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Assisted reproductive technology (ART) has progressed rapidly, resulting in a great improvement in the clinical pregnancy ratio. When applying the protocol of piezo intracytoplasmic sperm injection (Piezo-ICSI), it is very important to puncture the zona pellucida and the oocyte cytoplasmic membrane without rupturing the oocyte cytoplasmic membrane. Previous studies have shown that the poor extensibility of the oocyte cytoplasmic membrane might be closely related to rupture. However, no consensus has been reached regarding how the quality of the oocyte for extensible ability or rupture possibility affects the surfaces of the oocyte on the microscopic frames. We conducted this study to provide evidence that artificial intelligence (AI) techniques are superior for predicting the tendency of oocyte rupture before puncturing on Piezo-ICSI. To inspect it, we provided a retrospective trial of 38 rupture oocytes and 55 nonruptured oocytes. This study marked the highest accuracy of 91.4% for predicting oocytes rupture using the support-vector machine method of machine learning. We conclude that AI technologies might serve an important role and provide a significant benefit to ART.

One of the problems during the intracytoplasmic sperm injection (ICSI) procedure is unintentional membrane rupture (UMR), which often predisposes to subsequent oocyte degeneration. Can the ICSI Position Detector (IPD) be useful in identifying the optimal puncture location to prevent UMR during ICSI?A total of 709 mature oocytes were included. Conventional ICSI was carried out and images were recorded by IPD; these were analysed retrospectively.Inseminated oocytes were retrospectively grouped according to the IPD, irrespective of whether oolemma was punctured at an area in which UMR is likely (non-appropriate group) or unlikely (appropriate group). In the appropriate group, rates of UMR (5.3% versus 18.2%) and degeneration (2.5% versus 8.7%) were significantly lower than those of the non-appropriate group, whereas rate of fertilization (87.1% versus 69.7%) was significantly higher than those of the non-appropriate group, respectively (P0.001). These differences remained even after propensity score matching to adjust for potential differences in characteristics between appropriate and non-appropriate groups.This study demonstrated that the IPD is useful to identify the optimal puncture location to circumvent UMR during the ICSI procedure, resulting in reduced UMR and oocyte degeneration, thereby, generating more embryos available for transfer or cryopreservation.

Genipin was reacted with benzylamine and several amino acids to prepare gardenia blue (GB). The time-course of GB formation with benzylamine was monitored by high-performance liquid chromatography (HPLC), liquid chromatography time-of-flight mass spectrometry (LC-TOFMS), and

Background: Nab-paclitaxel(nab-PTX) is improved taxane in terms of solubility, alcohol-free and reduced incidence of anaphylaxis. On the other hand, chemotherapy-induced peripheral neuropathy (PN) is known as a major adverse event which was failed to suppress by many medications. Recently, some reports describe about cooling and compression of extremities of patients treated by taxane can reduce the incidence and severity of PN. The efficacies of interventions with frozen groves and compression stockings to prevent nab-PTX-induced PN was examined.Methods: The patients with HER2 negative primary breast cancers treated by four cycles of nab-PTX pre-/post- operative chemotherapies were randomized to two groups (interventions with frozen groves (FG) and compression stockings (CS), and with standard care (SD)). Primary endpoint was frequency and time to onset of >Grade 2 PN by CTCAE ver.4.0, and secondary endpoints are frequency of >Grade2 PN at the end of four cycles of nab-PTX, HRQOL, recovery of PN for 5 years from the end of nab-PTX and safety. Also, we requested to keep diary with several questions for patient reported outcomes (PRO).Results: Of the 124pts enrolled, 123(62 FG/CS, 61 SD) were included in the intent-to-treat analysis. There were no significant differences in clinicopathological findings between two groups. As a primary endpoint, frequency and time to onset of >Grade 2 motor-PN /sensory-NP of hands comparing FG and SD showed p=0.162/0.599, and of foots comparing CS and SD showed p=0.525/0.933 (Log-rank test with one sided significant level of 10%). Conversely, the worst Grade of sensory-PN is statistically significant difference at Cycle 2 (p=0.021; Mann-Whitney’s U-test with two-sided significant level of 5%), >Grade3 of motor-PN was statistically significant low in all cycles (p=0.022; Log-rank test with one sided significant level of 10%), >Grade1 of sensory-PN was statistically significant low (p=0.022; Log-rank test with one sided significant level of 10%), and >Grade3 of sensory-PN was statistically significant low in all cycles (p=0.072; Log-rank test with one sided significant level of 10%) with FG in detail. In addition, Grade3 of motor-PN was statistically significant low in all cycles (p=0.022; Log-rank test with one sided significant level of 10%), >Grade1 of sensory-PN was statistically significant low (p=0.015; Log-rank test with one sided significant level of 10%), and >Grade3 of sensory-PN was statistically significant low in all cycles (p=0.089; Log-rank test with one sided significant level of 10%)in all cycles (p=0.022; Log-rank test with one sided significant level of 10%) with CS in detail. Moreover, PRO indicated by patients’ diary showed interesting patterns of increase and decrease in sense of pain and paralyzed which might be corresponding to efficacy of interventions with FG and CS.Conclusion: Although primary endpoints were not met by the interventions with FG and CS, this trial revealed the detail of PN caused by nab-PTX, and these interventions might delay beginning of sensory and motor PN and reduce the worst grade of PN. The adverse events grading according to CTCAE and PRO indicated by patients’ diary seems to be not completely matched, the usefulness of FG and CS are investigating with more questionnaire. (UMIN: UMIN000016902) Citation Format: Masahiro Kashiwaba, Takahiro Nakayama, Takafumi Sangai, Takashi Morimoto, Hiroyuki Yasojima, Yutaka Yamamoto, Shinji Ohno, Norikazu Masuda. A randomized phase II trial of interventions with frozen groves and compression stockings to prevent nab-paclitaxel induced chemotherapy-induced peripheral neuropathy (SPOT trial) [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS9-52.

