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Background: Prognostic significance of endometrioid epithelial ovarian cancer (EOC) is controversial. We compared clinical, pathological, and biological features of patients with endometrioid and serous EOC, and assessed the independent effect of histology on outcomes., Methods: We conducted a multicenter retrospective analysis of patients with EOC selected from the French Epidemiological Strategy and Medical Economics OC database between 2011 and 2016. Our main objective was to compare overall survival (OS) in endometrioid and serous tumors of all grades. Our second objectives were progression-free survival (PFS) and prognostic features., Results: Out of 10,263 patients included, 3180 cases with a confirmed diagnosis of serous (N = 2854) or endometrioid (N = 326) EOC were selected. Patients with endometrioid histology were younger, more often diagnosed at an early stage, with lower-grade tumors, more frequently dMMR/MSI-high, and presented more personal/familial histories of Lynch syndrome-associated cancers. BRCA1/2 mutations were more frequently identified in the serous population. Endometrioid patients were less likely to receive chemotherapy, with less bevacizumab. After median follow-up of 51.7 months (95CI[50.1-53.6]), five-year OS rate was 81% (95CI[74-85]) in the endometrioid subgroup vs. 55% (95CI[53-57] in the serous subset (p < 0.001, log-rank test). In multivariate analyses including [age, ECOG-PS, FIGO, grade, and histology], the endometrioid subtype was independently associated with better OS (HR = 0.38, 95CI[0.20-0.70], p= 0.002) and PFS (HR = 0.53, 95CI[0.37-0.75], p < 0.001)., Conclusions: Clinicopathological features at diagnosis are not the same for endometrioid and serous EOC. Endometrioid histology is an independent prognosis factor in EOC. These observations suggest the endometrioid population requires dedicated clinical trials and management., Competing Interests: Declaration of Competing Interest All the authors declare that they have no conflicts of interest to disclose related to this work., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Treatment strategies for metastatic breast cancer (MBC) have made great strides over the past 10 years. Real-world data allow us to evaluate the actual benefit of new treatments. ESME (Epidemio-Strategy-Medico-Economical)-MBC, a nationwide observational cohort (NCT03275311), gathers data of all consecutive MBC patients who initiated their treatment in 18 French Cancer Centres since 2008., Patients and Methods: We evaluated overall survival (OS) in the whole cohort (N = 20 446) and among subtypes: hormone receptor positive, human epidermal growth factor 2 negative (HR+/HER2-; N = 13 590), HER2+ (N = 3919), and triple-negative breast cancer (TNBC; N = 2937). We performed multivariable analyses including year of MBC diagnosis as one of the covariates, to assess the potential OS improvement over time, and we described exposure to newly released drugs at any time during MBC history by year of diagnosis (YOD)., Results: The median follow-up of the whole cohort was 65.5 months (95% CI 64.6-66.7). Year of metastatic diagnosis appears as a strong independent prognostic factor for OS [Year 2016 HR 0.89 (95% CI 0.82-0.97); P = 0.009, using 2008 as reference]. This effect is driven by the HER2+ subcohort, where it is dramatic [Year 2016 HR 0.52 (95% CI 0.42-0.66); P < 0.001, using 2008 as reference]. YOD had, however, no sustained impact on OS among patients with TNBC [Year 2016 HR 0.93 (95% CI 0.77-1.11); P = 0.41, using 2008 as reference] nor among those with HR+/HER2- MBC [Year 2016 HR 1.02 (95% CI 0.91-1.13); P = 0.41, using 2008 as reference]. While exposure to newly released anti-HER2 therapies appeared very high (e.g. >70% of patients received pertuzumab from 2016 onwards), use of everolimus or eribulin was recorded in less than one-third of HR+/HER2- and TNBC cohorts, respectively, whatever YOD., Conclusion: OS has dramatically improved among HER2+ MBC patients, probably in association with the release of several major HER2-directed therapies, whose penetrance was high. This trend was not