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Studies have shown that screen detection by national screening programs is independently associated with better prognosis of breast cancer. The aim of this study is to evaluate the association between tumor biology according to the 70-gene signature (70-GS) and survival of patients with screen-detected and interval breast cancers. All Dutch breast cancer patients enrolled in the MINDACT trial (EORTC-10041/BIG3-04) accrued 2007–2011, who participated in the national screening program (biennial screening, ages 50–75) were included (n = 1102). Distant Metastasis-Free Interval (DMFI) was evaluated according to the 70-GS for patients with screen-detected (n = 754) and interval cancers (n = 348). Patients with screen-detected cancers had 8-year DMFI rates of 98.2% for 70-GS ultralow-, 94.6% for low-, and 93.8% for high-risk tumors (p = 0.4). For interval cancers, there was a significantly lower 8-year DMFI rate for patients with 70-GS high-risk tumors (85.2%) compared to low- (92.2%) and ultralow-risk tumors (97.4%, p = 0.0023). Among patients with 70-GS high-risk tumors, a significant difference in 8-year DMFI rate was observed between interval (85.2%, n = 166) versus screen-detected cancers (93.8%, n = 238; p = 0.002) with a HR of 2.3 (95%CI 1.2–4.4, p = 0.010) adjusted for clinical-pathological characteristics and adjuvant systemic treatment. Among patients with 70-GS high-risk tumors, a significant difference in DMFI was observed between screen-detected and interval cancers, suggesting that method of detection is an additional prognostic factor in this subgroup and should be taken into account when deciding on adjuvant treatment strategies.

Background With 8.7 years follow-up, the prospective phase III randomized MINDACT trial (EORTC 10041/BIG3-04) continues to meet its primary objective, i.e. 95.1% (95%CI 93.1-96.6), 5-year distant metastasis-free survival (DMFS) in clinical high (C-High)/genomic low (G-Low) risk patients who did not receive adjuvant chemotherapy (ACT) (Cardoso et al., ASCO 2020). In addition, about half of the MINDACT patients had a low clinical risk (C-Low) defined by pre-specified clinical-pathological characteristics. Here, we evaluated the outcome of this C-Low population stratified by the 70-gene signature (MammaPrint®) (G-Low or G-High) for outcome considering age, and present data on the total G-low population (C-Low and C-High combined). Methods Of 6693 patients enrolled in the MINDACT trial between 2007 and 2011, 3337 were C-Low, characterized as mainly T1, grade 1 or 2, and node negative. We evaluated the pre-specified DMFS, distant metastasis free interval (DMFI), and overall survival (OS) rates at 5 and 8 years in the C-Low population: i) in patients with genomic low risk (C-Low/G-Low, n=2744) who were recommended to receive endocrine therapy only (for 99% HR+), and ii) in C-Low/G-High who received ACT or not following randomization (ITT, n=690, 81% HR+). Exploratory analyses by age, ≤50 and >50, were conducted for ACT vs no ACT received in C-Low/G-High. In parallel we estimated survival rates for all G-low patients if all would have followed the genomic low risk assignment and received no ACT (C-Low/G-Low, and C-High/G-Low randomized to no ACT double weighted, n=4130). We used Kaplan-Meier estimates for time to event endpoints and hazard ratios with 95%CI from Cox-regression models adjusted for stratification factors used for the randomization. Results C-low/G-low patients who were recommended endocrine therapy only (compliance > 79%, based on local guidelines) have excellent 5 and 8 year survival rates for all endpoints (Table 1). The estimated survival rates for all G-Low patients, if all would have followed the genomic low risk assignment and received no ACT, is excellent as well (Table 1), albeit this population includes both C-Low and C-High patients. The survival estimates for C-Low/G-High patients are for all endpoints a few percentage points lower than for the C-Low/G-Low group (Table 1). At 8 years of follow-up, in the relatively small subset of 690 patients with C-Low/G-High tumors assigned to ACT or not by randomization (ITT), a 1.5% (SE ±2.3%) higher DMFS is seen in the ACT group, and a 2.9% (SE ±2.0%) higher DMFI. This suggested benefit is mostly seen in patients under 50 years of age (absolute Δ in DMFS for ACT vs no ACT at 8 years: 5.4% for age ≤50 vs -0.3% for age >50). Conclusion Patients with a 70-gene G-Low risk tumor have an excellent 8 year outcome in the context of C-Low characteristics when recommended for endocrine therapy only, very close to the outcome in the larger group of all G-Low patients regardless of clinical risk. Stratification of C-Low patients in to G-Low and G-high provides meaningful information. The benefit of ACT in C-Low patients with a 70-gene G-High risk tumor needs further confirmation, especially relevant in younger women. Table 1All Patients PopulationPatientsObserved events% at 5 years (95% CI)% at 8 years (95% CI)DMFSC-Low / G-Low274417097.3 (96.6-97.9)94.7 (93.8-95.6)C-Low / G-High5936194.2 (92.0-95.9)91.1 (88.4-93.3)DMFIC-Low / G-Low274410398.5 (97.9-98.9)96.7 (95.9-97.3)C-Low / G-High5934695.8 (93.8-97.2)93.5 (91.0-95.3)OSC-Low / G-Low274412298.2 (97.6-98.7)96.5 (95.7-97.2)C-Low / G-High5934496.8 (94.9-98.0)93.1 (90.5-95.0)Patients G-low (C-Low & C-High)PatientsEstimated events% at 5 years% at 8 yearsDMFSAll G-Low - no ACT413033996.492.8DMFIAll G-Low - no ACT413024497.494.6OSAll G-Low - no ACT413022397.995.7 Citation Format: Laura J van 't Veer, Fatima Cardoso, Coralie Poncet, Josephine Lopes Cardozo, Suzette Delaloge, Jean-Yves Pierga, Peter Vuylsteke, Etienne Brain, Giuseppe Viale, Sherko Kümmel, Isabel T Rubio, Gabriele Zoppoli, Alistair Thompson, Erika Matos, Khalil Zaman, Susan Knox, Florentine Hilbers, Aleksandra Peric, Bart Meulemans, Martine Picccart, Emiel J Th Rutgers. How low is low risk: MINDACT updated outcome and treatment benefit in patients considered clinical low risk and stratified by genomic signature, age and nodal status [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr GS4-11.