The formation of tetra-n-butylammonium bromide (TBAB) hydrate from a TBAB aqueous solution tends to show a supercooling phenomenon, which is non-ideal for the practical use of TBAB hydrate. However, as reported in the literature, the products obtained from the use of metal electrodes for the application of an electric field can accelerate the nucleation of the hydrate. Herein, we investigated the role of metal particles (Ag, AgBr, Zn, and ZnO) and their mixed forms (Ag–AgBr and Zn–ZnO) on promoting the nucleation of TBAB semiclathrate hydrate. The nucleation-promoting effect was most significant for the mixed metal particles when prepared by simultaneous grinding of the metal particle components. The changes in the physicochemical properties of the mixed metal particles as a result of grinding were believed to accelerate the nucleation of TBAB hydrate.

Transient receptor potential vanilloid 2 (TRPV2) channels are expressed and play functional roles in various immune cells. Physical stimuli leading to TRPV2 activation causes mast cell degranulation. Besides their roles in immune cells, it has been shown that TRPV2 channels are pathophysiologically relevant to degenerative muscular diseases such as dilated cardiomyopathy and muscular dystrophy. Hence, development of drug candidates that inhibit human TRPV2 activation is an urgent matter. NK-4, a cryptocyanine dye, inhibited agonist-induced TRPV2 activity in mouse TRPV2-transfected HEK293 cells. However, it remains unclear whether NK-4 exerts regulatory effects on the activation of human TRPV2 channels. In this study, we show that NK-4 inhibits intracellular Ca

An ice slurry is a mixture of fine ice particles and an aqueous solution. Because of the latent heat of fusion of the ice particles and the wide heat exchange areas, ice slurries have many advantages as a thermal energy storage medium. The flow and heat transfer characteristics of ice slurries have been intensively studied. In the present study, the flow characteristics of an ice slurry were assessed experimentally, focusing on the distribution of the ice packing factor (IPF) and the energy losses on passing through a T-junction under laminar flow conditions. The ice slurry was produced from on a 5 mass% ethanol solution, and the inlet IPF, the Reynolds number for the inlet flow, and the flow rate ratio were all varied while monitoring the pressure drop and IPF before and after the junction. The results show that the distribution of IPF values is affected by the inlet IPF, and that the pressure drop before and after the T-junction increases along with the inlet IPF and the Reynolds number. This study also determined the branch loss coefficients for both the branch and main tubes as a means of evaluating the energy losses associated with branching.