observed in the other subtypes, but the impact of CDK4/6 inhibitors cannot yet be assessed., Competing Interests: Disclosure AG reports nonfinancial support from AstraZeneca, Roche, Pfizer, and Novartis, outside the submitted work. WJ reports grants, personal fees, and nonfinancial support from Astra Zeneca; personal fees and nonfinancial support from Eisai, Novartis, Roche, Pfizer, Eli Lilly, and Chugai; personal fees from MSD and BMS, outside the submitted work. P-HC reports grants and nonfinancial support from Roche and Pfizer, outside the submitted work. FC reports grants and personal fees from Merck Serono and BMS; nonfinancial support from Lilly; personal fees and nonfinancial support from Roche; and grants from AstraZeneca, outside the submitted work. ED reports personal fees and nonfinancial support from Novartis and Pfizer; and nonfinancial support from Lilly, outside the submitted work. TB reports personal fees and nonfinancial support from Roche and AstraZeneca; grants, personal fees, and nonfinancial support from Novartis and Pfizer; and personal fees from Seattle Genetics, outside the submitted work. DP reports personal fees from Laboratoire Roche, Pierre Fabre, Novartis, BMS, Eli-Lilly, Ipsen, MSD; personal fees and nonfinancial support from Laboratoire AstraZeneca; grants from Laboratoire MDS Avenir outside the submitted work and Laboratoire Roche (ESME program). SD reports grants and nonfinancial support from Pfizer, AstraZeneca, and Roche Genentech; grants from Novartis, Lilly, Puma, Myriad, Orion, Amgen, Sanofi, Genomic Health, GE, Servier, MSD, BMS, and Pierre Fabre, outside the submitted work. All remaining authors have nothing to disclose., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Leptomeningeal metastasis (LM) is a rare complication of metastatic breast cancer (MBC), with high morbidity/mortality rates. Our study aimed to describe the largest-to-date real-life population of MBC patients treated with intrathecal (IT) therapy and to evaluate prognostic models., Methods: The Epidemiological Strategy and Medical Economics (ESME) MBC database (NCT03275311) includes all consecutive patients who have initiated treatment for MBC since 2008. Overall survival (OS) of patients treated with IT therapy was estimated using the Kaplan-Meier method. Prognostic models were constructed using Cox proportional hazards models. Performance was evaluated using C-index and calibration plots., Results: Of the 22 266 patients included in the database between 2008 and 2016, 312 received IT therapy and were selected for our analysis. Compared with non-IT-treated patients, IT-treated patients were younger at MBC relapse (median age: 52 years versus 61 years) and more often had lobular histology (23.4% versus 12.7%) or triple-negative subtype (24.7% versus 13.3%) (all P < 0.001). Median OS was 4.5 months [95% confidence interval (CI) 3.8-5.6] and 1-year survival rate was 25.6%. Significant prognostic factors associated with poorer outcome on multivariable analysis were triple-negative subtype (hazard ratio 1.81, 95% CI 1.32-2.47), treatment line ≥3 (hazard ratio 1.88, 95% CI 1.30-2.73), ≥3 other metastatic sites (hazard ratio 1.33, 95% CI 1.01-1.74) and IT cytarabine or thiotepa versus methotrexate (hazard ratio 1.68, 95% CI 1.28-2.22), while concomitant systemic therapy was associated with better OS (hazard ratio 0.47, 95% CI 0.35-0.62) (all P < 0.001). We validated two previously published prognostic scores, the Curie score and the Breast-graded prognostic assessment, both with C-index of 0.57., Conclusions: MBC patients with LM treated with IT therapy have a poor prognosis. We could identify a subgroup of patients with better prognosis, when concomitant systemic therapy and IT methotrexate were used., Competing Interests: Disclosure MCapone reports personal fees (consulting, advisory) from Lilly, Novartis, GT1, Daiichi Sankyo and fees to the institution from AstraZeneca, Sanofi, Servier and AbbVie, outside the submitted work. All other authors have declared no conflicts of interest., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Expression of hormone receptor (HR) for estrogens (ER) and progesterone (PR) and HER2 remains the cornerstone to define the therapeutic strategy for breast cancer patients. We aimed to compare phenotypic profiles between matched primary and metastatic breast cancer (MBC) in the ESME database, a National real-life multicenter cohort of MBC patients. Patients with results available on both primary tumour and metastatic disease within 6 months of MBC diagnosis and before any tumour progression were eligible for the main analysis. Among the 16,703 patients included in the database, 1677 (10.0%) had available biopsy results at MBC diagnosis and on matched primary tumour. The change rate of either HR or HER2 was 27.0%. Global HR status changed (from positive = either ER or PR positive, to negative = both negative; and reverse) in 14.2% of the cases (expression loss in 72.5% and gain in 27.5%). HER2 status changed in 7.8% (amplification loss in 45.2%). The discordance rate appeared similar across different biopsy sites. Metastasis to bone, HER2+ and RH+/HER2- subtypes and previous adjuvant endocrine therapy, but not relapse interval were associated with an HR discordance in multivariable analysis. Loss of HR status was significantly associated with a risk of death (HR adjusted = 1.51, p = 0.002) while gain of HR and HER2 discordance was not. In conclusion, discordance of HR and HER2 expression between primary and metastatic breast cancer cannot be neglected. In addition, HR loss is associated with worse survival. Sampling metastatic sites is essential for treatment adjustment.

Background: High Body mass index (BMI) is a risk factor for breast cancer among postmenopausal women and an adverse prognostic factor in early-stage. Little is known about its impact on clinical outcomes in patients with metastatic breast cancer (MBC)., Methods: The National ESME-MBC observational cohort includes all consecutive patients newly diagnosed with MBC between Jan 2008 and Dec 2016 in the 18 French comprehensive cancer centers., Results: Of 22 463 patients in ESME-MBC, 12 999 women had BMI data available at MBC diagnosis. Median BMI was 24.9 kg/m 2 (range 12.1-66.5); 20% of women were obese and 5% underweight. Obesity was associated with more de novo MBC, while underweight patients had more aggressive cancer features. Median overall survival (OS) of the BMI cohort was 47.4 months (95% CI [46.2-48.5]) (median follow-up: 48.6 months). Underweight was independently associated with a worse OS (median OS 33 months; HR 1.14, 95%CI, 1.02-1.27) and first line progression-free survival (HR, 1.11; 95%CI, 1.01; 1.22), while overweight or obesity had no effect., Conclusion: Overweight and obesity are not associated with poorer outcomes in women with metastatic disease, while underweight appears as an independent adverse prognostic factor., Competing Interests: Declaration of Competing interest V.D reports advisory boards from Roche, Genentech, Lilly, Pfizer, Astra Zeneca, MSD, Daiichi Sankyo and Seattle Genetics. PE-H reports research funding from Pfizer, Novartis E.B receive honoraria or consultation fees: AstraZeneca, BMS, Celgene, Clinigen, G1 Therapeutics, Hospira, Janssen, Mylan, OBI Pharma, Pfizer, Puma, Roche, Samsung; Receipt of grants/research supports: Amgen, HalioDX (Qiagen/Ipsogen), TEVA (Cephalon); Travel support: AstraZeneca, Novartis, Pfizer, Pierre Fabre, Roche, Sandoz. A.G reports travel expenses, accommodation and registration meeting from Astra Zeneca, Roche, Pfizer, Novartis. P.C reports grants form Pfizer and Novartis, personal fees from Pfizer and Lilly, non-financial support from Pfizer. S.D. reports institutional fees and non-financial support from Roche/Genentech; grants, institutional fees and nonfinancial support from Pfizer; institutional fees and nonfinancial support from Puma; grants, institutional fees and non-financial support from AstraZeneca; grants, institutional fees and non-financial support from Novartis; institutional fees and non-financial support from Amgen. E.D reports travel expenses from Pfizer, Novartis and Amgen and boards from Novartis and Pfizer. The other authors declare that they have no conflict of interest to disclose., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background