A retrospective safety and efficacy analysis of the first patients treated with eribulin for metastatic breast cancer in Stockholm, Sweden

<div><p></p><p><b>Backgrounds.</b> Eribulin is a non-taxane, microtubule dynamics inhibitor approved for the treatment of patients with metastatic breast cancer (MBC) in Europe in March 2011.</p><p><b>Material and methods.</b> For the purpose of an internal quality control, all patients with MBC treated with eribulin at Karolinska University Hospital were registered in a database. Clinical data were collected retrospectively for patients that were registered by August 2012 and safety and efficacy of eribulin were evaluated. Treatment toxicity including fatigue, neurotoxicity and infection was graded according to CTCAE v4.0. Objective response to treatment was investigated using routinely performed radiological assessments. When only clinical assessments were made, the evaluation of the treating physician was used. Furthermore, the efficacy of eribulin was investigated in different tumor subtypes.</p><p><b>Results.</b> Forty-eight patients who received at least one cycle of eribulin were identified. Most patients were heavily pretreated with a median of 3 (range 1–7) previous chemotherapy lines prior to eribulin. Median patient age was 56 years (range 35–74). At the end of the analysis, 23 patients were alive and two were still treated with eribulin. No hypersensitivity reactions and no toxic deaths were seen. Fatigue grade 3–4 was observed in three patients (6.3%). One patient experienced grade 4 neurotoxicity. Grade 3–4 neutropenia was documented in 18.8%, and three patients were treated for a grade 3 infection. Interestingly, three individuals developed Herpes zoster reactivation. One patient responded to treatment with complete remission, while 33.3% had a partial response. 48% of all patients had a clinical benefit (objective response or stable disease for more than six months).</p><p><b>Conclusions.</b> Eribulin administered outside of a clinical trial in patients with advanced breast cancer was safe and well tolerated. A clinical benefit was seen in half of the cases. No statistically significant differences in objective response or survival were observed between histopathological subgroups.</p></div

DataSheet_1_Expression patterns and prognostic implications of tumor-infiltrating lymphocytes dynamics in early breast cancer patients receiving neoadjuvant therapy: A systematic review and meta-analysis.docx

PurposeHigh levels of tumor-infiltrating lymphocytes (TILs) are associated with better outcomes in early breast cancer and higher pathological response rates to neoadjuvant chemotherapy especially in the triple-negative (TNBC) and HER2+ subtypes. However, the dynamic changes in TILs levels after neoadjuvant treatment (NAT) are less studied. This systematic review and meta-analysis aimed to investigate the patterns and role of TILs dynamics change in early breast cancer patients receiving NAT.MethodsMedline, Embase, Web of Science Core Collection and PubMed Central databases were searched for eligible studies. Data were extracted independently by two researchers and discordances were resolved by a third. Pooled TILs rates pre- & post-treatment (overall and per subtype), pooled rates of ΔTILs and direction of change after NAT as well as correlation of ΔTILs with survival outcomes were generated in the outcome analysis.ResultsOf 2116 identified entries, 34 studies fulfilled the criteria and provided adequate data for the outcomes of interest. A decreased level of TILs was observed after NAT in paired samples across all subtypes. The effect of NAT on TILs was most prominent in TNBC subtype with a substantial change, either increase or decrease, in 79.3% (95% CI 61.7-92.6%) of the patients as well as in HER2+ disease (14.4% increased vs 46.2% decreased). An increase in ΔTILs in TNBC was associated with better disease-free/relapse-free survival in pooled analysis (univariate HR = 0.59, 95% CI: 0.37–0.95, p = 0.03).ConclusionThis meta-analysis illustrates the TILs dynamics during NAT for breast cancer and indicates prognostic implications of ΔTILs in TNBC. The potential clinical utility of the longitudinal assessment of TILs during neoadjuvant therapy warrants further validation.</p

Additional file 6: of Identification and validation of single-sample breast cancer radiosensitivity gene expression predictors

Figure S2. Hierarchical clustering of the top discriminating genes selected in the discovery analysis. Genes are presented as rows, and samples as columns. Colors of the columns represent group after stratification for estrogen receptor (ER) status and radiotherapy (RT), with red representing tumors with later ipsilateral breast tumor recurrence (IBTR, cases). Colors of the rows shows the group in which the gene was selected. Each of the main four clusters were compared with the clusters described by Fredlund et al. and the cluster with the highest association has been marked. (PDF 1308 kb

Additional file 5: of Identification and validation of single-sample breast cancer radiosensitivity gene expression predictors

Figure S1. Selection of top discrimination genes in the Illumina discovery cohort data. Number of genes in the random forest models are plotted against performance of classifying cases and controls, as measured by cross-validated area under the curve (AUC). The analysis was stratified for estrogen receptor (ER) status and radiotherapy (RT) treatment, and with added patients from other strata, based on a biological rationale as described in the text. (ZIP 171 kb

Additional file 1: of Identification and validation of single-sample breast cancer radiosensitivity gene expression predictors

Figure S3. Principle component analysis (PCA) plot of the gene expression data from the targeted panel, with coloring for the biobank center from which the samples were derived. Center 1 and 3 had samples of higher quality RNA and constituted the discovery cohort. Center 2 constituted the validation cohort. (PDF 184 kb

Additional file 2: of Identification and validation of single-sample breast cancer radiosensitivity gene expression predictors

Supplemental methods, results and discussion. (DOCX 91 kb

Additional file 9: of Identification and validation of single-sample breast cancer radiosensitivity gene expression predictors

Table S2. Patient characteristics per cohort, estrogen receptor status and radiotherapy status. (XLSX 20 kb

Additional file 8: of Identification and validation of single-sample breast cancer radiosensitivity gene expression predictors

Figure S4. Correlation of SSP scores with proliferation and immune response. Raw SSP scores are plotted against a proliferation score and an immune score, respectively. SSP scores are calculated based on the four different models developed stratified for estrogen receptor (ER) status and radiotherapy (RT) (ER+RT+, ER+RT-, ER-RT+, ER-RT-). Pearson correlation values and p-value from a linear model with test for zero slope are plotted together with the linear model fit. (PDF 1160 kb

Additional file 3: of Identification and validation of single-sample breast cancer radiosensitivity gene expression predictors

Table S1. Genes included in the targeted 248-gene panel. (CSV 38 kb

Additional file 7: of Identification and validation of single-sample breast cancer radiosensitivity gene expression predictors

Table S4. Univariable and multivariable Cox -models for the ER+ tumors including variables of “Give RT” vs “No RT” and “Give more treatment”, radiotherapy, and the interaction term between the prediction variable and RT. (XLSX 8 kb