The heat transfer characteristics of phase change emulsions (PCEs) with solidification of phase change material (PCM) particles in a circular tube have been investigated. PCEs containing 10 wt% n-hexadecane were emulsified with the surfactants polyoxyethylene sorbitan monostearate (Tween 60) and polyoxyethylene sorbitan monooleate (Tween 80). The experiments were performed with a double-tube type heat exchanger. The PCE flowed inside the inner tube and was cooled from the outside. The supercooling phenomenon of the PCM particles inside the PCEs was confirmed, while the PCEs flowed inside the tube even though they were cooled below the melting point of the PCM. Furthermore, the solidification start temperatures of the PCM particles inside the flowing PCEs were almost the same when they were cooled under static conditions. The heat transfer performance of the PCEs improved when solidification of the PCM particles was in progress. The type of surfactant affected the solidification start temperature of the PCM particles, but it did not significantly affect the heat transfer performance.

Purpose Our primary objective was to determine the benefit/risk of anthracycline-free regimens by comparing docetaxel + cyclophosphamide (TC) alone, fluorouracil + epirubicin + cyclophosphamide (FEC) followed by TC, or TC followed by FEC as a primary treatment for patients with HR-positive, HER2-negative BC. Methods We randomized patients with stage I–III HR-positive HER2-negative, operable BC to receive either six cycles of TC (TC6), three cycles of FEC followed by three cycles of TC (FEC-TC), or three cycles of TC followed by three cycles of FEC (TC-FEC). The primary endpoint was the pathological response. Secondary endpoints included clinical response, type of surgical procedure, recurrence, death, and adverse events (by NCI-Common Terminology Criteria for Adverse Events v.3.0). We conducted all statistical analyses using SAS Version 9.2. Results We enrolled 195 patients and analyzed data from 193 as the intention-to-treat population. Pathological complete response rates were numerically higher in the TC6 group than in the other groups (p = 0.321). The breast conservation rate was significantly higher in the TC6 group (73%) than in the other groups (FEC-TC 51%, TC-FEC 45%, p = 0.007). Adverse events with grade > 3 were not common in the treatment groups (p = 0.569). The overall and distant disease-free survivals were similar among the groups with median follow-up of 5.80 years. Conclusions Despite similar long-term efficacy and safety profile, the higher breast conservation rate in the TC6 group suggests that preoperative chemotherapy without an anthracycline may benefit patients with HR-positive HER2-negative BC. Trial registration UMIN000003283 https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000003873.

Background Vascular endothelial growth factor (VEGF) is a key player in angiogenesis, and bevacizumab, a humanized monoclonal antibody against VEGF-A, is already utilized in daily clinical practice coupled with chemotherapy for locally advanced and metastatic breast cancers (ABC). Although the impact of bevacizumab plus paclitaxel therapy on PFS was prominent, no OS benefit has been demonstrated so far. Identification of a robust biomarker for bevacizumab therapy in terms of benefit on OS is a critical issue. Since VEGF modulates various functions of cancer immunity, direct inhibition of VEGF, in addition to vascular normalization by bevacizumab may lead to improvement of immune microenvironment, resulting in favorable prognosis in patients. On the basis of this aspect, predictive efficacy of peripheral immune related parameters were investigated in patients treated with bevacizumab plus paclitaxel. Method A total of 182 patients with locally advanced and metastatic breast cancers treated with bevacizumab plus paclitaxel were retrospectively recruited from three institutes. We measured neutrophil-to-lymphocyte ratio (NLR), absolute lymphocyte count (ALC), and c-reactive protein (CRP) in the peripheral blood taken at baseline (the same day just before start of 1st treatment). Bevacizumab 10 mg/kg on days 1 and 15 and paclitaxel 80 or 90 mg/m2 on day 1, 8, and 15 of each 28-day cycle were administered intravenously. The cut-off values of NLR, ALC, and CRP were set at 3, 1500/μL, and 1.0mg/dL, respectively and baseline values of these factors were measured. Results We divided the patients into NLR-high (n=101) and -low (n=81); CRP-high (n=62) and -low (n=89). The progression-free survival (PFS) of patients with NLR-low was significantly longer than that of patients with NLR-high (median, 12.6 vs. 7.2 months; hazard ratio (HR), 0.47; 95% confidence interval (CI), 0.31-0.70; p=0.0002). In addition, OS of patients with NLR-low was significantly better than those with -high (22.2 vs. 13.5 months; HR, 0.55; 95% CI, 0.38-0.80; p=0.0017). Similarly, improved PFS and OS were recognized in patients with CRP-low as compared with -high (HR, 0.42; 95% CI, 0.27-0.66; p Citation Format: Hiromi Ozawa, Yoshimasa Miyagawa, Ayako Yanai, Takehiro Yanagawa, Jyunichi Inatome, Chiyomi Egawa, Arisa Nishimukai, Kaori Takamoto, Takashi Morimoto, Atsushi Sata, Reiko Fukui, Ayako Bun, Tomoko Higuchi, Yukie Fujimoto, Michiko Imamura, Yasuo Miyoshi. Baseline neutrophil-to-lymphocyte ratio and C-reactive protein predict efficacy of bevacizumab plus paclitaxel therapy for locally advanced or metastatic breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-08-49.

