Secondary endpoints analysis in patients with estrogen receptor-positive metastatic breast cancer treated with everolimus and exemestane enrolled in Oral Care-BC.

BACKGROUND: The Oral Care BC-trial reported that professional oral care (POC) reduces the incidence and severity of oral mucositis in patients receiving everolimus (EVE) and exemestane (EXE). However, the effect of POC on clinical response among patients receiving EVE and EXE was not established. We compared outcomes for estrogen receptor-positive metastatic breast cancer patients who received POC to those who had not, and evaluated clinical prognostic factors. All patients simultaneously received EVE and EXE. METHODS: Between May 2015 and Dec 2017, 174 eligible patients were enrolled in the Oral Care-BC trial. The primary endpoint was the comparative incidence of grade 1 or worse oral mucositis, as evaluated for both the groups over 8 weeks by an oncologist. The secondary endpoints were progression-free survival (PFS) and overall survival (OS). Data were collected after a follow-up period of 13.9 months. RESULTS: There were no significant differences in PFS between the POC and Control Groups (P = 0.801). A BMI <  25 mg/m2 and non-visceral metastasis were associated with longer PFS (P = 0.018 and P = 0.003, respectively) and the use of bone modifying agents (BMA) was associated with shorter PFS (P = 0.028). The PFS and OS between the POC and control groups were not significantly different in the Oral-Care BC trial. CONCLUSIONS: POC did not influence the prognosis of estrogen receptor-positive metastatic breast cancer patients. Patients with non-visceral metastasis, a BMI <  25 mg/m2, and who did not receive BMA while receiving EVE and EXE may have better prognoses. TRIAL REGISTRATION: The study protocol was registered online at the University Hospital Medical Information Network (UMIN), Japan (protocol ID 000016109), on January 5, 2015 and at ClinicalTrials.gov ( NCT02376985 ).

The effect of denosumab in breast cancer patients receiving adjuvant aromatase inhibitors: 36-month results.

INTRODUCTION: Aromatase inhibitor (AI)-associated bone loss increases the risk of bone fracture and reduces patients' quality of life, making it a critical issue worldwide. We conducted a prospective non-randomized clinical trial (UMIN-CTR, UMIN 000016173) to assess the effect of denosumab on bone loss in patients treated with adjuvant AI and have previously reported the results at 12 and 24 months. This study aimed to present the results at 36 months of treatment with denosumab for osteopenia in breast cancer patients who were undergoing treatment with adjuvant AI; 36 months is the longest denosumab treatment period reported so far. MATERIALS AND METHODS: Patients received 60-mg denosumab subcutaneously every 6 months. Daily supplements containing 500-mg elemental calcium and at least 400 international units of vitamin D were highly recommended throughout the study period. The levels of bone mineral density (BMD) and bone turnover markers, serum tartrate-resistant acid phosphatase isoform 5b, and bone alkaline phosphatase were determined at baseline and 6, 12, 18, 24, and 36 months. RESULTS: At 36 months, the bone mineral density of the lumbar spine, right femoral neck, and left femoral neck were found to increase by 8.8% (95% confidence interval CI 7.6-10.1), 4.3% (95% CI 3.0-5.5), and 3.1% (95% CI 2.1-4.1), respectively. No non-traumatic clinical fractures occurred in patients receiving AI and denosumab. CONCLUSION: Twice-yearly administration of denosumab to the breast cancer patients treated with adjuvant AI, regardless of the skeletal site, resulted in consistent increases in BMD without severe adverse events at 36 months.

[A Case of Synchronous Bilateral Male Breast Cancer].

A 71-year-old man with right and left mammary tumor came to our hospital. Using needle biopsy, we diagnosed both tumors as ER-positive, PgR-positive, and HER2(1+)invasive ductalcarcinoma. We performed radicalmastectomy and axillary dissection. After surgery, the patient received postoperative chemotherapy, radiotherapy, and hormone therapy. The incidence of male breast cancer has been reported to be<1% of all breast cancer cases; only a few cases of simultaneous bilateral male breast cancer has been reported. Here, we report a rare case of synchronous bilateral male breast cancer.

Effects of denosumab on bone mineral density in Japanese women with osteoporosis treated with aromatase inhibitors for breast cancer.

