Hormonal Therapy Resistant Estrogen-receptor Positive Metastatic Breast Cancer Cohort (HORSE-BC) Study : Current Status of Treatment Selection in Japan.

The Hormonal therapy resistant estrogen-receptor positive metastatic breast cancer cohort (HORSE-BC) study is a multicenter observational study evaluating the efficacy and safety of secondary endocrine therapy (ET) for postmenopausal cases of metastatic breast cancer (MBC) with poor response to primary ET. In this initial report we analyze the HORSE-BC baseline data to clarify the current status of treatment selection for MBC in Japan. Baseline data for the 50 patients enrolled in HORSE-BC were analyzed, including patient characteristics, types of secondary ET, and reasons for selecting secondary ET. Postoperative recurrence was detected in 84% of patients (42/50) and de novo stage IV breast cancer in 16% (8/50). Forty-one patients (41/50; 82%) received fulvestrant, 5 patients (10%) received selective estrogen receptor modulators (SERMs), 3 patients (6%) received ET plus a mammalian target of rapamycin (mTOR) inhibitor, and 1 patient received an aromatase inhibitor (AI) as the secondary ET. Forty-five patients selected their secondary ET based on its therapeutic effect, while 14 patients selected it based on side effects. Most patients with progression after primary ET selected fulvestrant as the secondary ET based on its therapeutic and side effects. We await the final results from the HORSE-BC study.

Higher efficacy and complete response with administration of eribulin for recurrent squamous cell breast carcinoma: A case report.

Squamous cell carcinoma is a rare histological type of breast cancer classified as metaplastic carcinoma. Metaplastic carcinoma involves differentiation of the breast glandular duct cells into mesenchymal tissues. While the chemotherapy regimen for metaplastic carcinoma is often similar to that for invasive ductal carcinoma, recurrence is associated with a poor prognosis due to the inadequate therapeutic efficacy of the regimen. We herein present the case of a 42-year-old female patient who underwent mastectomy of the right breast and right axillary node lymphadenectomy for T4N3aM0 breast cancer stage. The cancer was histopathologically diagnosed as squamous cell carcinoma of the breast. Adjuvant cyclophosphamide-epirubicin-fluorouracil (CEF) postoperative chemotherapy was administered, and lymphadenectomy of right-sided parasternal lymphatic metastases with pleural drainage was subsequently performed. Radiotherapy was administered to the thoracic wall and supraclavicular lymph nodes at 60 Gy. Positron emission tomography (PET)-computed tomography (CT) examination 3 months after the radiotherapy identified accumulation of fluorodeoxyglucose (FDG) in a supraclavicular lymph node and the thoracic wall; hence, a chemotherapeutic regimen with eribulin was initiated. At 11 months after initiation of eribulin, complete response was achieved, indicated by the absence of FDG accumulation in both the supraclavicular lymph node and the thoracic wall on PET-CT. The treatment efficacy of eribulin is considered to be a result of the mixed morphology of squamous cell carcinoma, including the presence of an epithelial component, such as adenocarcinoma cells, and a mesenchymal component, in the form of sarcomatoid cells. Eribulin displayed an effect similar to that of adriamycin against malignant soft tissue tumors and was shown to effectively target mesenchymal components. In cases of reduced expression of the DNA repair pathway components, such as in metaplastic carcinomas, eribulin may be more effective compared with adriamycin, the mechanism of action of which involves inhibition of DNA synthesis. A superior therapeutic effect was obtained with eribulin in squamous cell carcinoma. Therefore, eribulin appears to be a promising, effective therapeutic choice for the management of metaplastic carcinomas, including squamous cell carcinomas.

[A Case of Recurrent Breast Cancer with Carcinomatous Pleurisy Successfully Treated with Biweekly Paclitaxel and Bevacizumab].

A 72-year-old woman underwent mastectomy with axillary lymph node dissection for left breast cancer at the age of 43 years, and was diagnosed with breast cancer metastasis to the pleura at the age of 68 years. She had been sequentially treated with hormonal therapies, but complained of a cough and dyspnea after 4 years. Chest radiography showed right pleural effusion, and cytological examination of the pleural effusion revealed adenocarcinoma cells. Biweekly paclitaxel and bevacizumab therapy was administered. Two months later, the pleural effusion had disappeared. Biweekly paclitaxel and bevacizumab therapy was continued without any severe adverse events. After 30 months, the patient has remained free of carcinomatous pleurisy recurrence. Therefore, biweekly paclitaxel and bevacizumab therapy can be safely and effectively administered to elderly patients with carcinomatous pleurisy.

[An Elderly Patient with Metastatic Breast Cancer Who Developed Severe Adverse Events such as Stomatitis and Interstitial Pneumonia after Everolimus plus Exemestane Treatment].