and Aims: Because of its low prevalence, metastatic breast cancer (MBC) in males is managed based on clinical experience with women. Using a real-life database, we aim to provide a comprehensive analysis of male MBC characteristics, management and outcome., Methods: The Epidemiological Strategy and Medical Economics Data Platform collected data for all men and women ⩾18 years with MBC in 18 participating French Comprehensive Cancer Centers from January 2008 to November 2016. Demographic, clinical, and pathological characteristics were retrieved, as was treatment modality. Men were matched 1:1 to women with similar characteristics., Results: Of 16,701 evaluable patients, 149 (0.89%) men were identified. These men were older (median age 69 years) and predominantly had hormone receptor HR+/HER2- disease (78.3%). Median overall survival (OS) was 41.8 months [95% confidence interval (CI: 26.9-49.7)] and similar to women. Median progression-free survival (PFS) with first-line therapy was 9.3 months [95% CI (7.4-11.5)]. In the HR+/HER2- subpopulation, endocrine therapy (ET) alone was the frontline treatment for 43% of patients, including antiestrogens ( n  = 19), aromatase inhibitors ( n  = 15) with luteinizing hormone-releasing hormone (LHRH) analogs ( n  = 3), and various sequential treatments. Median PFS achieved by frontline ET alone was similar in men [9.8 months, 95% CI (6.9-17.4)] and in women [13 months, 95% CI (8.4-30.9)] ( p  = 0.80). PFS was similar for HR+/HER2- men receiving upfront ET or chemotherapy: 9.8 months [95% CI (6.9-17.4)] versus 9.5 months [95% CI (7.4-11.7)] ( p  = 0.22), respectively., Conclusion: MBC management in men and women leads to similar outcomes, especially in HR+/HER2- patients for whom ET should also be a cornerstone. Unsolved questions remain and successfully recruiting trials for men are still lacking., Competing Interests: Conflict of interest statement: The authors declare that there is no conflict of interest., (© The Author(s), 2020.)

Introduction: Patients with metastatic breast cancer (MBC) often require inpatient palliative care (IPC). However, mounting evidence suggests age-related disparities in palliative care delivery. This study aimed to assess the cumulative incidence function (CIF) of IPC delivery, as well as the influence of age., Methods: The national ESME (Epidemio-Strategy-Medical-Economical)-MBC cohort includes consecutive MBC patients treated in 18 French Comprehensive Cancer Centres. ICD-10 palliative care coding was used for IPC identification., Results: Our analysis included 12,375 patients, 5093 (41.2%) of whom were aged 65 or over. The median follow-up was 41.5 months (95% confidence interval [CI], 40.5-42.5). The CIF of IPC was 10.3% (95% CI, 10.2-10.4) and 24.8% (95% CI, 24.7-24.8) at 2 and 8 years, respectively. At 2 years, among triple-negative patients, young patients (<65 yo) had a higher CIF of IPC than older patients after adjusting for cancer characteristics, centre and period (65+/<65: β = -0.05; 95% CI, -0.08 to -0.01). Among other tumour sub-types, older patients received short-term IPC more frequently than young patients (65+/<65: β = 0.02; 95% CI, 0.01 to 0.03). At 8 years, outside large centres, IPC was delivered less frequently to older patients adjusted to cancer characteristics and period (65+/<65: β = -0.03; 95% CI, -0.06 to -0.01)., Conclusion: We found a relatively low CIF of IPC and that age influenced IPC delivery. Young triple-negative and older non-triple-negative patients needed more short-term IPCs. Older patients diagnosed outside large centres received less long-term IPC. These findings highlight the need for a wider implementation of IPC facilities and for more age-specific interventions., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: The impact of locoregional treatment (LRT) on overall survival (OS) in de novo metastatic breast cancer (dnMBC) is still under debate, with very few data available regarding exclusive radiotherapy (ERT) as a therapeutic modality., Methods: We evaluated the impact of ERT, exclusive surgery, or a combination of surgery plus radiotherapy (bimodality therapy, BMT) on