Adjuvant aromatase inhibitor (AI) therapy, for hormone receptor-positive breast cancer, in postmenopausal women is associated with bone loss, leading to an increased risk of fractures. Denosumab, an antibody raised against the receptor activator of nuclear factor-κB ligand, has been proven to protect against AI-induced bone loss. Hence, we aimed to determine whether denosumab is effective in postmenopausal Japanese women with osteoporosis, treated with AI. We prospectively evaluated the bone mineral density (BMD) in the lumbar spine and the bilateral femoral neck in 102 postmenopausal women with clinical hormone receptor-positive breast cancer, stages I-IIIA, during a postoperative period of 12 months. The other inclusion criteria for this study were: women that should receive AIs as adjuvant therapy and those with evidence of osteoporosis (lumbar spine or bilateral femoral neck BMD, equivalent to T-score classification of ≤ - 2.5) upon enrollment. The patients received supplemental calcium, vitamin D, and 60 mg of subcutaneous denosumab every 6 months. The BMD of the lumber spine increased by 4.9 and 6.6% at 6 and 12 months, respectively. An increase in BMD was observed at the femoral neck, bilaterally. Hypocalcemia ≥ grade 2, osteonecrosis of the jaw, and non-traumatic clinical fracture were not observed in this study. Our findings revealed that biannual treatment with denosumab is associated with a great increase of BMD in Japanese women receiving adjuvant AI therapy, irrespective of their previous history of AI therapy.

Predictive factors for the efficacy of denosumab in postmenopausal Japanese women with non-metastatic breast cancer receiving adjuvant aromatase inhibitors: a combined analysis of two prospective clinical trials.

Aromatase inhibitors (AIs) are the gold standard therapy for breast cancer in postmenopausal women. AI suppresses the conversion of androgens to estrogens; however, this results in osteopenia, osteoporosis, and bone fracture, thus reducing the patient's quality of life. The use of adjuvant denosumab reduces the risk of clinical fractures in postmenopausal patients with breast cancer receiving AI. However, the efficacy of denosumab in the treatment of AI-associated bone loss has not been prospectively evaluated in Japan. In this study, we aimed to investigate the predictive factors for the efficacy of denosumab in postmenopausal patients with breast cancer treated with AI by analyzing the results of two prospective trials. The patients received 60 mg denosumab subcutaneously every 6 months. The primary endpoint was percentage change in lumbar spine bone mineral density (BMD) from baseline to month 12 in lumbar spine. Post hoc analysis and T tests were performed. A total of 205 patients were enrolled. At 12 and 24 months, the lumbar spine BMD increased by 5.6% [95% confidence interval (CI) 4.9-6.3] and 8.3% (95% CI 7.5-9.1), respectively. Subgroup analysis was conducted according to the time of AI therapy initiation, type of AI therapy, age, time since menopause, baseline body mass index, and BMD. The results showed that baseline lumbar and left femoral BMD was significantly associated with a percentage change in these sites, respectively. In addition, baseline left femoral BMD was also associated with a change in lumbar BMD. In conclusion, the baseline BMD in the lumbar spine was a predictive indicator for the efficacy of denosumab in this site and the baseline BMD in left femoral neck was a predictive indicator in lumbar spine and left femur.

Predictive factors for taxane acute pain syndrome determined by ordered logistic regression analysis.

This retrospective study was undertaken to identify predictive factors for developing taxane acute pain syndrome (TAPS) and to determine new strategies for improving QoL in patients undergoing chemotherapy. Between November 2010 and May 2018, we enrolled 121 breast cancer patients at our outpatient chemotherapy center who were undergoing chemotherapy with nanoparticle albumin-bound paclitaxel (nab-PTX) every 3 weeks. Variables related to the development of TAPS were extracted from the patients' clinical records and used for regression analysis. The degree of TAPS was classified as grade 0 = not developed; grade 1 = developed but did not require analgesics; grade 2 = developed but alleviated by analgesics such as acetaminophen or non-steroidal anti-inflammatory drugs (NSAIDs); or grade 3 = syndrome developed, causing sleep problems or interfering with daily living activities, but not alleviated by analgesics such as acetaminophen or NSAIDs thus requiring opioids. Multivariate ordered logistic regression analysis was performed to identify predictive factors for the development of TAPS. Significant factors identified for the development of TAPS included dose of nab-PTX (odds ratio (OR) = 11.717, 95% confidence interval (CI) = 11.6161-11.8182; P = 0.0421) and the administration of dexamethasone for up to 3 days (OR = 0.133, 95% CI = 0.0235-0.7450; P = 0.0223). In conclusion, a high dose of nab-PTX and the lack of dexamethasone administration for up to 3 days were identified as significant predictors of the development of TAPS.

