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Background Metastatic breast cancer (MBC) behaviour differs depending on hormone receptors (HR) and human epidermal growth factor receptor (HER2) statuses. Methods The kinetics of central nervous system (CNS) metastases (CNS metastasis-free survival, CNSM-FS) and subsequent patient’s prognosis (overall survival, OS) according to the molecular subtype were retrospectively assessed in 16703 MBC patients of the ESME nationwide multicentre MBC database (Kaplan–Meier method). Results CNS metastases occurred in 4118 patients (24.6%) (7.2% at MBC diagnosis and 17.5% later during follow-up). Tumours were HER2−/HR+ (45.3%), HER2+/HR+ (14.5%), HER2+/HR− (14.9%) and triple negative (25.4%). Median age at CNS metastasis diagnosis was 58.1 years (range: 22.8–92.0). The median CNSM-FS was 10.8 months (95% CI: 16.5–17.9) among patients who developed CNS metastases. Molecular subtype was independently associated with CNSM-FS (HR = 3.45, 95% CI: 3.18–3.75, triple-negative and HER2−/HR+ tumours). After a 30-month follow-up, median OS after CNS metastasis diagnosis was 7.9 months (95% CI: 7.2–8.4). OS was independently associated with subtypes: median OS was 18.9 months (HR = 0.57, 95% CI: 0.50–0.64) for HER2+/HR+ , 13.1 months (HR = 0.72, 95% CI: 0.65–0.81) for HER2+/HR−, 4.4 months (HR = 1.55, 95% CI: 1.42–1.69) for triple-negative and 7.1 months for HER2−/HR+ patients ( p  <0.0001). Conclusions Tumour molecular subtypes strongly impact incidence, kinetics and prognosis of CNS metastases in MBC patients. Clinical trial registration NCT03275311.

The impact of adjuvant chemotherapy on breast cancer prognosis has been demonstrated in randomized trials, but its impact is unknown in real-world populations. The aim of this study was to evaluate the effect of adjuvant chemotherapy on the survival of breast cancer patients in an unselected population. This prospective cohort study included 32,502 women treated at the Institut Curie between 1981 and 2008 for a first invasive breast cancer without metastasis. The patients were matched based on their propensity score to receive adjuvant chemotherapy. The matching generated a subsample of 9,180 patients with an overlapping propensity score. In the group without chemotherapy, the overall survival (OS) rates at 5 and 10 years of follow-up were 87.6% (95% CI [86.7-88.6]) and 75.0% (95% CI [73.6-76.5]), respectively, versus 92.1% (95% CI [91.3-92.9]) and 81.9% (95% CI [80.6-83.2]), respectively, in the chemotherapy group. Distant disease-free survival (DDFS) was significantly improved in the five first years (absolute benefit of 3.5%). In a multivariate analysis, adjuvant chemotherapy was associated with better OS (HR = 0.75, 95% CI [0.69-0.83], p<0.0001) and DDFS (HR = 0.82, 95% CI [0.75-0.90], p<0.0001). Adjuvant chemotherapy significantly improves OS and DDFS rates in an unselected population, in accordance with previous results reported by randomized trials.

Background Overall survival (OS) is the gold standard endpoint to assess treatment efficacy in cancer clinical trials. In metastatic breast cancer (mBC), progression-free survival (PFS) is commonly used as an intermediate endpoint. Evidence remains scarce regarding the degree of association between PFS and OS. Our study aimed to describe the individual-level association between real-world PFS (rwPFS) and OS according to first-line treatment in female patients with mBC managed in real-world setting for each BC subtype (defined by status for both hormone-receptor [HR] expression and HER2 protein expression/gene amplification). Methods We extracted data from the ESME mBC database (NCT03275311) which gathers deidentified data from consecutive patients managed in 18 French Comprehensive Cancer Centers. Adult women diagnosed with mBC between 2008 and 2017 were included. Endpoints (PFS, OS) were described using the Kaplan–Meier method. Individual-level associations between rwPFS and OS were estimated using the Spearman’s correlation coefficient. Analyses were conducted by tumor subtype. Results 20,033 women were eligible. Median age was 60.0 years. Median follow-up duration was 62.3 months. Median rwPFS ranged from 6.0 months (95% CI 5.8–6.2) for HR-/HER2 − subtype to 13.3 months (36% CI 12.7–14.3) for HR + /HER2 + subtype. Correlation coefficients were highly variable across subtypes and first-line (L1) treatments. Among patients with HR − /HER2 − mBC, correlation coefficients ranged from 0.73 to 0.81, suggesting a strong rwPFS/OS association. For HR + /HER2 + mBC patients, the individual-level associations were weak to strong with coefficients ranging from 0.33 to 0.43 for monotherapy and from 0.67 to 0.78 for combined therapies. Conclusions Our study provides comprehensive information on individual-level association between rwPFS and OS for L1 treatments in mBC women managed in real-life practice. Our results could be used as a basis for future research dedicated to surrogate endpoint candidates.