survival outcomes in a national real-life dnMBC cohort. The primary and secondary end points were OS and progression free survival (PFS) according to LRT (ERT, exclusive surgery, BMT) and no LRT. Sensitivity analyses were performed using propensity score matched analyses., Results: From 2008 to 2014, 4507 dnMBC patients were identified. Only patients alive and free from progression under systemic therapy at least 1 year after diagnosis were included (n = 1965). Forty-five percent of patients (891/1965) underwent LRT: 41.1% (n = 366) ERT, 13.7% (n = 122) exclusive surgery, and 45.2% (n = 403) BMT. OS adjusted for major prognostic factors was significantly longer in the ERT and BMT group compared with no-LRT group, but not exclusive surgery (hazard ratio (HR) = 0.63, 95% confidence interval (CI) [0.49, 0.80], p < 0.001, HR = 0.61, 95%CI [0.47, 0.78], p < 0.001 and HR = 0.87, 95%CI [0.61, 1.26], p = 0.466 respectively). Results were similar after matching on a propensity score. ERT, surgery and BMT were all associated with a significantly better PFS in multivariable analysis., Conclusion: ERT was significantly associated with better OS in dnMBC, in the same magnitude as BMT, compared with no-LRT. However, even with statistical models adjusted for known prognostic factors and propensity score analysis, selection biases cannot be eliminated from observational studies., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Aim: Real-world data inform the outcome comparisons and help the development of new therapeutic strategies. To this end, we aimed to describe the full characteristics and outcomes in the Epidemiological Strategy and Medical Economics (ESME) cohort, a large national contemporary observational database of patients with metastatic breast cancer (MBC)., Methods: Women aged ≥18 years with newly diagnosed MBC and who initiated MBC treatment between January 2008 and December 2016 in one of the 18 French Comprehensive Cancer Centers (N = 22,109) were included. We assessed the full patients' characteristics, first-line treatments, overall survival (OS) and first-line progression-free survival, as well as updated prognostic factors in the whole cohort and among the 3 major subtypes: hormone receptor positive and HER2-negative (HR+/HER2-, n = 13,656), HER2-positive (HER2+, n = 4017) and triple-negative (n = 2963) tumours., Results: The median OS of the whole cohort was 39.5 months (95% confidence interval [CI], 38.7-40.3). Five-year OS was 33.8%. OS differed significantly between the 3 subtypes (p < 0.0001) with a median OS of 43.3 (95% CI, 42.5-44.5) in HR+/HER2-; 50.1 (95% CI, 47.6-53.1) in HER2+; and 14.8 months (95% CI, 14.1-15.5) in triple-negative subgroups, respectively. Beyond performance status, the following variables had a constant significant negative prognostic impact on OS in the whole cohort and among subtypes: older age at diagnosis of metastases (except for the triple-negative subtype), metastasis-free interval between 6 and 24 months, presence of visceral metastases and number of metastatic sites ≥ 3., Conclusions: The ESME program represents a unique large-scale real-life cohort on MBC. This study highlights important situations of high medical need within MBC patients. DATABASE REGISTRATION: clinicaltrials.gov Identifier NCT032753., Competing Interests: Conflict of interest statement S.D. reports personal fees and non-financial support from Roche/Genentech; grants, personal fees and non-financial support from Pfizer; personal fees and non-financial support from Puma; grants, personal fees and non-financial support from AstraZeneca; grants, personal fees and non-financial support from Novartis; personal fees and non-financial support from Amgen. T.B. reports grants, personal fees and non-financial support from Novartis, Pfizer and AstraZeneca; personal fees from Seattle Genetics and personal fees and non-financial support from Roche. E.B. reports personal fees from Pfizer, Roche, Mylan, BMS, Clinigen, TLC Pharma Chem, G1 Therapeutics and Samsung and non-financial support from Roche, Pierre Fabre, Novartis, AstraZeneca and Pfizer. W.J. reports personal fees and non-financial support from Eisai, Novartis, Roche, Pfizer and Lilly; grants, personal fees and non-financial support from AstraZeneca; personal fees from MSD; non-financial support from Chugai. M.