[A Case of Breast Cancer with Parenchymal and Meningeal Central Nervous System Metastases Treated with Multimodality Therapy].

A 64-year-old woman who received neo-adjuvant chemotherapy and human epidermal growth factor receptor 2(HER2)- targeted therapy underwent modified radical mastectomy and axillary lymph node resection for HER2-positiveright breast cancer. After the surgery, chemotherapy, post-mastectomy radiation therapy, and HER2-targeted therapy were administered as adjuvant therapies. Two years and 6 months postoperatively, she complained of headaches and nausea. Magnetic resonance imaging showed brain metastasis, which was treated with gamma knife surgery. Two weeks later, she was urgently admitted to the hospital because of impaired consciousness. Based on cerebrospinal fluid cytology, she was diagnosed with meningeal metastasis of breast cancer. She developed hydrocephalus; thus, external ventricular drainage was performed, and a ventriculoperitoneal shunt was inserted. She was treated with whole-brain irradiation(30 Gy)and trastuzumab emtansine (T-DM1)as systemic therapy. Treatment of the patient was possible without recurrence continuously for over 12 months and with the maintenance of daily activities. The prognosis of patients with meningeal metastasis of breast cancer is extremely poor, and effective pharmacotherapy has not yet been established. T-DM1 may improvepatie nts' quality of lifeand the clinical outcomes of meningeal metastasis.

[A Case of Small Cell Carcinoma of the Breast].

A 67-year-old woman with a mass in the right breast was admitted to our hospital. The tumor measured 35mm in diameter in the right breast, and the lymph node measured 30mm in diameter in the right axilla. The mass was diagnosed as malignant based on core needle biopsy. Immunohistochemistry staining for synaptophysin, chromogranin A, and CD56 was positive, suggesting that the tumor was small cell carcinoma. Positron emission tomography-computed tomography imaging excluded any other primary disease. Thus, the patient was diagnosed as having primary small cell carcinoma of the breast. Modified radical mastectomy with axillary lymph node dissection was performed. The pathological diagnosis of the surgical material confirmed small cell carcinoma. The expression of estrogen, progesterone, and human epidermal growth factor receptors was negative. After surgery, chemotherapy- and radiotherapy-based breast cancer treatment were performed. The patient was relapse free 9 months after surgery.

Effect of denosumab administration on low bone mineral density (T-score -1.0 to -2.5) in postmenopausal Japanese women receiving adjuvant aromatase inhibitors for non-metastatic breast cancer.

Although adjuvant aromatase inhibitor (AI) therapy is widely used in postmenopausal women with hormone receptor-positive breast cancer, it is known to be associated with bone loss and increased fracture risk. Denosumab, a fully human monoclonal antibody against the receptor activator of nuclear factor-κB ligand, has been shown to protect against AI-induced bone loss. However, the efficacy of denosumab in the treatment of AI-associated bone loss has not been prospectively evaluated in Japan. We prospectively monitored bone mineral density (BMD) of the lumbar spine and bilateral femoral necks in 100 postmenopausal women with hormone receptor-positive postoperative breast cancer of clinical stage I-IIIA in whom treatment with AI as adjuvant endocrine therapy was planned or had been ongoing. Study participants received supplemental calcium and vitamin D every day and denosumab (60 mg) subcutaneously every 6 months. At enrollment, patients were required to have evidence of low bone mass without meeting the criteria for osteoporosis. The primary endpoint was percentage change from baseline in lumbar spine BMD at month 12. At 6 and 12 months, lumbar spine BMD increased by 3.3 and 4.7%, respectively. BMD of the femoral necks also increased. Hypocalcemia of grade ≥2, osteonecrosis of the jaw, and non-traumatic clinical fracture did not occur. In conclusion, semi-annual treatment with denosumab was associated with increased BMD in Japanese women receiving adjuvant AI therapy, regardless of prior AI treatment.

[A Case of Bone Marrow Carcinomatosis of Occult Breast Cancer Treated Effectively with Fulvestrant].