Background: Neoadjuvant anti-HER2 target agents combined with anthracycline and taxane is now considered a standard regimen for human epidermal growth factor receptor 2 (HER2)-positive breast cancer. A less toxic, non-anthracycline regimen has been considered as a treatment option for patients with node-negative small tumors. Estrogen receptor-negative and HER2-positive (pure HER2) tumors are more likely to achieve a pathological complete response (pCR). This study evaluates the activity and safety of neoadjuvant nanoparticle albumin-bound paclitaxel (nab-PTX) plus trastuzumab for pure HER2 breast cancer in patients with low risk of relapse. Patients and Methods: We treated patients with tumors measuring ≤3 cm, node-negative, pure HER2 breast cancer using neoadjuvant nab-PTX 260 mg/m2 with trastuzumab every 3 weeks for 4 cycles. The primary endpoint was the pCR rate. The secondary endpoints included the clinical response rate, pathologic response rate (defined as pCR or minimal residual invasive disease only in the breast), breast-conserving surgery conversion rate, safety, and disease-free survival. Depending on the pathological findings of surgical specimens, the administration of adjuvant anthracycline could be omitted. The accrual of 30 patients was planned. This study was registered with ClinicalTrials.gov, number NCT02598310 and University hospital Medical Information Network-Clinical Trials Registry, number UMIN000019616. Results: This study was terminated without the expected number owing to slow accrual. In total, 18 patients were enrolled. No patient required dose delays or reductions; none showed disease progression, and all patients underwent surgery as scheduled. Of the 18 patients, 66.7% achieved pCR, and the adjuvant anthracycline regimen was omitted for all patients. The incidence of severe adverse events was quite low. Observed grade 3 adverse events included neutropenia (6%), liver enzyme elevation (11%), and allergic reaction to infusion of trastuzumab (6%). Notably, sensory peripheral neuropathy was observed in a substantial number of patients (88%), but there were no severe events. Discussion: The primary outcome observed in this study is not inferior to that reported in previous studies which were administered the standard regimens with trastuzumab combined with anthracycline and taxane. Therapeutic strategies that achieve pCR using efficient and effective neoadjuvant therapy with fewer adverse effects and lower cost are advantageous. On the other hand, originally, as many patients with small tumors who met eligible criteria of this study does not need mastectomy, they are less likely to benefit from breast conserving surgery due to tumor shrinkage effect by neoadjuvant therapy. It is conceivable that there were a certain number of patients who selected primary surgery rather than neoadjuvant therapy of this study. In conclusion, this less toxic, anthracycline-free regimen appears to be a significantly effective neoadjuvant therapy for patients with pure HER2 breast cancer at low relapse risk. Citation Format: Satoru Tanaka, Hirotaka Morishima, Naofumi Oda, Nobuki Matsunami, Tsutomu Takashima, Satoru Noda, Shinichiro Kashiwagi, Yukie Tauchi, Yuka Asano, Kosei Kimura, Hiruya Fujioka, Risa Terasawa, Kanako Kawaguchi, Ayana Ikari, Takashi Morimoto, Shintaro Michishita, Toshihiro Kobayashi, Junna Sakane, Toshikatsu Nitta, Nayuko Sato, Norihiro Hokimoto, Yukihiro Nishida, Mitsuhiko Iwamoto. A phase 2 study of de-escalated neoadjuvant therapy with nanoparticle albumin-bound paclitaxel and trastuzumab for low risk pure HER2 breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-16-32.