International audience; Objectives: Cochlear implants have a 10-year manufacturer's warranty and may remain functional for more than 25 years after implantation. With the increasing number of users, the number of explantations is set to increase in the future. The main objective of the present study was to determine reasons for cochlear explantation in adults and the proportion carried out during the warranty period.Material and methods: A single-centre retrospective multidisciplinary study of cochlear explantation in adults was performed over a 33-month period. Explantation reasons, interval since implantation and warranty application were analysed.Results: 54% of the 71 explantations were for medical reasons, 45% due to failure (35% "hard failure", 10% "soft failure") and 1% could not be classified; 69% were followed by reimplantation. Failure was confirmed before explantation in 66% of cases. Manufacturer warranties were applicable in 70% of explantations for breakdown, for a total of €335,500.Conclusions: This analysis provides decision support for reimplantation and allows better patient information. Follow-up is essential to optimise warranty application and to promote the proper implant use.

Background: The clinical utility of the 70-gene signature (MammaPrint®) to guide chemotherapy use in T1-3N0-1M0 breast cancer was demonstrated in the Microarray in Node-Negative and 1 to 3 Positive Lymph Node Disease May Avoid Chemotherapy (MINDACT) study. One thousand four ninety seven of 3356 (46.2%) enrolled patients with high clinical risk (in accordance with the modified Adjuvant! Online clinical-pathological assessment) had a low-risk 70-gene signature. Using patient-level data from the MINDACT trial, the cost-effectiveness of using the 70-gene signature to guide adjuvant chemotherapy selection for clinical high risk, estrogen receptor positive (ER+), human epidermal growth factor 2 negative (HER2-) patients was analysed. Patients and methods: A hybrid decision tree-Markov model simulated treatment strategies in accordance with the 70-gene signature with clinical assessment versus clinical assessment alone, over a 10-year time horizon. Primary outcomes were quality-adjusted life years (QALYs), country-specific costs and incremental cost-effectiveness ratios (ICERs) for six countries: Belgium, France, Germany, Netherlands, UK and the US. Results: Treatment strategies guided by the 70-gene signature result in more QALYs compared with clinical assessment alone. Costs of the 70-gene signature strategy were lower in five of six countries. This led to dominance of the 70-gene signature in Belgium, France, Germany, Netherlands and the US and to a cost-effective situation in the UK (ICER £22,910/QALY). Annual national cost savings were €4.2M (Belgium), €24.7M (France), €45.1M (Germany), €12.7M (Netherlands) and $244M (US). UK budget increase was £8.4M. Conclusion: Using the 70-gene signature to safely guide chemotherapy de-escalation in clinical high risk patients with ER+/HER2- tumours is cost-effective compared with using clinical assessment alone. Long-term follow-up and outcomes from the MINDACT trial are necessary to address uncertainties in model inputs., SCOPUS: ar.j, info:eu-repo/semantics/published

International audience; A large-scale use of the renewable energy in agriculture has become an optimal way to successfully deal with theissues of sustainability and climate change. Recently, the integration of solar panels on the roof of the green-house gave birth to a new crop production system called photovoltaic greenhouse.In this paper, we investigated the shading effect of theflexible photovoltaic panels, mounted on the green-house roof area in the checkerboard format, on the microclimate and the tomatoes yield during the summer andwinter period. This study was undertaken in a two tomato canarian greenhouses, typical of the southMediterranean region.The results of our study showed that the photovoltaic panels covering 40% roof area of the canary typegreenhouse does not have a significant effect on the climatic parameters. Additionally, during the hot period, thephotovoltaic panels reduced the temperature inside the greenhouse and sometimes falling in the optimum rangefor the tomatoes growth. Furthermore, this occupancy rate of the photovoltaic panels does not have a significanteffect on the overall yield of tomatoes

Introduction: Male breast cancer (BCa) is a rare disease accounting for less than 1% of all breast cancers (BC) and 1% of all cancers in males. The clinical management is largely extrapolated from female BCa. Few studies have examined the genomic landscape of male BCas, with six male BCas included in The Cancer Genome Atlas (TCGA). Familial studies of male BCas have shown genomic changes similar to female BCa, while a larger targeted sequencing study of 59 male breast cancers identified recurrent mutations affecting PIK3CA and GATA3. To date, there is still limited information regarding the genomic landscape of male BCas; particularly in the context of identifying targeted treatments. To reveal genomic changes that characterize male BCas in the context of known cancer driver genes linked to prognosis and targeted agents, we performed a targeted sequencing study on 248 male BCas from the International Male Breast Cancer Program. Methods: 248 primary M0, ER+ve, HER2-ve male BCas enrolled in the Part 1 (retrospective joint analysis) International Male Breast Cancer Program of 1483 patients diagnosed between 1990-2010 (Cardoso et al. Annals of Oncology, 2018) were processed for nucleic acid extraction from formalin-fixed paraffin embedded (FFPE) tissues. Using the Thermo Fisher Scientific Oncomine Comprehensive Assay v3 (OCAv3), a validated targeted sequencing panel currently used in the NCI-MATCH trial (NCT02465060), we evaluated mutational and copy number variations (CNVs) of genes that are prognostic or predictive to targeted therapies currently in use in the clinic or late-stage clinical trials. The OCAv3 DNA pan-cancer panel assays 115 genes for determining mutational status (48 full coding and 67 hotspot) as well as copy-number assessment in 43 genes. The OCAv3 uses Ampliseq-based technology linked to the Oncomine NGS workflow to identify actionable mutations and CNVs Results: Of the 248 samples assayed, 216 passed strict quality control parameters (87.1%). Using the Oncomine NGS workflow, actionable mutations at ≥5% variant allele frequency (VAF) were most frequently identified in PIK3CA (29.2%), BRCA2 (11.1%), NF1 (11.6%), indels in TP53 (10.6%), ATR (5.6%), ATRX (5.1%), indel BRCA2 (5.1%), TP53 point mutations (4.6%), MET (4.6%), ATM (4.6%), NOTCH2 (4.6%), CHEK1 (4.2%), FANCI (4.2%), PTEN (3.2%) with a number of additional genes identified at lower frequencies. Gene amplifications were most frequently detected in MYC (24.5%), FGFR1 (14.8%), CCND1 (12%), FGF3 (9.7%), FGF19 (9.7%), MDM2 (6.5%), CDK4 (1.4%), FGFR3, MDM4, ERBB2 (0.9% each), and FLT3, AR, MYCL, CDK6, IGF1R, FGFR4, KRAS, AKT3 and ESR1 (0.5% each). Although the results here describe the mutations and copy-number changes deemed to be actionable, further analysis of all non-actionable somatic mutations and CNVs will be presented and compared to female BCas previously assayed using the same panel. Conclusion: In this targeted sequencing study of the largest series of male BCas to our knowledge, we have revealed that PIK3CA continues to be a frequently altered gene in both male and female BCas. However, there is an enrichment of mutations in genes related to DNA repair in male BCs. Interestingly, while MYC is commonly amplified in female BCa, a higher frequency of amplified cases were seen in male BCas, in contrast to female BCas. Together with our previously generated transcriptional profiling data in this data set, we believe that both common and unique biological processes comprising male and female BCas will ultimately improve their clinical management and move towards the goal of precision medicine. This work has been funded by the Breast Cancer Research Foundation (BCRF). Citation Format: Jane Bayani, Coralie Poncet, Cheryl Crozier, Quang M Trinh, Megan Hopkins, Aime Lambert Uwimana, Tammy Piper, Carrie Cunningham, Monika Sobol, Stefan Aebi, Kim Benstead, Oliver Bogler, Lissandra Dal Lago, Florentine Hilbers, Ingrid Hedenfalk, Larissa Korde, Barbro Linderholm, John Martens, Lavinia Middleton, Melissa Murray, Catherine Kelly, Cecilia Nilsson, Monika Nowaczyk, Stephanie Peeters, Aleksandra Peric, Peggy Porter, Carolien Schröder, Isabel T Rubio, Kathryn J Ruddy, Christi van Asperen, Danielle Van Den Weyngaert, Carolien HM van Deurzen, Elise van Leeuwen-Stok, Joanna Vermeij, Eric Winer, Lincoln D Stein, Sharon H Giordano, Fatima Cardoso, John MS Bartlett. The genomic landscape of male breast cancers using the oncomine comprehensive assay for actionable mutations [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-10-03.