-A.M.-R. reports other from Novartis, Lilly, Pfizer, Roche, Pierre Fabre and MSD, outside the submitted work. F.D. reports boards from Novartis, Lilly, Pfizer and AstraZeneca. C.L-P. reports non-financial support from Novartis, Roche, Pfizer, AstraZeneca and Fabre. C.C. reports grants from Pfizer, Roche, MSD, AstraZeneca, Eisai and Daiichi. A.G. reports non-financial support from Roche, Novartis, AstraZeneca and Pfizer. M.R. reports other from Roche, Astra Zeneca, MSD, Pfizer, Daiichi Sankyo and Lilly. D.P. reports personal fees from Roche; personal fees and non-financial support from AstraZeneca; and grants from MSD, outside the submitted work. The other authors declare that they have no conflict of interest to disclose., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Aim: The aims of the present study were to describe treatment patterns and survival outcomes in patients with central nervous system metastases (CNSM) selected among metastatic breast cancer (MBC) patients included in a retrospective study from the Epidemiological Strategy and Medical Economics (ESME) MBC cohort., Methods: Neurological progression-free survival (NPFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Significant contributors to NPFS were determined using a multivariate Cox proportional hazards model., Results: After a median follow-up of 42.8 months, of 16 701 patients included in the ESME MBC database, CNSM were diagnosed in 24.6% of patients. The most frequent treatments after diagnosis of CNSM were whole-brain radiotherapy (WBRT) (45.2%) and systemic treatment (59.3%). Median OS and NPFS were 7.9 months (95% CI: 7.2-8.4) and 5.5 months (95% CI: 5.2-5.8), respectively. In multivariate analysis, age >70 years (vs <50 years; HR = 1.40; 95% CI: 1.24-1.57), triple-negative tumours (vs HER2-/HR+; HR = 1.87; 95% CI: 1.71-2.06), HER2+/HR-tumours (vs HER2-/HR+; HR = 1.14; 95% CI: 1.02-1.27), ≥3 metastatic sites (vs < 3; HR = 1.32; 95% CI: 1.21-1.43) and ≥3 previous treatment lines (vs < 3; HR = 1.75; 95% CI: 1.56-1.96) were detrimental for NPFS. A time interval between selection and CNSM diagnosis superior to 18 months (vs <9 months; HR = 0.88; 95% CI: 0.78-0.98) was associated with longer NPFS., Conclusions: This study describes current treatment patterns of MBC patients in a "real life" setting. Despite advances in stereotactic radiation therapy, most of the patients still received WBRT. More research is warranted to identify patient subsets for tailored treatment strategies., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Eribulin mesylate (EM) was recently approved for metastatic breast cancer (MBC) chemotherapy (CT) in late lines by the FDA, with debated results in second line. We evaluated outcomes in breast cancer patients receiving EM as second, third and fourth line in a national real-life cohort of 16,703 consecutive MBC patients initiating their first metastatic therapeutic line between 2008 and 2014. Primary and secondary objectives were overall survival (OS) and progression-free survival (PFS). An imbalance was seen for HER2+ tumors and concomitant anti-HER2 targeted therapies use, we thus performed a subanalysis in HER2- patients. PFS and OS were significantly better in EM patients in third and fourth lines, compared to "Other chemotherapies" patients (PFS: 4.14 vs. 3.02 months, p = 0.0010; 3.61 vs. 2.53 months, p = 0.0102, third and fourth-line; OS: 11.27 vs. 7.65 months, p = 0.0001; 10.91 vs. 5.95 months, p < 0.0001, third and fourth-line). No significant difference was reported in second-line (PFS: 5.06 vs. 4.14 months, p = 0.1171; OS: 13.99 vs. 11.66 months, p = 0.151). Among HER2- patients, a significant difference was seen for all lines, including 2nd-line (PFS: 4.57 vs. 3.91 months, p = 0.0379; OS: 14.98 vs. 10.51 months, p = 0.0113). In this large real-world database, HER2-negative MBC patients receiving EM in second or later CT line presented significantly better PFS and OS. This difference disappeared in second line in the overall population, probably because of the imbalance in HER2-targeted treatments use. Our results mirror those of the published randomized trials. The effect of anti-HER2 therapies addition in this setting still needs to be defined., (© 2019 UICC.)