An 80-year-old woman was diagnosed with right breast cancer with clinical Stage IIIA 6 years previously. She underwent mastectomy and axillary lymph node dissection. The pathological diagnosis was invasive micropapillary carcinoma with lymph node involvement. Immunohistochemically, the tumor was positive for estrogen receptor and progesterone receptor, and negative for HER2. Postoperatively, the patient was treated with adjuvant chemotherapy consisting of cyclophosphamide, epirubicin, 5-fluorouracil, and paclitaxel, followed by endocrine therapy with letrozole. Four years after surgery, she experienced a recurrence of breast cancer in the thoracic wall, and was treated with exemestane, toremifene, and fulvestrant for 1 year and 5 months. However, she developed carcinomatous pleurisy and was treated with eribulin. This last treatment was ineffective. Subsequently, she received combination therapy with everolimus and exemestane. Although the pleural effusion reduced markedly after 5 weeks, stomatitis, diarrhea, melena, and interstitial pneumonia occurred as adverse events. The symptoms improved after drug discontinuation and steroid therapy. The combination therapy with everolimus and exemestane is a prospective therapy for hormone-resistant recurrent breast cancer, but the management of adverse events is very important.

The prognosis in spindle-cell sarcoma depends on the expression of cyclin-dependent kinase inhibitor p27(Kip1) and cyclin E.

The aim of the present study was to examine the prognostic significance of p27(Kip1) and cyclin E expression in patients with spindle-cell soft tissue sarcomas. In 46 cases of spindle-cell sarcoma including 17 pre-operative biopsy materials, the expression of p27(Kip1) and cyclin E was immunohistochemically examined. The expression of p27(Kip1) decreased in the nuclei of metastatic primary tumor cells (stage IV), whereas the expression of cyclin E increased in those lesions. On univariate analysis, when the expression of p27(Kip1) and cyclin E was analyzed together, patients with spindle-cell sarcoma exhibiting low expression of p27(Kip1) and high expression of cyclin E showed lower distant-metastasis-free survival (DMFS) and overall survival (OS) than those with other combinations of the two parameters (both P < 0.0001). Multivariate analysis revealed that patients with low p27(Kip1) and high cyclin E expression also showed a decrease in DMFS (P = 0.0007, relative risk = 21.3) and OS (P = 0.005, relative risk = 20.8). These results suggest that the combination analysis of p27(Kip1) and cyclin E expression even in biopsy specimens allows the prediction of the clinical behavior of spindle-cell sarcoma.

Pedicle or free musculocutaneous flaps for shoulder defects after oncological resection.

Management of soft-tissue defects of the shoulder is described. Extensive defects of soft tissues with or without overlying skin were created after resection of sarcomas in five patients. Reconstruction was performed using musculocutaneous flaps, which included three pedicle latissimus dorsi and two free tensor fascia lata flaps. Simultaneous functioning replacement of the defects of the trapezius and deltoid muscles were each achieved in two patients. Primary wound healing was achieved, and each patient recovered good contour of the shoulder. Functional results were satisfactory in all patients with an average score of 93.4% (range, 83%-100%) using the system of the Musculoskeletal Tumor Society. The four functioning muscles recovered active contraction in the transferred position. The shoulder elevation was normal in three patients, and was 90 degrees and 30 degrees in one patient each. All patients remained disease-free at the time of latest follow-up. Thus, shoulder defects of the soft tissues can be managed appropriately with the two representative musculocutaneous flaps.

Survival analysis with p27 expression and apoptosis appears to estimate the prognosis of patients with synovial sarcoma more accurately.

BACKGROUND: Although recent experimental studies have implicated p27 as a regulator of apoptosis in a number of neoplasms, to the authors' knowledge the relation between p27 expression and apoptosis has not yet been established in synovial sarcoma. METHODS: The relation between p27, apoptosis, and clinicopathologic features were examined in 62 synovial sarcoma cases. RESULTS: p27 expression was found to be correlated inversely with the extent of apoptosis in synovial sarcomas. On survival analysis, p27 expression was found to be a significant and independent prognostic factor. Although the extent of apoptosis was determined to be prognostically significant, it failed to retain an independent and significant value on multivariate analysis. The combination of p27 expression and apoptosis allowed for the more accurate estimation of prognosis in patients with synovial sarcoma than either parameter alone. CONCLUSIONS: A combination of p27 expression and extent of apoptosis permitted the more accurate estimation ofy the prognosis of patients with synovial sarcoma.

Clinical significance of thallium-201 scintigraphy in bone and soft tissue tumors.

We evaluated sequential thallium scans on both early images (EI) and delayed images (DI) for 62 patients who had bone and soft tissue lesions. The purpose was to determine whether this technique could be used to ascertain accurately whether lesions were malignant or benign and to predict the response to chemotherapy. The thallium-201 chloride (201Tl) accumulation in malignant tumors and benign lesions was statistically different. Sensitivity, specificity, and accuracy for 201Tl scans in detecting malignant tumors was 94%, 65%, and 82%, respectively, for EI, and 94%, 85%, and 90%, respectively, for DI. On multivariate analysis, significant independent factors for 201Tl uptake were malignant lesions on EI and DI and high cellularity on EI. Thirteen patients with malignant bone and soft tissue tumors underwent 201Tl scans before and after preoperative chemotherapy. There was a good correlation between percentage of tumor necrosis and percentage change of accumulation in lesion-to-normal tissue ration, and the correlation coefficient was higher on EI ( r = 0.801) than on DI ( r = 0.664). These results support the notion that 201Tl scintigraphy, although showing some false-positive and false-negative findings, is a useful tool in the evaluation of either malignant tumors or benign lesions. Furthermore, 201Tl scans on EI provide benefit concerning the evaluation of chemotherapeutic response in patients with malignant bone and soft tissue tumors.