Purpose: To investigate the activity of niraparib in patients with germline-mutated BRCA1/2 (gBRCAm) advanced breast cancer. Patients and Methods: BRAVO was a randomized, open-label phase III trial. Eligible patients had gBRCAm and HER2-negative advanced breast cancer previously treated with ≤2 prior lines of chemotherapy for advanced breast cancer or had relapsed within 12 months of adjuvant chemotherapy, and were randomized 2:1 between niraparib and physician’s choice chemotherapy (PC; monotherapy with eribulin, capecitabine, vinorelbine, or gemcitabine). Patients with hormone receptor–positive tumors had to have received ≥1 line of endocrine therapy and progressed during this treatment in the metastatic setting or relapsed within 1 year of (neo)adjuvant treatment. The primary endpoint was centrally assessed progression-free survival (PFS). Secondary endpoints included overall survival (OS), PFS by local assessment (local-PFS), objective response rate (ORR), and safety. Results: After the pre-planned interim analysis, recruitment was halted on the basis of futility, noting a high degree of discordance between local and central PFS assessment in the PC arm that resulted in informative censoring. At the final analysis (median follow-up, 19.9 months), median centrally assessed PFS was 4.1 months in the niraparib arm (n ¼ 141) versus 3.1 months in the PC arm [n ¼ 74; hazard ratio (HR), 0.96; 95% confidence interval (CI), 0.65–1.44; P ¼ 0.86]. HRs for OS and local-PFS were 0.95 (95% CI, 0.63–1.42) and 0.65 (95% CI, 0.46–0.93), respectively. ORR was 35% (95% CI, 26–45) with niraparib and 31% (95% CI, 19–46) in the PC arm. Conclusions: Informative censoring in the control arm prevented accurate assessment of the trial hypothesis, although there was clear evidence of niraparib’s activity in this patient population., SCOPUS: ar.j, info:eu-repo/semantics/published

Male breast cancer (BCa) is a rare disease accounting for less than 1% of all breast cancers and 1% of all cancers in males. The clinical management is largely extrapolated from female BCa. Several multigene assays are increasingly used to guide clinical treatment decisions in female BCa, however, there are limited data on the utility of these tests in male BCa. Here we present the gene expression results of 381 M0, ER+ve, HER2-ve male BCa patients enrolled in the Part 1 (retrospective analysis) of the International Male Breast Cancer Program. Using a custom NanoString™ panel comprised of the genes from the commercial risk tests Prosigna®, OncotypeDX®, and MammaPrint®, risk scores and intrinsic subtyping data were generated to recapitulate the commercial tests as described by us previously. We also examined the prognostic value of other risk scores such as the Genomic Grade Index (GGI), IHC4-mRNA and our prognostic 95-gene signature. In this sample set of male BCa, we demonstrated prognostic utility on univariate analysis. Across all signatures, patients whose samples were identified as low-risk experienced better outcomes than intermediate-risk, with those classed as high risk experiencing the poorest outcomes. As seen with female BCa, the concordance between tests was poor, with C-index values ranging from 40.3% to 78.2% and Kappa values ranging from 0.17 to 0.58. To our knowledge, this is the largest study of male breast cancers assayed to generate risk scores of the current commercial and academic risk tests demonstrating comparable clinical utility to female BCa., SCOPUS: ar.j, info:eu-repo/semantics/published

Background: We explored, within the EORTC10994 study, the outcomes for patients with molecular apocrine (MA) breast cancer, and defined immunohistochemistry (IHC) as androgen-receptor (AR) positive, oestrogen (ER) and progesterone (PR) negative. We also assessed the concordance between IHC and gene expression arrays (GEA) in the identification of MA cancers. Methods: Centrally assessed biopsies for AR, ER, PR, HER2 and Ki67 by IHC were classified into six subtypes: MA, triple-negative (TN) basal-like, luminal A, luminal B HER2 negative, luminal B HER2 positive and “other”. The two main objectives were the pCR rates and survival outcomes in the overall MA subtype (and further divided by HER2 status) and the remaining five subtypes. Results: IHC subtyping was obtained in 846 eligible patients. Ninety-three (11%) tumours were classified as the MA subtype. Both IHC and GEA data were available for 64 patients. In this subset, IHC concordance was 88.3% in identifying MA tumours compared with GEA. Within the MA subtype, pCR was observed in 33.3% of the patients (95% CI: 29.4–43.9) and the 5-year recurrence-free interval was 59.2% (95% CI: 48.2–68.6). Patients with MA and TN basal-like tumours have lower survival outcomes. Conclusions: Irrespective of their HER2 status, the prognosis for MA tumours remains poor and adjuvant trials evaluating anti-androgens should be considered., SCOPUS: ar.j, info:eu-repo/semantics/published