The effect of bevacizumab plus paclitaxel therapy on progression-free survival (PFS) is prominent; however, no overall survival (OS) benefit has been demonstrated. Our aim was to study the predictive efficacy of peripheral immune-related parameters, neutrophil-to-lymphocyte ratio (NLR), absolute lymphocyte count (ALC), and c-reactive protein (CRP) in locally advanced and metastatic breast cancers. A total of 179 patients treated with bevacizumab plus paclitaxel were recruited from three institutes in the test cohort. The cut-off values of NLR, ALC, and CRP were set at 3, 1500/μL, and 1.0 mg/dL, respectively, and baseline values of these factors were measured. The PFS of patients with NLR-low was significantly longer than that of patients with -high (median, 12.6 vs. 7.2 months; hazard ratio (HR), 0.48, 95% confidence interval (95% CI), 0.31–0.73; p = 0.0004). OS of patients with NLR-low was significantly better than those with-high (22.2 vs. 13.5 months; HR, 0.57, 95% CI, 0.39–0.83; p = 0.0032). Similarly, improved PFS and OS were recognized in patients with CRP-low as compared with patients with -high (HR, 0.44, 95% CI, 0.28–0.68; p = 0.0001 and HR, 0.39, 95% CI, 0.26–0.61, p < 0.0001, respectively). In the validation cohort from two institutes (n = 57), similar significant improvements in PFS and OS were confirmed for patients with NLR-low (p = 0.0344 and p = 0.0233, respectively) and CRP-low groups (p < 0.0001 and p = 0.0001, respectively). Low levels of NLR and CRP at baseline were significantly associated with improved prognosis in patients treated with bevacizumab plus paclitaxel.

Hypertension is a major risk factor for cardiovascular diseases, and behavior modification has been shown to improve blood pressure (BP). We investigated whether daily self-monitoring of systemic BP and other factors related to cardiovascular events decreased BP in hypertensive participants. In this prospective, randomized, open, blinded-endpoint trial, we assigned 161 participants with hypertension to monitor their BP daily (BP-measurement group) or, in addition to BP, monitor their body fat, sleeping time, and daily step count (multiple-measurement group) or no self-monitoring (control group) for 2 months. The primary endpoint was the absolute change in systolic BP from baseline to 2 months after assignment. There were no differences in the baseline age and gender ratios among the three groups. After 2 months, systolic BP in the morning was unchanged in the control group, at a median of 149 mmHg [interquartile range (IQR) 136-164] from 150 mmHg (IQR 138-164), and was significantly decreased to 139 mmHg (IQR 125-148) from 142 mmHg (IQR 131-157) in the BP-measurement group. BP did not further decrease in the multiple-measurement group, 134 mmHg (IQR 121-146) from 141 mmHg (IQR 131-157). Daily self-monitoring of BP decreased the BP of participants with hypertension, but additional daily self-monitoring of body fat, sleeping time, and daily step count did not further decrease BP. This behavior modification merits use as a nonpharmacological hypertension treatment.

Our aim was to investigate the efficacy and safety of initial neoadjuvant endocrine therapy with exemestane alone followed by tailored treatment, either continued exemestane monotherapy or exemestane plus docetaxel–cyclophosphamide (TC) combination therapy, in postmenopausal patients with primary invasive estrogen receptor–positive, human epidermal growth factor receptor 2–negative, stage I‐IIIA breast cancer and Ki67 labeling index ≤30%. In this open‐label phase II study, patients initially received exemestane 25 mg/d for 12 weeks. Responders were defined as patients who achieved complete response (CR), partial response (PR) with Ki67 labeling index ≤5% after treatment, or stable disease with Ki67 labeling index ≤5% both before and after treatment. For the subsequent 12 weeks, exemestane monotherapy was continued for responders (group A), whereas nonresponders received exemestane plus four cycles of TC (docetaxel 75 mg/m2 and cyclophosphamide 600 mg/m2 every 3 weeks) (group B). Clinical response rate (ie the proportion of patients with CR or PR) at 24 weeks was the primary endpoint. Of 64 patients provisionally enrolled between December 2010 and May 2016, 58 (median age 60 years) started the study treatment. Five patients discontinued treatment in the initial exemestane monotherapy period, and 39 completed the study treatment. Clinical response rates at 8‐12 and 24 weeks were 71% (10/14, 95% confidence interval [CI] 41.9%‐91.6%) and 57% (8/14, 95% CI 28.9%‐82.3%), respectively, in group A, and 16% (4/25, 95% CI 4.5%‐36.1%) and 56% (14/25, 95% CI 34.9%‐75.6%), respectively, in group B. Grade ≥3 adverse events were reported in 8% (1/15) and 53% (20/38) in group A and group B, respectively. The tailored treatment maintained the favorable clinical response to exemestane alone in responders and improved clinical response in nonresponders. Trial number UMIN000004752 (UMIN Clinical Trials Registry)., Change in Ki67 labeling index over the course of the study in patients receiving continued exemestane monotherapy (A) and those receiving exemestane plus docetaxel–cyclophosphamide) (B).