Background: For luminal metastatic breast cancer (MBC), endocrine therapy (ET) is the recommended initial treatment before chemotherapy. Our objective was to evaluate the efficacy of multiple ET lines in a real-life study., Methods: The Breast Cancer Epidemiological Strategy and Medical Economics (ESME) project analysed data from all patients with systemic treatment for MBC initiated between 2008 and 2014 in one of the 18 French Comprehensive Cancer Centres. The primary end-point was the successive progression-free survival (PFS) evaluation., Results: The ESME research programme included 9921 patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2 (HER2) negative (HER2-) MBC. Before any chemotherapy, 4195 (43.4%), 1252 (29.8%) and 279 (6.6%) patients received one, two or three ET ± targeted therapy, respectively. The median PFS for first-, second- and third-line ET ± targeted therapy was 11.5 (95% confidence interval [CI], 10.8-12.1), 5.8 (95% CI, 5.3-6.1) and 5.5 (95% CI, 4.6-6.3) months, respectively. In a multivariate analysis, time from diagnosis to metastatic recurrence (P < 0.0001), presence of symptoms at metastatic relapse (P = 0.01), number of metastatic sites (P = 0.0003) and their localisation (P < 0.0001) were prognostic factors for PFS1. Duration of previous PFS was the only prognostic factor for subsequent PFS (10% threshold). Ten percent of the patients showed long-term response to ET, with a total treatment duration before chemotherapy ≥43.6 months., Conclusions: Median PFS in our HR+/HER2- real-life cohort is similar to median first-line PFS reported in clinical trials, regardless of ET used as second- and third-line treatment. Despite the international consensus on early initiation of ET, the latter is not prescribed in most of the cases. Patients with a low tumour burden may achieve prolonged response on ET., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Aim: Real-life analysis of overall survival (OS) trends among metastatic breast cancer (MBC) patients may help define medical needs and evaluate the impact of public health investments. The present study aimed to evaluate the independent impact of the year of MBC diagnosis on OS in the Epidemio-Strategy-Medical-Economical (ESME)-MBC cohort., Methods: ESME-MBC (NCT03275311) is a French, national, multicentre, observational cohort including 16,702 consecutive newly diagnosed MBC patients (01 January 2008-31 December 2014). Of 16,680 eligible patients, 15,085 had full immunohistochemistry data, allowing classification as hormone receptor-positive and HER2-negative (HR+/HER2-, N = 9907), HER2-positive (HER2+, N = 2861) or triple-negative (HR-/HER2-, N = 2317) subcohorts. Multivariate analyses of OS were conducted among the full ESME cohort and subcohorts., Results: Median OS of the whole cohort was 37.22 months (95% confidence interval [CI], 36.3-38.04). Year of diagnosis was an independent predictor of OS (hazard ratio 0.98 [95% CI, 0.97-1.00], P = .01) together with age, subtype, disease-free interval, visceral metastases and number of organs involved. Median OS of HR+/HER2-, HER2+ and HR-/HER2- subcohorts was, respectively, 42.12 (95% CI, 40.90-43.10), 44.91 (95% CI, 42.51-47.90) and 14.52 (95% CI, 13.70-15.24) months. Year of diagnosis was a strong independent predictor of OS in HER2+ subcohort (hazard ratio 0.91 [95% CI, 0.88-0.94], P < .001), but not in HR+/HER2- nor HR-/HER2- subcohorts (hazard ratio 1.00 [95% CI, 0.98-1.01], P = .80 and 1.00 [95% CI, 0.97-1.02], P = .90, respectively)., Conclusions: The OS of MBC patients has slightly improved over the past decade. However, this effect is confined to HER2+ cases, highlighting the need of new strategies in the other subtypes., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: For hormone receptor-positive (HR+) human epidermal growth factor receptor 2 (HER2-) negative metastatic breast cancer (MBC), international guidelines