Introduction: Male breast cancer (MBC) is a rare disease accounting for less than 1% of all breast cancers (BC) and 1% of all cancers in males. The clinical management is largely extrapolated from female BC. Several multigene assays are increasingly used to guide clinical treatment decisions in female BC, however there is little data on the utility of these tests in MBC. Methods: Here we present the gene expression results of 380 M0, ER+ve, HER2-ve MBCs enrolled in the Part 1 (retrospective joint analysis) International Male Breast Cancer Program of 1483 patients diagnosed between 1990-2010 (Cardoso et al. Annals of Oncology, 2018). Using a custom Nanostring™ panel comprised of the genes from the commercial risk tests Prosigna®, OncotypeDx® and Mammaprint®, risk scores and intrinsic subtyping data were generated to recapitulate the commercial tests as described by Bayani and Yao et al (npjBreast Cancer, 2017). Survival outcomes by risk classification were analyzed using Cox models with time-dependent covariates when the proportional hazard assumption was not met and adjusted for clinical and treatment variables. Results: Prosigna-like risk scores identified 99 (26.1%) as low-risk, 159 (41.8%) as intermediate-risk, and 122 (32.1%) as high-risk. Using the TAILORx cut-off (25) for OncotypeDx-like risk of recurrence scoring, 158 (41.6%) were identified as low-risk, while 222 (58.4%) were identified as high-risk. MammaPrint-like results identified 175 (46.1%) as low-risk and 205 (53.9%) as high-risk. Overall, patients classified as high-risk had higher grade, more nodal involvement, larger tumors, and more frequently treated with chemotherapy than low-risk patients. Survival analyses demonstrated clear clinical utility for each test, showing patients at high-risk with poor relapse-free survival (RFS) as compared to patients classified as low-risk: Prosigna-like RFS at 3-years (HR=2.20, 95% CI, 1.28-3.80); Oncotype-like RFS at 3-years (HR=1.92, 95% CI, 1.17-3.17); MammaPrint-like RFS (HR=1.51, 95% CI, 1.00-2.27); with similar findings for distant relapse-free survival (DRFS) and overall survival (OS). Across outcomes and all gene signatures, patients with concordant Low/Low risk classification had better prognosis than those with concordant High/High risk classification. PAM50 intrinsic subtyping identified 147 (38.7%) as Luminal A, 57 (15.0%) as Luminal B, 80 (21.1%) as Her2-enriched and 96 (25.3%) as Basal-like; showing overall 34.5% concordance to clinic-pathological subtyping by central pathology (95% CI, 29.7%-39.5%). Comparison between the tests in the MBC cohort and a comparable cohort of female BC from the Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial processed in the same way will be presented. Conclusion: Common transcriptomic assays designed to assess residual risk, validated in female BC, provide similar information in male BC patients. Not surprisingly, disagreement between test results at the individual patient level was observed. To our knowledge, this is the largest study of MBC assayed to generate risk scores of the current commercial BC tests to demonstrate their clinical utility and their differences and similarity to female BC. This work has been funded by the Breast Cancer Research Foundation (BCRF). Citation Format: Bayani J, Poncet C, Yao CQ, Crozier C, Anouk N, Piper T, Cunningham C, Sobol M, Aebi S, Benstead K, Bogler O, Dal Lago L, Fraser J, Hilbers FH, Hedenfalk I, Korde L, Linderholm B, Martens J, Middleton L, Murray M, Kelly C, Nilsson C, Nowaczyk M, Peeters S, Peric A, Porter P, Schröder C, Rubio IT, Ruddy KJ, van Asperen C, Van Den Weyngaert D, van Deurzen C, van Leeuwen-Stok E, Vermeij J, Winer E, Boutros PC, Giordano SH, Cardoso F, Bartlett JM. Evaluation of multiple transcriptomic gene risk signatures in male breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-19-01.

Studies have shown that screen detection by national screening programs is independently associated with better prognosis of breast cancer. The aim of this study is to evaluate the association between tumor biology according to the 70-gene signature (70-GS) and survival of patients with screen-detected and interval breast cancers.All Dutch breast cancer patients enrolled in the MINDACT trial (EORTC-10041/BIG3-04) accrued 2007-2011, who participated in the national screening program (biennial screening, ages 50-75) were included (n = 1102). Distant Metastasis-Free Interval (DMFI) was evaluated according to the 70-GS for patients with screen-detected (n = 754) and interval cancers (n = 348).Patients with screen-detected cancers had 8-year DMFI rates of 98.2% for 70-GS ultralow-, 94.6% for low-, and 93.8% for high-risk tumors (p = 0.4). For interval cancers, there was a significantly lower 8-year DMFI rate for patients with 70-GS high-risk tumors (85.2%) compared to low- (92.2%) and ultralow-risk tumors (97.4%, p = 0.0023). Among patients with 70-GS high-risk tumors, a significant difference in 8-year DMFI rate was observed between interval (85.2%, n = 166) versus screen-detected cancers (93.8%, n = 238; p = 0.002) with a HR of 2.3 (95%CI 1.2-4.4, p = 0.010) adjusted for clinical-pathological characteristics and adjuvant systemic treatment.Among patients with 70-GS high-risk tumors, a significant difference in DMFI was observed between screen-detected and interval cancers, suggesting that method of detection is an additional prognostic factor in this subgroup and should be taken into account when deciding on adjuvant treatment strategies.

Background: Adjuvant systemic treatments (AST) reduce mortality, but have associated short- and long-term toxicities. Careful selection of patients likely to benefit from AST is needed. We evaluated outcome of low-risk breast cancer patients of the EORTC 10041/BIG 3-04 MINDACT trial who received no AST. Patients and methods: Patients with estrogen receptor-positive, HER2-negative, lymph node-negative tumors ≤2 cm who received no AST were matched 1: 1 to patients with similar tumor characteristics treated with adjuvant endocrine therapy (ET), using propensity score matching and exact matching on age, genomic risk (70-gene signature) and grade. In a post hoc analysis, distant metastasis-free interval (DMFI) and overall survival (OS) were assessed by Kaplan–Meier analysis and hazard ratios (HR) by Cox regression. Cumulative incidences of locoregional recurrence (LRR) and contralateral breast cancer (CBC) were assessed with competing risk analyses. Results: At 8 years, DMFI rates were 94.8% [95% confidence interval (CI) 92.7% to 96.9%] in 509 patients receiving no AST, and 97.3% (95% CI 95.8% to 98.8%) in 509 matched patients who received only ET [absolute difference: 2.5%, HR 0.56 (95% CI 0.30-1.03)]. No statistically significant difference was seen in 8-year OS rates, 95.4% (95% CI 93.5% to 97.4%) in patients receiving no AST and 95.6% (95% CI 93.8% to 97.5%) in patients receiving only ET [absolute difference: 0.2%, HR 0.86 (95% CI 0.53-1.41)]. Cumulative incidence rates of LRR and CBC were 4.7% (95% CI 3.0% to 7.0%) and 4.6% (95% CI 2.9% to 6.9%) in patients receiving no AST versus 1.4% (95% CI 0.6% to 2.9%) and 1.5% (95% CI 0.6% to 3.1%) in patients receiving only ET. Conclusions: In patients with stage I low-risk breast cancer, the effect of ET on DMFI was limited, but overall significantly fewer breast cancer events were observed in patients who received ET, after the relatively short follow-up of 8 years. These benefits and side-effects of ET should be discussed with all patients, even those at a very low risk of distant metastasis.

