Outcome of eribulin as a late treatment line for Thai metastatic breast cancer patients

Chagkrit Ditsatham,1 Imjai Chitapanarux,2–4 Areewan Somwangprasert,1 Kirati Watcharachan,1 Panchaporn Wongmaneerung,1 Chaiyut Charoentum,5 Busyamas Chewaskulyong,5 Somvilai Chakrabandhu,2 Wimrak Onchan,2 Anongnart Teeyasuntranonn,6 Patumrat Sripan3 1Division of Head Neck Breast Surgery, 2Division of Radiation Oncology, 3Northern Thai Research Group of Radiation Oncology, 4Chiang Mai Cancer Registry, Maharaj Nakorn Chiang Mai Hospital, 5Division of Oncology, 6Pharmacy Division, Maharaj Nakorn Chiang Mai Hospital, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand Background: We report the safety and efficacy of eribulin as a late treatment line in Thai metastatic breast cancer (MBC) patients. Patients and methods: A total of 30 MBC patients treated with eribulin between January 2014 and January 2017 were retrospectively analyzed. The patients were scheduled to receive 1.4 mg/m2 of eribulin on day 1, day 8 and subsequently every 21 days. All patients had previously received at least three chemotherapy regimens including anthracycline and taxane. Response rate and progression-free survival (PFS) were analyzed. Results: The median age was 56 years (range, 40–74 years), with a median follow-up time of 5.7 months (range, 0.2–25 months). The overall response rate was 30% (nine patients): four patients had triple-negative breast cancer, three patients had luminal B breast cancer and two patients had luminal A breast cancer. The median PFS was 2.9 months (range, 0.2–14 months). The median number of previous chemotherapy regimens was 4 (range, 3–9). Univariate analysis showed that the number of regimens (four or fewer) prior to eribulin was statistically associated with superior PFS (P = 0.009). Multivariate analysis also showed similar statistical association between number of prior regimens (four or fewer) and better PFS adjusted by age group (≥50 years; hazard ratio = 1.29; 95% CI: 1.0–1.65; P = 0.046). There were no toxic deaths or grade 4 toxicities. Nine (30%) patients had grade 3 anemia toxicities, and the other common toxicities were leukopenia and neutropenia. Four (13%) patients required dose reduction and 16 (53%) patients required dose delay because of toxicities. Conclusion: Eribulin is an effective drug for heavily pretreated MBC patients with tolerable toxicities. The benefit was superior in patients who received fewer than four previous chemotherapy regimens. Keywords: eribulin, metastatic breast cancer, late treatment lin

Proximity Ligation Assay (PLA) to Evaluate DISC and MISC Composition

International audienceDistribution of the death receptor CD95 into lipid rafts (aggregation) and/or its internalization may contribute to the implementation of the apoptotic signal at the detriment of the non-apoptotic signaling pathway [1-6]. Also CD95 can form different protein complexes via dynamic protein-protein interactions (PPIs) according to its interaction with soluble or transmembrane CD95L. Therefore, spatiotemporal identification of these PPIs is pivotal to anticipate the signaling pathway implemented in cells stimulated with different forms of CD95L. Also, many disorders result from dysfunctions in terms of PPI subcellular distribution and/or their intensity, rendering evaluation of these features crucial to better understand pathogenesis.In situ proximity ligation assay (PLA) is a methodology that offers the possibility to identify PPIs and to determine where these PPIs occur in subcellular location (Fig. 1). Moreover, based on imaging, this method allows a quantification of PPIs at the cellular level and with a higher specificity than classical immunofluorescence assays. We here describe PLA used to confirm CD95/FADD interaction, a protocol that may serve to highlight other CD95 partners