverse events did not differ between groups expression of neutropenia of Grade 3 or more. On the other hand, the number of patients with sensory peripheral neuropathy of Grade 1 or more was significantly more in the TX group than in the non-TX group. Eribulin chemotherapy was effective for the treatment of advanced breast cancer regardless of a history of taxane treatment.In addition, sensory peripheral neuropathy is a possible complication that can occur in advanced breast cancer patients treated with eribulin chemotherapy with taxane treatment history.

A 59-year-old woman with an exudative, reddish bilateral breast tumor and dyspnea visited our hospital. She was diagnosed as having scirrhous carcinoma with metastasis to the liver and pleural effusion, designated as Stage IV, hormone receptor positive, and human epidermal growth factor receptor-2 (HER2) negative. Systemic chemotherapy (3 regimens) and endocrine therapy (5 regimens) were administered for a total of 5 years 7 months. Eribulin was administered as fourth line systemic chemotherapy. The pleural effusion reduced and dyspnea improved. Her status was maintained for 1 year 3 months. This case suggests that eribulin may provide long-term survival and maintenance of quality of life (QOL) in metastatic breast cancer patients.

A 48-year-old woman was diagnosed with metastatic breast carcinoma and multiple bone metastases as well as a brain metastasis in 2004. Multiple bone metastases and brain metastases were also diagnosed in 2005, 2006, and 2010, but she remained stable with the use of chemotherapy and hormonal therapy for about 8 years. In 2013, severe anemia occurred, and the patient was diagnosed with microangiopathic hemolytic anemia (MHA). She was treated with eribulin(1.4 mg/m²), and recovered successfully after treatment. Approximately 8 months have elapsed after initiating the therapy, and there has been no recurrence. MHA associated with breast cancer is very rare, and is regarded as a disease with a poor prognosis. However, eribulin could be a valid treatment for prolonging the survival of patients with MHA associated with breast cancer.

Background: Eribulin mesylate, a novel non-taxane inhibitor of microtubule dynamics, results in a significant improvement in the overall survival of heavily pretreated patients with metastatic breast cancer(MBC). In the present study, we aimed to clarify the efficacy and safety of eribulin mesylate for the treatment of MBC., Patients and Methods: We examined 18 patients with MBC who received eribulin mesylate in our hospital from October 2011 to May 2013. The patients were assessed for therapeutic response and adverse events with this treatment; in addition, these parameters were assessed in patients undergoing a combination treatment of eribulin mesylate and trastuzumab., Results: The mean age of the patients in this study was 68.7 years(range, 60-85 years). All patients exhibited metastases to lymph nodes and distant sites. The mean number of prior regimens was 4.4(range, 2-9). The mean number of cycles of eribulin mesylate treatment administered was 7.2(range, 2- 17). The objective response rate and clinical benefit rate(PR+long SD)were 33.3%(6/18)and 50.0%(9/18), respectively, and the median progression-free survival was 6 months. The Grade 3/4 adverse events occurring in the patients included neutropenia in 13 patients(72.2%), anemia in 1 patient(5.6%), anorexia in 1 patient(5.6%), stomatitis in 1 patient(5.6%), and peripheral neuropathy in 1 patient(5.6%). However, 3 elderly patients who received the combination treatment of trastuzumab and eribulin mesylate experienced no adverse events., Conclusions: eribulin mesylate appears to demonstrate an acceptable tumor response in patients with MBC, and it can be safely administered to elderly patients if myelosuppression is carefully managed.

In the EMBRACE trial, eribulin was reported to significantly increase overall survival compared to treatment of the physician 's choice when given to patients with recurrent or metastatic breast cancer who had received prior treatment, including an anthracycline and a taxane. In April 2011, eribulin was approved in Japan for the treatment of inoperable or recurrent breast cancer. In this article, we report on the efficacy and safety of eribulin in cases we encountered. Twenty patients with advanced and recurrent breast cancer were administered eribulin in our hospital during the period from August 2011 to December 2012. The median age was 62 years(range, 42-76 years); 16 patients had the estrogen receptor(ER)(+)/human epidermal growth factor receptor 2(HER2)(-)subtype, whereas 4 patients had the triple-negative subtype. Following recurrence, the median number of chemotherapy regimens was 3(range, 0-5). Regarding the antitumor effects of eribulin, no cases showed complete response(CR), 5 cases showed partial response(PR), and 10 cases showed stable disease(SD); therefore, the response rate(CR+PR)was 25% and the clinical benefit rate(CR+PR+B6-month SD)was 35%. Median progression free survival was 146 days, and median overall survival was 482 days. In terms of adverse events(AEs), observed cases of hematotoxicity were of neutropenia(75%), leucopenia(75%), and anemia(80%). Cases of Grade 3 hematotoxicity or higher were of neutropenia(40%), leucopenia(20%), and febrile neutropenia(1 case, 5%). The observed non-hematotoxic AEs were peripheral neuropathy(30%)and general malaise(35%), although none were of Grade 3 or higher. The therapeutic efficacy of eribulin in the present study was relatively better than that in previous reports(EMBRACE trial, Japan Domestic 221 trial). The frequency of Grade 3 or higher AEs was low, and the drug was well tolerated. We believe that eribulin is a novel drug that provides therapeutic efficacy while maintaining quality of life(QOL).