International audience; Objectifs : Les implants cochléaires bénéficient d’une garantie du fabricant d’une durée de 10 ans et peuvent rester fonctionnels plus de 25 ans après leur implantation. Cependant, du fait de l’augmentation de la file active des patients, le nombre d’explantations va s’accroître dans le futur. L’objectif principal était de déterminer les motifs d’explantations cochléaires chez l’adulte et la part de ces explantations réalisées pendant la période de garantie. Matériel et méthode : Un suivi pluridisciplinaire rétrospectif monocentrique des explantations cochléaires chez l’adulte a été réalisé sur une période de 33 mois. Les motifs d’explantation, les délais depuis l’implantation et l’application des garanties des fabricants ont notamment été analysés. Résultats : Sur 71 explantations, 54 % étaient dues à une raison médicale, 45 % à une panne (dont 35 % de hard failures et 10 % de soft failures) et 1 % n’a pas pu être classifié ; 69 % ont été suivies d’une réimplantation. Les pannes étaient confirmées avant l’explantation dans 66 % des cas. Les garanties des fabricants étaient applicables dans 69 % des explantations pour panne, représentant un montant de 335 500 €. Conclusion : Cette analyse permet une aide à la décision de réimplantation et une meilleure information du patient. Le suivi est indispensable pour appliquer au mieux les garanties des fabricants et favoriser le bon usage de ces implants.

The MINDACT trial showed excellent 5-year distant metastasis-free survival of 94·7% (95% CI 92·5-96·2) in patients with breast cancer of high clinical and low genomic risk who did not receive chemotherapy. We present long-term follow-up results together with an exploratory analysis by age., info:eu-repo/semantics/published

Cochlear and brainstem implants have been included on the list of reimbursable products (LPPR) in France since March of 2009. The implants were initially inscribed for 5 years, after which an application for renewal with the French National Commission for the Evaluation of Medical Devices and Health Technologies (Commission Nationale d’evaluation des dispositifs medicaux et des technologies de sante – CNEDiMTS) was required [Haute Autorite de sante, 2009]. Upon registration to the list of reimbursable products, the companies and the reference centers for cochlear and brainstem implants were asked to set up a post-registration registry called EPIIC. This article reports the evolution in the EPIIC registry of the general indicators for 5051 patients over the five years from 2012–2016.

Assessment of the incidence and results of bilateral cochlear implantation in adults and children in France.Multicenter retrospective study of data in the French national registry of cochlear implantations from January 1st 2012 to December 31st 2016. Functional results from CAP (Category of Auditory Performance) questionnaires and speech audiometry tests, with mono- and di-syllabic word-lists, were compared before and after implantation. Speech audiometry tests were carried out against a noisy background, except before simultaneous implantations.Nine hundred and forty two bilateral cochlear implantations were performed during this period, that is, 16.4% of all cochlear implantations. Five hundred and eighty eight bilateral implantations were performed sequentially. 59% of the bilateral implantations were performed in children. Bilateral implants significantly improved CAP scores in all cases (P0.001). Auditory performance, with the two types of word-list, were significantly improved after simultaneous implantation (P0.01). After sequential implantation, the speech discrimination score, already very good with the first implant, reached 63±26% [0-100] with monosyllabic word lists, and 72±28% [0-100] with dissyllabic words. There were more complications due to surgery in bilateral cases than in the entire population of cochlear recipients (9.1% vs 6.4%, P0.02).Hearing is significantly improved by simultaneous cochlear implantation. For sequential implantation, at one year, when auditory results were already excellent from the first implant, in the bimodal condition CAP scores were significantly improved, although there was no further change in speech audiometry in noise.

This study concerns the results of cochlear implantation in children and adults from French cochlear implantation centers, monitored at one, two and three years by the Cochlear Implant French Registry EPIIC. This multicenter study enrolled 2603 subjects (1667 adults and 936 children) implanted in one ear. The following parameters were studied: hearing overall performances, monosyllabic or dissyllabic word perception, speech intelligibility, self-assessment questionnaire of Cochlear Implant (CI) benefits (Abbreviated profile of Hearing aid Benefit); professional activity and schooling. This study confirms the ceiling effect in adults’ performances after the 1st year and the progressive growth in children's performances. It also shows that the contralateral hearing aid enhances performances compared to the CI alone condition, in all follow-up sessions. The French register of CIs is the only worldwide register of systematic follow-up on a period of three years and more of all adults and children implanted in a country. 137;Supplement 1

Objectives :To analyze the performance of cochlear implants in French patients aged 65 and over, implanted between 2012 and 2016, using data from the French national registry for cochlear implants (EPIIC). Materials and methods : The French national registry incorporates patient data from before implantation and for three years after implantation, stratified in different age groups (18–39, 40–64 years, 65–74 years and > 75 years). Here, we assessed the latter two categories. Hearing was assessed using mono- and disyllabic words in a silent background. The Category of Auditory Performance (CAP) scale was also implemented and subjects took the Abbreviated Profile of Hearing Aid Benefit (Aphab) questionnaire. Results : The population aged over 65 accounted for 38% (n = 1193) of the 3178 adult implanted patients. The performance for mono- and disyllabic words in silence, the CAP scores and the APHAB questionnaire answers for ease of communication, background noise and reverberation were dramatically improved at one year post-implantation (P < 0.0001 for each score) and remained stable between one and three years thereafter. The percentage improvement was similar across all age groups. The scores for loud-noise intolerance did not change after cochlear implantation in any age group. Conclusion : Cochlear implants improve hearing and communication in subjects aged 65 and over, with comparable efficiency to that achieved in younger subjects. Cochlear implantation should thus be proposed whenever hearing aids provide only limited benefit. However, between 2012 and 2016, cochlear implantation was given to less than 1% of the French population aged 65 and over with profound deafness.