While some studies show improved outcomes in clinical trial participants as compared to non-participants, existence of such a trial effect has not been proved precisely. This was a prospective cohort study to compare the prognoses for participants in the randomized controlled trial (SELECT BC) and non-participants. SELECT BC compared S-1 and taxane as first-line treatment for metastatic breast cancer. Non-participants were all patients who met the eligibility criteria of SELECT BC and who had been requested to participate in that trial by attending doctors and declined. The study aimed to compare the prognoses between participants and non-participants. The primary endpoint was median overall survival. The median OS in participants was significantly superior to that in non-participants with a statistically significant difference (36.8 months vs. 25.2 months. HR 1.48, p = 0.022). A similar result was obtained when only patients who received the same chemotherapy (S-1 or taxane) used in SELECT BC after declining participation were assumed as non-participants (36.8 months vs. 22.0 months. HR 2.03, p = 0.006). This study may suggest the existence of a trial effect, in which, for a given treatment, participation in a clinical trial is associated with a better outcome.

In this study, the supercooling characteristics of PCM particles in PCEs cooled at constant temperature were investigated experimentally, based on the assumed use of PCEs in practical applications. n-hexadecane (melting point: 291.35 K) and n-octadecane (melting point: 301.35 K) were used as the dispersed PCMs. The mean PCM particle diameter and surfactant type were varied as experimental parameters, and the PCEs were subjected to various supercooling degrees and cooling times. The experimental results showed that the mean PCM particle diameter, supercooling degree, and cooling time of the PCE affected the freezing ratio of the PCM particles, when the PCE was prepared with Tween 80. When the PCE was prepared with Tween 60 or polyvinyl alcohol as the surfactant (which had similar structures to the PCM), the cooling time did not significantly affect the freezing ratio.

Aim To investigate the efficacy and safety of initial neoadjuvant endocrine therapy with exemestane (EXE) alone followed by tailored treatment: continued EXE monotherapy for responders or EXE plus docetaxel–cyclophosphamide (TC) combination therapy for non-responders. Methods This open-label phase II study enrolled postmenopausal patients with primary invasive estrogen receptor (ER)-positive, HER2-negative, stage I–IIIA (T1c–T3 N0–2 M0) breast cancer and Ki67 index ≤30%. Patients first received EXE 25 mg/day for 12 weeks. Based on clinical response and change in Ki67 index, responders were defined as patients who achieved complete response (CR), partial response (PR) with Ki67 index ≤5% after treatment, or stable disease (SD) with Ki67 index ≤5% both before and after treatment. Non-responders were defined as patients with PR and Ki67 index >5% after treatment, or SD and Ki67 index >5% before or after treatment. For the subsequent 12 weeks, responders continued EXE monotherapy (continued EXE group) and non-responders received EXE plus 4 cycles of TC (docetaxel 75 mg/m2 and cyclophosphamide 600 mg/m2 every 3 weeks) (EXE+TC group). Primary endpoint was clinical response (CR and PR) at week 24. Results A total of 58 patients (median age 60 years, range 53–67 years) were enrolled between December 2010 and May 2016. Five patients discontinued treatment in the initial 12-week EXE monotherapy period; therefore 53 received the subsequent treatment. After 8–12 weeks of initial EXE monotherapy, 15 patients were classified as responders (8 with PR and Ki67 index ≤5% after treatment, 7 with SD and Ki67 index ≤5% before and after treatment) and 38 as non-responders (5 with PR and Ki67 index >5% after treatment, 33 with SD and Ki67 index >5% before or after treatment). Clinical response rates at weeks 12 and 24 were 71% (10/14, 95%CI 41.9–91.6%) and 57% (8/14, 95%CI 28.9–82.3%), respectively, in the continued EXE group, and 16% (4/25, 95%CI 4.5–36.1%) and 56% (14/25, 95%CI 34.9–75.6%), respectively, in the EXE+TC group. At week 24, no significant difference was found in median Ki67 index between the continued EXE and EXE+TC groups (1.4% and 2.0%, respectively). The proportion of patients with preoperative endocrine prognostic index (PEPI) 0 was higher in the continued EXE than in the EXE+TC group (60% vs 29%), but not significantly so (P=0.058, Fisher's exact test). The breast-conserving surgery rate was 93% and 56% (continued EXE and EXE+TC groups, respectively). Adverse events (AEs) ≥grade 3 were reported in 40% (21/53) of patients (continued EXE group 8%, 1/15; EXE+TC group 53%, 20/38). The most common AEs were leukopenia (37%, 14/38), neutropenia (32%, 12/38), and febrile neutropenia (16%, 6/38) during chemotherapy (EXE+TC group). Conclusion Tailored treatment maintained the favorable clinical response to EXE alone in responders and improved subsequent clinical response in non-responders. EXE+TC was associated with higher incidence of hematological AEs, but these were manageable. The results show the effectiveness of tailored neoadjuvant endocrine and chemoendocrine therapy in postmenopausal ER-positive breast cancer patients. (JBCRG-11TC; UMIN000004752) Citation Format: Yasojima H, Sato N, Masuda N, Morimoto T, Ueno T, Kanbayashi C, Kaneko K, Saji S, Sasano H, Morita S, Ohno S, Toi M. Neoadjuvant exemestane or exemestane plus docetaxel and cyclophosphamide tailored by clinicopathological response to 8–12 weeks' exemestane exposure for ER+/HER2– postmenopausal breast cancer patients [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-14-07.