recommend endocrine therapy as first-line treatment, except in case of 'visceral crisis'. In the latter case, chemotherapy is preferred. Few studies have compared these two strategies. We used the Epidemiological Strategy and Medical Economics (ESME) programme, UNICANCER, a large national observational database (NCT03275311), to address this question., Methods: All patients who initiated treatment for a newly diagnosed HR+ HER2-negative MBC between January 2008 and December 2014 in any of the 18 French Comprehensive Cancer Centers participating to ESME were selected. Patients should be aromatase inhibitor (AI)-sensitive (no previous AI or relapse occurring more than 1 year after last adjuvant AI). Objectives of the study were evaluation of progression-free and overall survival (OS) according to the type of first-line treatment adjusted on main prognostic factors using a propensity score., Results: Six thousand two hundred sixty-five patients were selected: 2733 (43.6%) received endocrine therapy alone, while 3532 (56.4%) received chemotherapy as first-line therapy. Among the latter, 2073 (58.7%) received maintenance endocrine therapy. Median OS was 60.78 months (95% confidence interval [CI], 57.16-64.09) and 49.64 months (95% CI, 47.31-51.64; p < 0.0001) for patients receiving endocrine therapy alone and chemotherapy ± maintenance endocrine therapy, respectively. However, this difference was not significant after adjusting on the propensity score (hazard ratio: 0.943, 95% CI 0.863-1.030, p = 0.19)., Conclusion: In this large retrospective cohort of patients with AI-sensitive metastatic luminal BC, OS was similar, whether first-line treatment was chemotherapy or endocrine therapy. In agreement with international guidelines, endocrine therapy should be the first choice for first-line systemic treatment for MBC in the absence of visceral crisis., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Bevacizumab combined with paclitaxel as first-line chemotherapy for patients with HER2-negative metastatic breast cancer (MBC) has led to mixed results in randomized trials, with an improvement in progression-free survival (PFS) but no statistically significant overall survival (OS) benefit. Real-life data could help in assessing the value of this combination., Patients and Methods: This study aimed to describe the outcome following first-line paclitaxel with or without bevacizumab in the French Epidemiological Strategy and Medical Economics (ESME) database of MBC patients, established in 2014 by Unicancer. The primary and secondary end points were OS and PFS, respectively., Results: From 2008 to 2013, 14 014 MBC patient files were identified, including 10 605 patients with a HER2-negative status. Of these, 3426 received paclitaxel and bevacizumab (2127) or paclitaxel (1299) as first-line chemotherapy. OS adjusted for major prognostic factors was significantly longer in the paclitaxel and bevacizumab group compared with paclitaxel [hazard ratio (HR) 0.672, 95% confidence interval (CI) 0.601-0.752; median survival time 27.7 versus 19.8 months]. Results were consistent in all supportive analyses (using a propensity score for adjustment and as a matching factor for nested case-control analyses) and sensitivity analyses. Similar results were observed for the adjusted PFS, favoring the combination (HR 0.739, 95% CI 0.672-0.813; 8.1 versus 6.4 months)., Conclusions: In this large-scale, real-life setting, patients with HER2-negative MBC who received paclitaxel plus bevacizumab as first-line chemotherapy had a significantly better OS and PFS than those receiving paclitaxel. Despite robust methodology, real-life data are exposed to important potential biases, and therefore, results need to be treated with caution. Our data cannot therefore support extension of current use of bevacizumab in MBC., (© The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Direct or Ni-catalysed electroreductive homocouplings of organic halides and couplings of organic halides with activated olefins are efficiently conducted by constant current electrolyses in an undivided cell in room-temperature ionic liquids as the solvent-electrolyte media.