Purpose: Observational studies using routinely collected data are faced with a number of potential shortcomings that can bias their results. Many methods rely on controlling for measured and unmeasured confounders. In this work, we investigate the use of instrumental variables (IV) and quasi-trial analysis to control for unmeasured confounders in the context of a study based on the retrospective Epidemiological Strategy and Medical Economics (ESME) database, which compared overall survival (OS) with paclitaxel plus bevacizumab or paclitaxel alone as first-line treatment in patients with HER2-negative metastatic breast cancer (MBC).Patients and methods Causal interpretations and estimates can be made from observation data using IV and quasi-trial analysis. Quasi-trial analysis has the same conceptual basis as IV, however, instead of using IV in the analysis, a “superficial” or “pseudo” randomized trial is used in a Cox model. For instance, in a multicenter trial, instead of using the treatment variable, quasi-trial analysis can consider the treatment preference in each center, which can be informative, and then comparisons of results between centers or clinicians can be informative.Results In the original analysis, the OS adjusted for major factors was significantly longer with paclitaxel and bevacizumab than with paclitaxel alone. Using the center-treatment preference as an instrument yielded to concordant results. For the quasi-trial analysis, a Cox model was used, adjusted on all factors initially used. The results consolidate those obtained with a conventional multivariate Cox model. Conclusion: Unmeasured confounding is a major concern in observational studies, and IV or quasi-trial analysis can be helpful to complement analysis of studies of this nature.

Introduction Improvement in overall survival (OS) by locoregional treatment (LRT) of the primary tumor in de novo metastatic breast cancer (MBC) patients remains controversial. Objective The aim of our study was to evaluate the impact of LRT on OS in a large retrospective cohort of de novo MBC patients, with regard to immunohistochemical characteristics and pattern of metastatic dissemination. Methods We conducted a multicentric retrospective study of patients diagnosed with de novo MBC selected from the French Epidemiological Strategy and Medical Economics MBC database (NCT03275311) between 2008 and 2014. Overall, 4276 women were included in the study. LRT comprised either radiotherapy, surgery, or both. Results LRT was used in 40% of patients. Compared with no LRT, patients who received LRT were younger ( p  < 0.0001) and were more likely to have only one metastatic site ( p  < 0.0001) or bone-only metastases ( p  < 0.0001). LRT was associated with a significantly better OS based on landmark multivariate analysis at 1-year (hazard ratio 0.65, 95% confidence interval 0.55–0.76, p  < 0.001). Similar results were observed in all sensitivity analyses, including propensity score matching. In subgroup analysis, LRT was associated with better OS in patients with hormone receptor-positive/human epidermal growth factor receptor 2 (HER2)-negative (61.6 vs. 45.9 months, p  < 0.001) and HER2-positive tumors (77.2 vs. 52.6 months, p  = 0.008), but not in triple-negative tumors (19 vs. 18.6 months, p  = 0.54), and was also associated with a reduction in the risk of death in visceral metastatic patients ( p  < 0.001). Conclusions LRT was associated with a significantly better OS in de novo MBC patients, including patients with visceral involvement at diagnosis; however, LRT did not impact OS in triple-negative MBC.

BackgroundThe efficacy and added benefit of platinum-based chemotherapy (PtCT) for metastatic breast cancer (MBC) remain unclear in patients with and without germline BRCA1 or BRCA2 mutations (gBRCA1/2m and gBRCA1/2wt, respectively).MethodsWe selected from the French national real-world multicentre ESME cohort (2008–2016) all patients with HER2-negative MBC with known gBRCA1/2 status at first-line chemotherapy initiation. Using multivariable Cox models, we compared the outcome (progression-free (PFS) and overall survival (OS)) of first-line PtCT and non-PtCT regimens based on the patients’ gBRCA1/2 status and tumour subtype.ResultsPatients who received PtCT had more aggressive tumour features. In the multivariable analysis, first-line PtCT was associated with better adjusted PFS and OS in gBRCA1/2m carriers (N = 300), compared with non-PtCT (HR 0.54, 95% CI 0.4–0.73, P < 0.001, and HR 0.70, 95% CI 0.49–0.99, P = 0.047, respectively). Conversely, outcomes were similar in gBRCA1/2wt patients (N = 922) treated with PtCT and non-PtCT, whatever the tumour subtype. Landmark analyses at months 3 and 6 post treatment initiation supported these results.ConclusionsIn this pre-PARP inhibitor real-world cohort, PFS and OS were better after PtCT than non-PtCT in patients with gBRCA1/2m, but not in those with gBRCA1/2wt. These results emphasise the need of early gBRCA1/2 testing in patients with MBC.Clinical trial numberNCT03275311.