A 63-year-old woman experienced left cervical lymph node swelling since May 2012. Based on PET-CT findings, metastases of a malignant tumor to the mediastinal, axillary, and left cervical lymph nodes were suspected. Her left cervical lymph node biopsy revealed metastatic carcinoma of occult cancer, because no primary tumor could be identified despite the specific examinations. She rejected further therapeutic intervention. In July 2013, she was admitted because of anemia, cardiac failure, and fever. She was diagnosed with bone marrow carcinomatosis from occult cancer based on her bone marrow biopsy. Metastatic breast cancer was mostly considered because she tested positive for estrogen and progesterone receptors, CA15-3 levels were increased, and her axillary lymph nodes were swollen. Fulvestrant and zoledronic acid were administered and continued for 20 months, with improvement in anemia and tumor marker levels, and also maintenance of partial response.

[Experience of Fulvestrant for Hormone Receptor-Positive HER2-Negative Advanced and Metastatic Breast Cancer].

Several cases of hormone receptor-positive HER2-negative advanced and recurrent breast cancer treated with fulvestrant (FUL)were retrospectively investigated to assess the efficacy and safety of the treatment. FUL was administered to a total of 41 patients-33 with recurrent and 8 with Stage IV cancer-from January 2012 to September 2016. The median number of lines that used FUL was 3, the median time to treatment failure(TTF)was 7 months, the overall response rate(RR)was 19.5%, and the clinical benefit rate(CBR)was 53.6%. Our result was similar to those of the FIRST and the FALCON studies, which showed a decrease in RR after the fourth-line. With regard to RR, FUL seemed to provide better results at Cthird-lines of treatment. While a shorter TTF was seen in the cases with liver metastases, a longer TTF was seen in the cases with soft tissue metastases. Therefore, it may be helpful to consider the site of metastasis when predicting the effects of FUL.

[A case of stage IV breast cancer with long-term partial response treated with tri-weekly paclitaxel plus bevacizumab].

Paclitaxel combined with bevacizumab yields significantly better progression-free survival (PFS) in patients with metastatic breast cancer than paclitaxel alone. Here, we report a case of stage IV breast cancer with multiple liver, lung, and bone metastases maintaining a long-term partial response (PR) with tri-weekly paclitaxel plus bevacizumab administration. A 46- year-old woman treated with endocrine therapy for 21 months for multiple metastases in her lungs and bones detected 4 years after surgery for left breast cancer was referred to our hospital. New metastases were discovered in her liver. She received paclitaxel (l 90 mg/m/(2)) on days 1, 8, and 15 combined with bevacizumab (10 mg/kg) on days 1 and 15 every 4 weeks. However, during the first 3 courses, the administration of paclitaxel on day 8 was postponed to 1 to 2 weeks because of severe neutropenia. We began tri-weekly administration of paclitaxel plus bevacizumab. She continued receiving the treatment for about 1 year, without severe side effects. The PR state with good performance status was maintained. We suggest that the tri-weekly administration of paclitaxel plus bevacizumab is an effective way to maintain long-term efficacy.

The Feasibility of Omission of Postoperative Radiotherapy in Japanese Patients With Early Breast Cancer Treated With Breast-Conserving Surgery.

Background This study was aimed at analyzing the impact of postoperative radiotherapy (PORT) after breast-conserving surgery (BCS) on Japanese patients with early-stage breast cancer and exploring the potential of PORT omission. Materials and methods Data from 794 patients with early-stage breast cancer (T1-2, N0-1), who underwent BCS with (n = 310) or without PORT (n = 484) were retrospectively analyzed. Local control (LC) rate and breast cancer-specific survival (BCSS) were compared between the groups that received and did not receive PORT in the whole cohort and low-risk cohort (i.e., the cohort with negative surgical margin, lymph node negativity, and estrogen receptor positivity, excluding young age of 49 or less), and in low-risk subgroup using propensity-score matching. Results PORT was associated with better LC but not BCSS in the total population. In the low-risk cohort, the incidence of local recurrence in patients without and with PORT was 5.3% and 4.8%, respectively, at 10 years (p = 0.591), and 7.8% and 4.8%, respectively, according to propensity-score matching (p = 0.485). Conclusion PORT improved LC in the total population, but not BCSS or overall survival (OS). In the low-risk group analysis (negative surgical margin, lymph node negativity, estrogen receptor positivity, and age 50 years or more), equivalent LC, BCSS, and OS were found including propensity-matched comparison. Therefore, this study showed that the omission of PORT could be a treatment option for low-risk Japanese patients. Further multi-center prospective studies are warranted to validate these findings and reduce the unnecessary burden of PORT for patients and institutions.

