Acute toxicity of nonylphenols and bisphenol A to the embryonic development of the abalone <Emphasis Type="Italic">Haliotis diversicolor supertexta</Emphasis>

Acute toxic effects and mechanisms of two typical endocrine disrupting chemicals, nonylphenols (NPs) and bisphenol A (BPA), to the embryonic development of the abalone Haliotis diversicolor supertexta, were investigated by the two-stage embryo toxicity test. The 12-h median effective concentrations (EC₅₀) of NPs and BPA to the trochophore development were 1016.22 and 30.72 μg L⁻¹, respectively, and the respective 96-h EC₅₀ values based on the completion of metamorphosis (another experimental endpoint) were reduced to 11.65 and 1.02 μg L⁻¹. Longer exposure time and magnified exposure concentrations in the benthic diatom, that serves as both food source and settlement substrate during the metamorphosis, via bioaccumulation, led to the higher sensitivity of metamorphosis to target EDCs compared with the trochophore development. The hazard concentrations for 5% of the species (HC₅) could be employed as the safety thresholds for the embryonic development of the abalone. The 12-h HC₅ values of NPs and BPA were 318.68 and 13.93 μg L⁻¹, respectively, and the respective 96-h HC₅ values were 0.99 and 0.18 μg L⁻¹, which were at environmentally relevant levels. Results of proteomic responses revealed that NPs and BPA altered various functional proteins in the abalone larvae with slight differences between each chemical and affected various physiological functions, such as energy and substance metabolism, cell signalling, formation of cytoskeleton and cilium, immune and stress responses at the same time, leading to the failure of metamorphosis.     

Eribulin-based neoadjuvant chemotherapy for triple-negative breast cancer patients stratified by homologous recombination deficiency status: a multicenter randomized phase II clinical trial

Breast Cancer Research and Treatment - To investigate clinical usefulness of eribulin-based neoadjuvant chemotherapy in triple-negative breast cancer (TNBC) patients. Patients in group A...     

Durable complete response in HER2-positive breast cancer: a multicenter retrospective analysis

Purpose

Though advanced and metastatic epidermal growth factor receptor 2 (HER2)-positive disease is not curable, a small proportion of patients with HER2-positive metastatic breast cancer remain in prolonged complete remission with anti-HER2 treatment. We hypothesized that some cases of HER2-positive metastatic breast cancer may be curable. In this large, multicenter retrospective study, we aimed to assess the long-term outcomes for patients with a durable response to trastuzumab.

Methods

We retrospectively evaluated the data of patients diagnosed with HER2-positive metastatic breast cancer who received trastuzumab for more than 2 years as the first-line treatment. Patients diagnosed between April 1, 2001 and December 31, 2014 at 19 institutions in Japan were included in the analysis. From 124 potential subjects, 16 were excluded and 108 were evaluated.

Results

The median follow-up length was 7.7 years. Disease progression occurred in 44/108 (40.7%) patients and 13/108 (12%) patients died. The median progression-free survival was 11.2 years, and as more than 80% of patients were alive 10 years after metastatic breast cancer diagnosis. Of the 108 patients, 57 achieved a clinical complete response. Trastuzumab therapy was interrupted for 27 (47.4%) of these patients (based on the doctor’s recommendation for 19 patients, owing to adverse events for 4 patients, owing to unknown reasons for 3 patients, and at the request of 1 patient). Disease progression occurred in 4 of the 27 patients after the interruption of trastuzumab treatment. The median duration of trastuzumab therapy for all 27 patients was 5.1 years (0.9–9.3 years).

Conclusion

We found that some patients showed no evidence of disease after the interruption of trastuzumab therapy. Discontinuation of maintenance trastuzumab in this patient population after a limited time should be explored cautiously while awaiting a global collaborative effort for a randomized trial.