PurposeThe currently ongoing Epidemiological Strategy and Medical Economics (ESME) research programme aims at centralising real-life data on oncology care for epidemiological research purposes. We draw on results from the metastatic breast cancer (MBC) cohort to illustrate the methodology used for data collection in the ESME research programme.ParticipantsAll consecutive ≥18 years patients with MBC treatment initiated between 2008 and 2014 in one of the 18 French Comprehensive Cancer Centres were selected. Diagnostic, therapeutic and follow-up data (demographics, primary tumour, metastatic disease, treatment patterns and vital status) were collected through the course of the disease. Data collection is updated annually.Finding to dateWith a recruitment target of 30 000 patients with MBC by 2019, we currently screened a total of 45 329 patients, and >16 700 patients with a metastatic disease treatment initiated after 2008 have been selected. 20.7% of patients had an hormone receptor (HR)-negative MBC, 73.7% had a HER2-negative MBC and 13.9% were classified as triple-negative BC (ie, HER2 and HR status both negative). Median follow-up duration from MBC diagnosis was 48.55 months for the whole cohort.Future plansThese real-world data will help standardise the management of MBC and improve patient care. A dozen of ancillary research projects have been conducted and some of them are already accepted for publication or ready to be issued. The ESME research programme is expanding to ovarian cancer and advanced/metastatic lung cancer. Our ultimate goal is to achieve a continuous link to the data of the cohort to the French national Health Data System for centralising data on healthcare reimbursement (drugs, medical procedures), inpatient/outpatient stays and visits in primary/secondary care settings.Trial registration number NCT03275311; Pre-results.

Background/Aim: Vinorelbine is indicated for use in the treatment of MBC as a single agent or in combination but there is little real world data on this molecule and even less on its oral form. We exploited the Unicancer Epidemiology Strategy Medical-Economics (ESME) metastatic breast cancer (MBC) database to investigate current patterns of use of oral vinorelbine (OV), as well as outcomes of patients receiving this drug. Patients and Methods: Data were collected retrospectively from women and men treated for MBC between 2008 and 2014 at one of 18 French Comprehensive Cancer Centres. The efficacy of OV was evaluated in terms of progression-free (PFS) and overall survival (OS) and treatment duration. The population and patterns of OV usage were also described. Results: A total of 1806 patients (11% of the ESME MBC database) were included in this analysis. OV was prescribed as monotherapy (46%) or in combination (29%), especially with capecitabine. mainly in later treatment lines. Median PFS was 3.3 months: 2.9 months for single agent, 3.6 months for combination therapy. Median OS was 40.9 months. Conclusion: Real-world data offer complementary results to the data from traditional clinical trials, but they concern a much larger population. In this ESME MBC cohort, OV was only prescribed to a small subset of MBC patients. OV was mainly given as single agent to patients with heavily pre-treated MBC; less commonly, it was co-administered with capecitabine or anti-HER2, in earlier lines of therapy. PFS was modest but in line with previous reports.

To study the effects of reduced CD4 T cell activity on hepatitis C virus (HCV) genetic heterogeneity, HCV quasi-species complexity and diversification over time were analyzed for 56 human immunodeficiency virus-coinfected patients. Patients were selected retrospectively from the French Seroconverter Cohort (SEROCO) and the French Hemophilia Cohort (HEMOCO) for having stable CD4 cell counts for 3 years. HCV complexity was assessed by single-strand conformation polymorphism analysis of the envelope-coding region (HVR) and the core region at 2 time points 3 years apart. Increased HVR complexity was associated with higher CD4 cell count and HCV genotype 1 infection. Qualitative variation of HVR and core region was not related to CD4 cell count and depended on the initial complexity. Complexity of both regions remained unchanged over 3 years. Among these HCV-HIV-coinfected patients with stable CD4 cell counts, viral genotype and CD4 cell count may have influenced HVR complexity before their inclusion in the study but were not involved in HVR diversification during the 3-year follow-up period.