Neoadjuvant Chemotherapy with or without Concurrent Hormone Therapy in Estrogen Receptor-Positive Breast Cancer:NACED-Randomized Multicenter Phase II Trial

Although in the neoadjuvant setting for estrogen receptor (ER)-positive breast cancers, chemotherapy or hormone therapy alone does not result in satisfactory tumor response, it is unknown whether concurrent chemo-endocrine therapy is superior to chemotherapy alone in clinical outcomes. We conducted a randomized phase II trial to test the responses of ER-positive patients to concurrent administration of chemo-endocrine therapy in the neoadjuvant setting. Women with stage II-III, ER-positive, invasive breast cancer (n=28) received paclitaxel followed by fluorouracil, epirubicin, cyclophosphamide (T-FEC) and were randomized to receive concurrent chemo-endocrine therapy consisting of goserelin administered subcutaneously for premenopausal women or an aromatase inhibitor for postmenopausal women. The primary endpoint was the pathological complete response (pCR) rate after neoadjuvant therapy. Twenty-eight patients were randomized. There were no significant differences in pCR rate between the concurrent group (12.5%;2/16) and the chemotherapy alone group (8.3%;1/12). Tumor size after therapy was significantly reduced in the concurrent therapy group (p=0.035), but not in the chemotherapy-alone group (p=0.622). Neoadjuvant chemotherapy with concurrent hormone therapy provided no significant improvement in pCR rate in ER-positive breast cancers. These preliminary results should be followed up by further studies

Estrogen receptor (ER) mRNA expression and molecular subtype distribution in ER-negative/progesterone receptor-positive breast cancers

We examined estrogen receptor (ER) mRNA expression and molecular subtypes in stage I-III breast cancers that are progesterone receptor (PR) positive but ER and HER2 negative by immunohistochemistry (IHC) or fluorescent in situ hybridization. The ER, PR, and HER2 status was determined by IHC as part of routine clinical assessment (N = 501). Gene expression profiling was done with the Affymetrix U133A gene chip. We compared expressions of ESR1 and MKI67 mRNA, distribution of molecular subtypes by the PAM50 classifier, the sensitivity to endocrine therapy index, and the DLDA30 chemotherapy response predictor signature among ER/PR-positive (n = 223), ER-positive/PR-negative (n = 73), ER-negative/PR-positive (n = 20), and triple-negative (n = 185) cancers. All patients received neoadjuvant chemotherapy with an anthracycline and taxane and had adjuvant endocrine therapy only if ER or PR > 10 % positive. ESR1 expression was high in 25 % of ER-negative/PR-positive, in 79 % of ER-positive/PR-negative, in 96 % of ER/PR-positive, and in 12 % of triple-negative cancers by IHC. The average MKI67 expression was significantly higher in the ER-negative/PR-positive and triple-negative cohorts. Among the ER-negative/PR-positive patients, 15 % were luminal A, 5 % were Luminal B, and 65 % were basal like. The relapse-free survival rate of ER-negative/PR-positive patients was equivalent to ER-positive cancers and better than the triple-negative cohort. Only 20-25 % of the ER-negative/PR-positive tumors show molecular features of ER-positive cancers. In this rare subset of patients (i) a second RNA-based assessment may help identifying the minority of ESR1 mRNA-positive, luminal-type cancers and (ii) the safest clinical approach may be to consider both adjuvant endocrine and chemotherapy

Anomalous aggregation state of deuterium molecules in the nanoscale pores of a metal organic framework

The behavior of hydrogen molecules adsorbed onto the nanospace of porous materials is of great interest but is poorly understood. Here we show direct visualization of deuterium molecules adsorbed on isoreticular metal organic frameworks IRMOF-1 at 77 K using reverse Monte Carlo simulation based on first principle molecular dynamics simulation and neutron diffraction. Results show that the two types of adsorption sites around a ZnO4 cluster are almost fully occupied by the deuterium molecules but that other sites are not fully occupied. Moreover an interesting information about the aggregation state of deuterium molecules was directly obtained from the deuterium–deuterium partial pair distribution function. Namely, the average distance of deuterium molecules adsorbed onto IRMOF-1 is slightly longer than that in a solid state but much shorter than that in the corresponding gas state

Simultaneous in situ measurements of contact behavior and friction to understand the mechanism of lubrication with nanometer-thick liquid lubricant films

A high-performance microscopic observation system was developed and integrated with a purpose-built pin-on-disk type tribotester. This allows for simultaneous in situ measurements of the vertical displacement and friction force of a pin sliding on disks lubricated with nanometer-thick liquid films at velocities up to 0.1 m/s, with accuracies of approximately 0.6 nm and 10 μN. Upward pin displacement was observed, exhibiting an exponential increase followed by a slight increase with increasing sliding velocity. The pin displacement also increased with film thickness and lubricant viscosity. We conclude that even nanometer-thick liquid lubricant films can generate upward dynamic pressure. Further insight into the shearing process was gained by analyzing the measured friction forces using the Eyring thermal activation energy approach

Percutaneous Cardiopulmonary Support System for the Treatment of Fulminant Myocarditis

We have developed a simple percutaneous cardiopulmonary support (PCPS) system. The circuit of the system is set up and sterilized beforehand and can be used promptly in an emergency situation. We used the PCPS on three patients with fulminant myocarditis and treated them successfully. Case 1 was a 53-yr-old man and Case 2 was a 12-yr-old girl. They had failed to respond to treatment of their circulatory states with conventional therapy. Their circulatory states improved dramatically after application of PCPS with 2 L/min blood flow. They were weaned from PCPS after 107 and 227 hours use, respectively. Case 3 was a 37-yr-old woman who developed ventricular fibrillation which was resistant to drug therapy and cardioversion. After starting PCPSwith4 L/min blood flow, arrhythmia disappeared and her circulatory state improved. She was successfully weaned after 39-hour of PCPS. Patients with fulminant myocarditis fall into circulatory collapse which is resistant to conventional therapy, but there is a possibility that cardiac function will recover after the acute phase of myocarditis. Therefore, PCPS can be the only treatment of the circulatory collapse of fulminant myocarditis, which is refractory to conventional therapy

Bi-weekly eribulin therapy for metastatic breast cancer: a multicenter phase II prospective study (JUST-STUDY)

Background: This study aimed to investigate whether schedule modification is safe and effective in patients intolerant to the standard eribulin dose and schedule. Methods: Patients with metastatic breast cancer (MBC) treated with both anthracycline and taxane and ≤ 3 prior regimens of chemotherapy for MBC received eribulin at the standard dose and schedule (1.4 mg/m² on days 1 and 8 of a 21-day cycle) in the first cycle; change of dosing schedule (1.4 mg/m² on days 1 and 15 of a 28-day cycle) was determined by change in neutrophil count, platelet count, aspartate aminotransferase, alanine aminotransferase, total bilirubin, serum creatinine, and non-hematological toxicity on day 8 of the first cycle or day 1 of the second cycle. Clinical benefit rate (CBR; primary endpoint), time to treatment failure (TTF), overall survival (OS), and safety were evaluated. Results: Of the 88 patients who were enrolled and received standard eribulin therapy in the first cycle, 42 patients were moved to the bi-weekly therapy group and 40 continued standard therapy. In the bi-weekly and standard therapy groups, mean relative dose intensity was 62.7 and 90.9%, CBR was 31.0 and 25.0%, median TTF was 81.5 and 75 days, and OS was 523 and 412 days, respectively. Neither group reported severe adverse events. Conclusion: This is the first study to show that a bi-weekly eribulin schedule is tolerable and has comparable efficacy in patients intolerant to the standard eribulin schedule