Breast cancer subtype and distant recurrence after ipsilateral breast tumor recurrence.

BACKGROUND: There is little information about the impact of breast cancer subtype on prognosis after ipsilateral breast tumor recurrence (IBTR). METHODS: One hundred eighty-five patients were classified according to breast cancer subtype, as approximated by estrogen receptor, human epidermal growth factor receptor 2 (HER2), and Ki-67, of IBTR, and we evaluated whether breast cancer subtype was associated with distant recurrence after IBTR. RESULTS: There was a significant difference in distant disease-free survival (DDFS) after IBTR according to breast cancer subtype defined by a cutoff of the Ki-67 index of 20 % (p = 0.0074, log-rank test). The 5-year DDFS rates for patients with luminal A, luminal B, triple-negative, and HER2 types were 86.3, 57.1, 56.6, and 65.9 %, respectively. In addition, breast cancer subtype was significantly associated with distant recurrence after IBTR on adjustment for various clinicopathologic factors (p = 0.0027, Cox proportional hazards model). CONCLUSIONS: Our study suggests that breast cancer subtype based on immunohistochemical staining predicts the outcomes of patients with IBTR. Further analyses are needed (UMIN-CTR number UMIN000008136).

Myoid hamartoma of the breast that proved difficult to diagnose: a case report.

Myoid hamartomas of the breast are extremely rare breast lesions, with a poorly understood pathogenesis. We describe the case of a 38-year-old premenopausal woman who presenting with a mass in the left breast. Mammography revealed an oval mass that was partly indistinct, and ultrasonography showed a hypoechoic mass with a slightly irregular margin. Bilateral breast dynamic magnetic resonance imaging was performed for a more detailed evaluation. The images showed rapid initial enhancement and a microlobulated margin. Because the suspicion of malignancy was strong at that time, core needle biopsy was performed. Histologically, the tumor was identified as fibroadenoma. A case of myoid hamartoma of the breast that proved difficult to diagnose is reported, and discussed with reference to the literature.

[A case of metastatic pancreatic cancer which trastuzumab+capecitabine combination therapy was effective].

A 61-year-old woman presented with carcinoma of the left breast(T2N1M0, stage II B), which enforced left Bt+R1. In May 2008, the patient underwent preoperative chemotherapy consisting of 4 courses of FEC 75(fluororracil, epirubicin, and cyclophosphamide). Pathological examination revealed that the lesion was a papillotubular carcinoma,(ER-, PgR-, HER2 3+). In September, 2009, CT scans revealed metastases of the cervical lymph nodes and pancreas. Examination of biopsy specimens from the left cervical lymph nodes revealed that the metastases were from breast cancer(ER-, PgR-, HER2 3+). To treat the recurrences, combination therapy with trastuzumab+capecitabine was introduced in October, 2009. CT scans obtained in May 2010 revealed complete response of the metastases of the lymph nodes and pancreas. It is difficult to distinguish a metastases from a primary pancreatic cancer, but the present case was considered to be one of metastic pancreatic cancer because the findings were in agreement with the expression time of lymph node metastasis. Follow-up CT scans revealed that CR was maintained by the combination therapy of trastuzumab+capecitabine.

[A case of breast cancer with brain metastases responding to paclitaxel and capecitabine therapy].

A 31-year-old woman was referred to our hospital for back pain. After a close investigation, she was diagnosed with multiple bone, liver and brain metastases of breast cancer. She was administered a combination therapy of paclitaxel and capecitabine. Capecitabine was administered orally at 628mg/m / 2 twice daily on days 1-21, and paclitaxel 80 mg/m2 was injected on days 1, 8, and 15. Both drug courses were repeated every 28 days. After 5 courses of treatment, the level of tumor markers and all metastases were reduced. The combination treatment of paclitaxel and capecitabine is considered to be effective for metastatic breast cancer with brain metastases.

[Administration of nab-paclitaxel for 9 metastatic breast cancer patients].