This study aims to determine the frequency and causes of cochlear explants with re-implantation (ERI) after 5 years’ follow up of the patients included in the French national EPIIC (étude post-inscription des implants cochléaires) registry tracking patients with cochlear implantation. This multicenter, descriptive prospective study was conducted on 5051 patients enrolled in the EPIIC database between January 2012 and December 2016. Ninety-five patients (1.9%) received a primary implant and an ERI during the study. Of these, four benefitted from two ERIs. The number of ERIs was significantly higher in the pediatric population than among adults. The explantation and reimplantation were performed simultaneously in 86% of cases. The reasons for explantation were: in 46.4% of cases linked to a malfunction of the implant, and in 39.3% of cases for medical or surgical reasons. The number of electrodes inserted was significantly higher after the ERI than after the first implantation. There was just one post-ERI infection for these 95 explanted and re-implanted patients. As well as explantation with reimplantation rarely being necessary, it generally presents no major surgical difficulty and in most cases it allows a better integration than in the first implantation. 137;Supplement 1

Objective Multi-centre study of the National French Registry (EPIIC) of patients with cochlear implants, focusing on infants who were operated-on under the age of 24 months between 2012 and 2016. Patients and methods A total of 615 profoundly deaf infants, who received cochlear implants (CIs) before their second birthday, were included in the registry by different CI centers. Epidemiological, surgical, speech therapy and school, follow-up data were included in the registry, 12, 24, 36 and 48 months thereafter. The following parameters were studied: type of implantation (uni- or bilateral), complications, cause of deafness, category of auditory perception (CAP), Open-set word recognition score (OSW), speech intelligibility rating, lexical comprehension with EVIP (Peabody), communication mode and type of schooling. Bilateral simultaneous CI (BiCI) and unilateral CI (UniCI) groups were compared. Results There were 744 implantations. The explantation-reimplantation rate, within the four-year follow-up, was just 3.6%. Mean implantation age was 16.0 months, and similar in the two groups (BiCI/UniCI). A total of 51% of children had their first implant between 12 and 18 months, and 15% before 12 months. Implantation was unilateral in 52% of cases. Fifty-six percent of the bilateral procedures were sequential, with a mean delay of 16.8 months for the second implantation. The cause of deafness was unknown in 52% of cases. Of the 48% (297/615) of attributed cases, 32% had clear genetic causes. The remaining deafness was due to cytomegalovirus (CMV, 8%), inner-ear malformation (5%) and meningitis (3%). The main complications were from infections (47%) and internal device failure (25%). Four years post-operation, 84% of the UniCI and 75% of BiCl groups had a CAP ≥ 5, and 83% of UniCl and 100% BiCI had OSW ≥ 80%. Furthermore 74% of UniCI and 77% of BiCI communicated orally and 85% of UniCI and 90% of BiCI integrated into mainstream schooling. Conclusion The French Registry of cochlear implants (EPIIC) is the only such national registry in the world. Our analysis illustrates the immediate benefits of, either single or double, cochlear implantation for language, perception skills and schooling.

Evaluate in France the outcomes of cochlear implantation outside the selection criteria, off-label.This is a prospective cohort study including adults and children having received a cochlear implant (CI) in an off-label indication, that is outside the criteria established by the "Haute Autorité de santé (HAS)" in 2012. The data was collected from the "EPIIC" registry on recipients who received CIs in France between 2011 and 2014. Speech audiometry was performed at 60dB preimplantation and after one year of CI use, as well as an evaluation of the scores of the quality of life with the APHAB questionnaire, the scores for CAP and the professional/academic status in pre- and post-implantation conditions. Major and minor complications at surgery have been recorded.In total, 590 patients (447 adults and 143 children) with an off-label indication for CIs were included in this study from the EPIIC registry (11.7% of the whole cohort of EPIIC). For adults, the median percentage of comprehension using monosyllabic word lists was 41% in preimplantation condition versus 53% after one year of CI use (P0.001) and 60% versus 71% in dissyllabic word lists (P0.001). The CAP scores were 5 versus 6 in pre- and post-implantation conditions respectively (P0.001) and the APHAB scores were statistically lower after implantation (P0.001). In the children cohort, the median percentage of comprehension using monosyllabic word lists was 51% in preimplantation condition and 65% after CI (P0.001), and 48% versus 82% (P0.001) for dissyllabic word lists. The CAP scores were 5 versus 7 respectively in pre- and post-CI conditions (P0.001). Thirty-two minor complications (5.4%) and 17 major complications (2.8%) were reported in our panel of off-label indication patients.These results suggest that a revision of the cochlear implantation candidacy criteria is necessary to allow more patients with severe or asymmetric hearing loss to benefit from a CI when there is an impact on quality of life despite the use of an optimal hearing aid.

The occurrence of vertigo after cochlear implantation surgery is one of the most common complications, and often transient. The purpose of this study was to evaluate the occurrence of vertigo after unilateral or bilateral cochlear implantation as well as to identify potential predictive factors.Patients who have undergone cochlear implantation and vestibular assessment pre- and postoperatively were included retrospectively. The presence of vertigo before and after surgery was noted. Postoperative vertigo duration was divided into 3 categories: immediate postoperative (less than 2 months), transient postoperative (between 2 months and 1 year), and persistent postoperative (greater than 1 year). Pre- and postoperative vestibular assessment results (caloric irrigation and VEMP tests) as well as patients' age, operated side, surgical technique for round window access, and characteristics of the electrode array were all analyzed as potential predictive factors of postoperative vertigo.A total of 166 cochlear implants (137 patients) were included in the study, with a mean age of 57.5 ± 16.4 years. Of these, 36% developed postoperative vertigo, of which 19.3% was immediately postoperative. At 1 year postoperatively, 6 cases (3.6%) had persistent disabling vertigo, with 2 cases (1.2%) having no history of vertigo prior to cochlear implantation. Regarding caloric irrigation, 21% of the patients had a vestibular deficiency before surgery, and the same percentage had decreased vestibular responses. At 2 months after cochlear implantation, 31% of the patients exhibited an alteration in their vestibular test results, and 23.5% had experienced immediate postoperative vertigo. None of the factors studied (age, operated side, surgical technique, electrode array characteristics, and vestibular test alteration) correlated with the occurrence of short-term or long-term postoperative vertigo.The occurrence of vertigo after cochlear implantation is difficult to predict by the healthcare team and may develop into an invalidating condition. Each vestibular examination performed routinely only evaluates a specific vestibular organ dysfunction. Therefore, combining several vestibular assessments tests before and after cochlear implantation can increase their sensitivity of predicting the occurrence and eventual persistence of this symptom.

