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Background Entinostat is an oral inhibitor of class I histone deacetylases intended for endocrine therapy-resistant patients with hormone receptor-positive (HR+) advanced or metastatic breast cancer (BC). We examined the safety, efficacy, and pharmacokinetics of entinostat monotherapy and combined entinostat/exemestane in Japanese patients. Methods This phase 1 study (3 + 3 dose-escalation design) enrolled postmenopausal women with advanced/metastatic HR+ BC previously treated with nonsteroidal aromatase inhibitors. Dose-limiting toxicities (DLTs) of entinostat monotherapy (3 mg/qw, 5 mg/qw, or 10 mg/q2w) and entinostat+exemestane (5 mg/qw + 25 mg/qd) were assessed. Pharmacokinetics, lysine acetylation (Ac-K), and T-cell activation markers were measured at multiple time points. Results Twelve patients were enrolled. No DLTs or grade 3–5 adverse events (AEs) occurred. Drug-related AEs (≥ 2 patients) during DLT observation were hypophosphatemia, nausea, and platelet count decreased. Six patients (50%) achieved stable disease (SD) for ≥ 6 months, including one treated for > 19 months. Median progression-free survival was 13.9 months (95% CI 1.9–not calculable); median overall survival was not reached. Area under the plasma concentration-time curve and Ac-K in peripheral blood CD19+ B cells increased dose-proportionally. The changing patterns of entinostat concentrations and Ac-K levels were well correlated. T-cell activation markers increased over time; CD69 increased more in patients with SD ≥ 6 months vs. SD Conclusions Entinostat monotherapy and combined entinostat/exemestane were well tolerated in Japanese patients, with no additional safety concerns compared with previous reports. The correlation between pharmacokinetics and Ac-K in peripheral blood CD19+ B cells, and also T-cell activation markers, merits further investigation. Trial registration JAPIC Clinical Trial Information, JapicCTI-153066. Registered 12 November 2015. ClinicalTrials.gov, NCT02623751. Registered 8 December 2015.

Background Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse effect of paclitaxel (PTX). There is no known prophylactic measure, although there are some reports of prevention with compression therapy using surgical gloves. On account of its predominantly subjective symptoms, it is difficult to exclude bias when assessing for CIPN. In this study, we assessed the effectiveness of the same procedure for the prevention of paclitaxel-induced PN based on a double-blind study design. Methods The patients with early and recurrent breast cancer (with no prior PTX exposure) initiating weekly chemotherapy with PTX 80 mg/m2 were enrolled. Each patient donned two gloves on each hand at every PTX infusion. Two one-size-smaller gloves were donned on one hand (study side) and two normal-size gloves were donned on the other hand (control side) during 90 min from 30 min before the infusion to 30 min after the end of the infusion. Study side are blind for both patients and assessing physicians according to determination of the study side by research nurses in the chemotherapy unit. The primary outcome was the difference in the frequency of CIPN (motor/sensory) determined by the physician using the common terminology criteria for adverse events (CTCAE v4.0), with an evaluation at each cycle of PTX infusion. McNemar test was used to assess the primary outcome. Results Between July 2017 and November 2018, 56 patients were enrolled and 49 patients were evaluated. Overall, Grade ≥ 2 PN (sensory) was observed in 30.6 and 36.7% in the study and control sides, respectively (McNemar p = 0.25). PN (motor) was observed in 4.1 and 6.1% in the study and control sides, respectively (McNemar p = 1.0). Conclusion Surgical glove compression therapy showed no statistically significant effect on the incidence of PTX-induced PN. Trial registrations This study was registered with the University Hospital Medical Information Network (UMIN) Clinical Trials Registry managed by the National University Hospital Council of Japan (UMIN000027944). Registered 26 June 2017.

Background The pathological and clinical features of invasive lobular carcinoma (ILC) differ from those of invasive ductal carcinoma (IDC). Several studies have indicated that patients with ILC have a better prognosis than those with ductal carcinoma. However, no previous study has considered the molecular subtypes and histological subtypes of ILC. We compared prognosis between IDC and classical, luminal type ILC and developed prognostic factors for early breast cancer patients with classical luminal ILC. Methods Four thousand one hundred ten breast cancer patients were treated at the Aichi Cancer Center Hospital from 2003 to 2012. We identified 1,661 cases with luminal IDC and 105 cases with luminal classical ILC. We examined baseline characteristics, clinical outcomes, and prognostic factors of luminal ILC. Results The prognosis of luminal ILC was significantly worse than that of luminal IDC. The rates of 5-year disease free survival (DFS) were 91.9 % and 88.4 % for patients with luminal IDC and luminal ILC, respectively (P = 0.008). The rates of 5-year overall survival (OS) were 97.6 % and 93.1 % for patients with luminal IDC and luminal ILC respectively (P = 0.030). Although we analyzed prognosis according to stratification by tumor size, luminal ILC tended to have worse DFS than luminal IDC in the large tumor group. In addition, although our analysis was performed according to matching lymph node status, luminal ILC had a significantly worse DFS and OS than luminal IDC in node-positive patients. Survival curves showed that the prognosis for ILC became worse than IDC over time. Multivariate analysis showed that ILC was an important factor related to higher risk of recurrence of luminal type breast cancer, even when tumor size, lymph node status and histological grade were considered. Conclusions Luminal ILC had worse outcomes than luminal IDC. Consequently, different treatment approaches should be used for luminal ILC than for luminal IDC. Electronic supplementary material The online version of this article (doi:10.1186/s12885-016-2275-4) contains supplementary material, which is available to authorized users.