The clinical outcomes, including adverse events, in 40 advanced breast cancer patients treated with eribulin were analyzed to confirm the effectiveness and safety of this treatment. The objective response rate (ORR) in patients was 35.0%. The median overall survival and time to treatment failure (TTF) in these patients was 479 and 63 days, respectively. Cases wherein eribulin was used as early-line treatment experienced significantly longer TTF compared to the cases wherein eribulin was used as late-line treatment; however, there was no difference in this value according to the breast cancer subtype. Moreover, subtype analysis revealed no significant difference in adverse events. We observed no difference in the benefit or tolerability of eribulin treatment among different breast cancer subtypes. However, our results suggest that a significant therapeutic effect can be expected when using eribulin as early-line treatment.

The patient was a 40-year-old woman who was aware of a tumor in her left breast that was gradually increasing in size. Ultrasonography revealed a hypoechoic mass with a skin cyst, approximately 3 cm in size, in the C area of the left breast. Core needle biopsy indicated estrogen receptor (ER) -negative, progesterone receptor (PR) -negative, and human epidermal growth factor receptor 2 (HER2) -negative squamous cell carcinoma. Overall examination did not indicate distant metastasis. A diagnosis of T4bN2aM0, stage IIIB triple-negative left breast cancer was made. Eribulin was administered at a dose of 1.4 mg/m2. The effect of eribulin was considered to be long-term stable disease( long-term SD). The patient did not experience severe adverse events during treatment. After 24 weeks of eribulin treatment, mastectomy of the left breast with axillary lymph node dissection was performed. At present, 1 year after surgery, the patient is alive with no recurrence. We conclude that eribulin chemotherapy is useful for the treatment of patients with squamous cell carcinoma of the breast.

Case 1: Case 1 involved a 42-year-old woman who had been diagnosed as having advanced breast cancer (Stage III B). She had previously received 6 courses of cyclophosphamide, epirubicin, and 5-fluorouracil CEF, 14 courses of weekly paclitaxel, and 2 courses of vinorelbine( VNR). After the courses of chemotherapy, she underwent modified radical mastectomy with axillary lymph node dissection. Two years after surgery, lung metastases were found, and the patient received 6 courses of weekly paclitaxel and 13 courses of nab-paclitaxel. However, the lung metastases progressed after the courses of chemotherapy, and therefore, we decided to administer eribulin as third-line chemotherapy. Eribulin was effective against the lung metastases for more than 1 year. Case 2: Case 2 involved a 52-year-old woman who had been diagnosed as having Stage IIB breast cancer. She had received 4 courses of CEF and 4 courses of docetaxel as neo-adjuvant chemotherapy. After chemotherapy, she underwent breast-conserving surgery with axillary lymph node dissection. Five years postoperatively, multiple liver metastases were found, and the patient received 3 courses. However, the liver metastases progressed after this chemotherapy. Subsequently, we administered nab-paclitaxel; however, it produced severe side effects. We then decided to administer eribulin as second-line chemotherapy. Eribulin was effective against the liver metastases for more than 1 year.

Eribulin mesylate, a novel microtubule inhibitor with a unique mechanism of action, was approved in Japan in April 2011 for the treatment of metastatic breast cancer patients who had been administered at least two prior chemotherapeutic agents. Here, we present a retrospective review of data from 27 patients who received eribulin monotherapy in our hospital. The overall response rate and clinical benefit rate were 25. 9% and 29. 6%, respectively, and the median progression-free survival was 9. 9 weeks(95% CI: 3. 5-16. 2 weeks). The toxicities of treatment were tolerable and manageable; responses were lower in patients who were triple negative subtype, and higher in patients who had responded to prior taxane treatment. The relative dose intensity of our data indicates that appropriate modification of dose and schedule may be an important part of eribulin monotherapy.