PURPOSE MINDACT demonstrated that 46% of patients with early breast cancer at high clinical but low genomic risk on the basis of MammaPrint may safely avoid adjuvant chemotherapy. A second random assignment (R-C) compared docetaxel-capecitabine with an anthracycline-based regimen. PATIENTS AND METHODS R-C randomly assigned patients 1:1 between standard anthracycline-based regimens, with or without taxanes (control) and experimental docetaxel 75 mg/m2 intravenously plus oral capecitabine 825 mg/m2 two times per day for 14 days (DC) every 3 weeks for 6 cycles. The primary end point was disease-free survival (DFS). Secondary end points included overall survival and safety. RESULTS Of 2,832 patients, 1,301 (45%) were randomly assigned, and 97% complied with R-C assignment. In the control arm, 29.6% only received taxanes (0.5% of N0 patients). DFS events (n = 148) were much less than required (n = 422) as a result of a lower-than-expected accrual and event rate. At 5 years of median follow-up, DFS was not different between DC (n = 652) and control (n = 649; 90.7% [95% CI, 88% to 92.8%] v 88.8% [95% CI, 85.9% to 91.1%]; hazard ratio [HR], 0.83 [95% CI, 0.60 to 1.15]; P = .26). Overall survival (HR, 0.91 [95% CI, 0.54 to 1.53]) and DFS in the clinical high and genomic high-risk subgroup (86.1% v 88.1%; HR, 0.83 [95% CI, 0.58 to 1.21]) were similar in both arms. DC led to more grade 1 neuropathy (27.1% v 11.2%) and more grade 2 hand/foot syndrome (28.5% v 3.3%) and diarrhea (13.7% v 5.8%). Serious cardiac events occurred in 9 patients (control, n = 4; DC, n = 5). Fifty-three patients developed second cancers (control, n = 32; DC, n = 21; leukemia: 2 v 1). Five treatment-related deaths occurred (control, 2 [0.3%]; DC, 3 [0.5%]). CONCLUSION Although underpowered, this second randomization in MINDACT did not show any improvement in outcome or safety with the use of DC compared with anthracycline-based chemotherapy.

Background: The MINDACT trial showed excellent 5-year distant metastasis-free survival (DMFS) of 94·7% (95%CI 92·5-96·2) in clinical high (C-High)/genomic low (G-Low) risk patients who did not receive chemotherapy. Long-term follow-up is presented. Methods: 6693 patients were enrolled 2007 to 2011. We reassessed DMFS rate at 5 years in C-High/G-Low patients not receiving chemotherapy (n=644) (primary analysis), updated DMFS and overall survival in C-High/G-Low patients receiving chemotherapy or not (n=749 and 748, respectively) (secondary analysis), and examined a potential age effect ( 50y) for women with HR+/HER2- disease. Findings: At a median follow-up of 8·7 years, the updated 5-year DMFS rate for C-High/G-Low patients receiving no chemotherapy is 95·1% (95%CI 93·1-96·6), above the predefined non-inferiority boundary of 92%, proving MINDACT as a positive de-escalation trial.The 5-year and 8-year outcome of C-High/G-Low patients show a respective 0·9% (SE ±1·1) 2·6% (SE ±1·6) difference in DMFS for chemotherapy versus no chemotherapy (HR 0·66; 95%CI 0·48-0·92), without differences in overall survival (95·7% vs 94·3%).The same comparisons confined to HR+/HER2- disease (91% of patients) generate different gain estimates from chemotherapy administration for DMFS according to age: 5% (SE ±2·8%) in women ≤50 years versus 0·2% (SE ±2·3%) in women > 50 years. Interpretation: The clinical utility of a low risk 70-gene signature for foregoing adjuvant chemotherapy in the presence of a high clinical risk (and up to 3 positive nodes) remains proven. In C-high/G-low patients > 50 years chemotherapy did not improve outcome across the whole follow-up trajectory. At longer follow-up in younger women, while underpowered, a clinically relevant benefit of about 5% was observed, possibly due to chemotherapy-induced ovarian function suppression, and should be part of informed, shared decision-making. Trial Registration: ClinicalTrials.gov number, NTC00433589; EudraCT number, 2005-002625-31. Funding Statement: Funded by the European Commission Sixth Framework Programme and other grants. Declaration of Interests: None to declare. Ethics Approval Statement: All patients gave written informed consent. The ethics committees of all participating sites approved the study, which involved collaboration of seven member groups under the Breast International Group umbrella.

Additional file 2 Supplementary Table 1. Mean and standard deviation over 40 replicates (in brackets) of selection accuracy (r) and inflation coefficient (b) of EBVs and GEBVs for training scenarios T+ and T-.SD: spawning date; FW: female body weight; SW*: spawn weight (adjusted for FW); EN*: egg number (adjusted for FW); EW: average egg weight; ED: average egg diameter. Supplementary Table 2. Selection accuracy (r) and inflation coefficient (b) of EBVs and GEBVs for training scenarios T1 and T2. SD: spawning date; FW: female body weight; SW*: spawn weight (adjusted for FW); EN*: egg number (adjusted for FW); EW: average egg weight; ED: average egg diameter.

Additional file 1 Supplementary Figure 1. Manhattan plot of QTL detected under GBLUP-based GWAS for female reproduction traits. The red line corresponds to the genome-wide significance threshold at 1% after Bonferroni correction and the blue line corresponds to the chromosome-wide significance threshold at 1% after Bonferroni correction. SD: spawning date; SW: spawn weight; EN: egg number; EW: average egg weight; ED: average egg diameter

International audience; Photovoltaic greenhouses are mixed systems, combining electricity and agricultural production in the same area. Moreover, this type of greenhouse conserves all the properties of a conventional greenhouse, as well as offering the possibility of producing and selling electricity. The aim of the present study is to assess both the impact of the shade caused by the photovoltaic panels on the microclimate and the quality of fruits in the greenhouse. Measurements were carried out in an experimental Canary type greenhouse covered with flexible photovoltaic panels on 10% of its total roof area. Results illustrate that this occupancy rate of the photovoltaic panels arranged in checkerboard pattern does not have a significant effect on the agronomic parameters e.g. height, stem diameter and tomato yield, and climatic parameters under the greenhouse cover. Additionally, the presence of photovoltaic panels has a negative effect on the development of the population of Tuta absoluta.