Purpose The prognosis of human epidermal growth factor receptor 2 (HER2)-positive locally advanced or metastatic breast cancers (MBCs) has dramatically improved due to the introduction of trastuzumab, pertuzumab, and trastuzumab emtansine (T-DM1). The efficacy of T-DM1 is prolonged for some patients; however, the predictive factors remain unknown. There is a report that T-DM1 induced antitumor immunity in patients treated with neoadjuvant therapy, with tumor infiltrating lymphocytes (TILs) increasing after the administration of T-DM1. Based on these observations, the benefits of T-DM1 for prognosis may be mediated by an immune reaction against breast cancers, at least in part. As an indicator of cancer immunity, in addition to TILs, the neutrophil-to-lymphocyte ratio (NLR) has been established in early breast cancers. In the present study, we investigated the usefulness of the NLR for treatment efficacy of T-DM1 in HER2-positive MBCs. Methods Fifty-three advanced or metastatic breast cancers treated with T-DM1 were retrospectively recruited from three institutes. The NLR in the peripheral blood was measured at baseline (just before the start of T-DM1) and after one cycle (just before the start of cycle 2). The cutoff value of the NLR was set at 2.56 (median value) and progression-free survival (PFS) and overall survival (OS) according to NLR levels were evaluated. Results The PFS of patients with NLR-low at baseline (NLR Citation Format: Imamura M, Morimoto T, Egawa C, Miyagawa Y, Miyoshi Y. Significance of baseline neutrophil-to-lymphocyte ratio for progression-free survival of patients with HER2-positive locally advanced and metastatic breast cancer treated with trastuzumab emtansine [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-10-19.

Emulsions are mixtures of two immiscible liquids, which are important in various fields such as the food, cosmetics, and pharmaceutical industries. In industrial situations, natural convection may occur inside an emulsion owing to the temperature differences in the emulsion manufacturing and storage processes. Therefore, it is important to understand the natural convection characteristics of an emulsion for effective design of such systems. In the present study, oil-in-water (O/W) emulsions were prepared and the natural convection characteristics of the oil particles of the emulsions inside a rectangular vessel heated from one vertical wall and cooled from the opposite wall were investigated experimentally. Silicone oil was used as the dispersed phase of the O/W emulsion. The test samples were prepared with various oil particle sizes and oil volume fractions. We found that multiple convection layers formed inside the emulsion depending on the wall temperature difference, oil particle size, and oil volume fraction. Furthermore, the Nusselt number of an emulsion with a high oil volume fraction was higher than that of a single-phase fluid.