Nab-paclitaxel was administered to 9 patients with refractory advanced or recurrent breast cancer from 1 to 8 times(median 4)triweekly. The median cumulative dose was 775mg/m2(range 260-2, 000), and the median delivered dose intensity was 66. 7mg/m2/week(range 58. 3-86. 7). The response to treatment was CR in one patient, PR in 2 patients, SD in one patient, and PD in 4 patients. In one patient, treatment had to be suspended because of grade 3 peripheral neuropathy. The clinical benefit was 33%. All 4 PD patients were administered other salvage treatments and are alive. Adverse events included 6 case of neutropenia(grade 3-4 in 4 cases), grade 3 AST/ALT elevations in one patient, grade 3 myalgia in one patient. No case of febrile neutropenia was seen. All reactions were under control except for one patient with grade 3 peripheral neuropathy. Concurrent trastuzumab administration was safe also. In conclusion, nab-paclitaxel could be administered safely, and may contribute to the treatment of refractory advanced or recurrent breast cancer.

[A case of effective lapatinib/capecitabine therapy for HER2-positive breast cancer with multiple brain metastases].

A 63-year-old woman was suffering from HER2-positive and hormone receptor-negative breast cancer with bone metastasis. She received 16 cycles of paclitaxel(PTX 80mg/m2)plus trastuzumab(TRA 2mg/kg)on a 7-day cycle, and zoledronic acid(ZOL 4mg/body every 28 days), resulting in a near clinical complete response(cCR). Two years later, the patient complained of dizziness and nausea, and magnetic resonance imaging revealed multiple brain metastases. The prior treatments with PTX and TRA were changed to lapatinib(LAP)(orally at 1, 250mg/day every day)and capecitabine(CAP)(orally at 2, 000mg/m2 every day for 2 weeks, followed by a 1-week rest interval as 1 cycle)because of the multiple brain metastases. After 4 cycles of treatment, the number of brain lesions and the tumor sizes were significantly reduced. After 7 cycles, however, magnetic resonance imaging revealed the deterioration of some brain lesions. After whole-brain irradiation(30 Gy in 10 fractions)was added to the treatment, the outcome was near cCR. In conclusion, combination therapy of Lap and Cap may be an effective treatment option for brain metastasis of HER2-positive breast cancer.

Effectiveness of eribulin as first-line or second-line chemotherapy for HER2-negative hormone-resistant advanced or metastatic breast cancer: findings from the multi-institutional, prospective, observational KBCRN A001: E-SPEC study.

BACKGROUND: The optimal positioning of eribulin treatment remains unclear. This study aimed to investigate the effectiveness of eribulin administration as first- and second-line chemotherapy in patients with endocrine-resistant advanced or metastatic breast cancer (AMBC) in the real-world clinical setting. METHODS: This multi-institutional prospective cohort study enrolled patients with triple-negative AMBC or estrogen receptor-positive AMBC refractory to at least one previous endocrine therapy. The overall survival (OS) from the start of first-line (OS1) and second-line chemotherapy (OS2) was assessed. Data analysis included real-world chemotherapy sequences of first- to third-line chemotherapy regimens. The adjusted hazard ratio (HR) with 95% confidence interval (CI) for treatment regimen comparison was calculated using a stratified proportional hazards model. RESULTS: Among 201 patients enrolled, 180 were included in the final analysis. Eribulin was administered as first- and second-line chemotherapy to 46 (26.6%) and 70 (47.9%) patients, respectively. Median OS1 and OS2 were 2.25 (95% CI 1.07-2.68) and 1.75 (95% CI, 1.28-2.45) years for first- and second-line eribulin, respectively. Oral 5-FU followed by eribulin had a numerically longer OS1 (2.84 years) than the other sequences. Among patients who proceeded to second-line or later chemotherapy, the median OS1 for those treated with anthracycline or taxane as first- or second-line (n = 98) was 2.56 years (95% CI 2.27-2.74), while it was 2.87 years (95% CI 2.20-4.32) for those who avoided anthracycline and taxane as first- and second-line (n = 48) (adjusted HR, 1.20; 95% CI 0.70-2.06). In the exploratory analysis, OS1 was 2.55 (95% CI 2.14-2.75) and 2.91 years (95% CI 2.61-4.32) for those aged < 65 and ≥ 65 years, respectively (adjusted HR of ≥ 65, 0.91; 95% CI 0.56-1.46). CONCLUSIONS: Eribulin or oral 5-FU administration in first- and second-line chemotherapy without anthracycline/taxane was acceptable in the real-world setting. TRIAL REGISTRATION: This study is registered with Clinical Trials.gov (NCT 02,551,263).