This abstract was withdrawn by the authors.

This abstract was withdrawn by the authors.

Introduction: Male BC is a rare disease (dx) for which management is extrapolated from trials in female BC. Comprehensive prospective data about QoL in men with BC could inform treatment. The international Male BC Consortium conducted a prospective registry of male BC patients of all stages who newly presented to a participating center between October 2013 and February 2017. A QoL substudy was conducted as part of this registry at most participating sites. Methods: Informed consent for participation in the QoL substudy was requested from new enrollees. Those who consented were asked to complete a survey including the EORTC QLQ-C30 and BR23 (breast cancer specific module), adapted by replacing female-specific items with male-specific sexual activity/function items from the prostate module (PR25). Outcomes were scored according to standard EORTC QLQ procedures on a 0-100 scale (with higher scores on QoL/functioning scales representing better QoL and functioning, and higher scores on symptom scales representing worse symptoms). Forms were analyzed centrally by EORTC. In order to compare to female BC, we used reference data from 2782 mixed age (62% under age 60) women with BC (of whom 1,147 had recurrent or metastatic dx, and 464 had stage 1-2 dx) reported in the EORTC QLQ-C30 Reference Values manual (2008). Results: A total of 557 men were enrolled in EORTC10085, 445 at sites participating in the QoL substudy. Consent forms were received from 422/445 (95%) for the substudy. Baseline survey (required to be completed within 30 days of enrollment) compliance was 85% (359/422). Median age at diagnosis was 67 years. There were 111 men (45%) with node-positive M0/MX dx and 27 men (8%) with M1 dx. Their median global health status score at baseline was 75 (IQR 67-83), higher than that documented historically in female BC (67, with IQR 50-83, in both the 2782 women with mixed stage and the subgroup of 464 with stage 1-2 tumors). The participating men's median social functioning score was 100 (IQR 67-100), also higher than the 83.3 (IQR 67-100) reported in mixed stage female BC patients, though no different than the 100 (IQR 67-100) found in women with stage 1-2 dx. Men's most commonly reported symptoms included fatigue (median score 13.9, IQR 0-33), insomnia (median score 0, IQR 0-33), and pain (median score 0, IQR 0-33), for which women's median scores were 33 (IQR 11-44), 33 (IQR 0-33), and 17 (IQR 0-50) with mixed stage dx, and 22 (IQR 0-33), 33 (IQR 0-33), and 17 (IQR 0-33) with stage 1-2 dx. Men's median sexual activity score was 33.3 (IQR 0-50), with less sexual activity reported by older patients and men with M1 dx. In those who were sexually active, median sexual function score was 83 (IQR 75-92), with no difference by age or stage. Conclusions: QoL and symptom burden in male BC patients appears no worse (and possibly better) than that in female patients. Future analyses of 1- and 5-year surveys from this study will assess the impact of specific treatments on changes in symptoms and QoL over time. These data will be useful in future efforts to tailor treatments and target interventions for male BC. Funding: Breast Cancer Research Foundation, Dutch Pink Ribbon Foundation, Swedish BRO, and EBCC Council. Citation Format: Schroder C, Cardoso F, Dijkstra N, van Leeuwen-Stok E, Linderholm B, Morgenstern D, Van Poznak C, Wolff AC, Poncet C, Gomez HL, Aalders K, Bjelic-Radisic V, Werutsky G, Tryfonidis K, Coens C, Giordano SH, Ruddy KJ. Quality of life (QoL) in male breast cancer (BC): Prospective study of the EORTC10085/TBCRC029/BIG2-07/NABCG International male BC program [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-23-02.

Purpose: Increased insight in tumor biology has revealed that not all young women are at high risk of disease recurrence. Therefore, in some patients extent of treatment could probably be safely scaled down. We aimed to evaluate the risk of breast cancer (BC) relapse according to the 70-gene signature (70-GS) result in relation to young age, in early-stage BC patients enrolled in the MINDACT trial. Patients and Methods: The analyzed population consisted of enrolled BC patients in the MINDACT trial with available clinical (C), as per a modified version of Adjuvant!Online, and genomic (G), according to the 70-GS, risk assessments and known age (n=6693). Patients were categorized in three age groups; 55 years (post-menopausal). Clinicopathological and treatment characteristics as well as gene expression were compared for the different age groups further split by corrected risk groups (C-low/G-low, C-low/G-high, C-high/G-low, C-high/G-high). Subsequently, the 5-year distant metastasis-free survival according to risk category was calculated. Results: The study included 1100 patients 55 years of age (50%). Median age of the young group was 41 (25.8-45.0) years. The young age group had a higher frequency of lymph node involvement (25% vs. 22% and 19%), poorly differentiated tumors (42% vs. 26% and 27%), ER-negative tumors (20% vs. 11% and 11%) and triple negative molecular IHC subtype (16% vs. 9% ad 8%). Median tumor size was the same across the 3 age groups (17mm). Of the 1100 young patients, 61% were C-high while the 70-GS assessed 48% as G-high. Overall, 31% were CL/GL (vs. 43% in other age groups), 9% CL/GH, 21% CH/GL and 40% CH/GH (vs. 24% and 25%). In the discordant risk groups, chemotherapy (CT) allocation when randomized to no chemo occurred in 5% of young women as compared to 3% and 1% in the older age groups. Reason for non-compliance was 50/50 between patient refusal and PI decision. Overall, the 5-year DMFS was 94.1% (95% CI 92.4-95.4) in 55. For the young patients, 5-year DMFS was 98.3% for the CL/GL (96.0-99.3), 97.4% in CL/GH (90.0-99.4), 95.5% in CH/GL (91.6-97.7) and 89.2% in CH/GH (85.6-92.0). In the older two age groups (45-55 and >55), the 5-year DMFS rates were 97.8% (96.5.98.6) and 97.2% (96.2-98.0) for CL/GL, 93.9% (88.8-96.7) and 94.5% (91.0-96.7) for CL/GH, 94.5% (92.0-96.3) and 95.4% (93.5-96.8) for CH/GL and 92.0% (89.2-94.1) and 90.4% (88.0-92.4) for CH/GH, respectively. With 9 events in the Conclusion: The use of the 70-GS reduces the proportion of patients characterized as high risk as compared to traditional clinical risk assessment (48% vs. 61%). Outcome was comparable for the 3 age categories with a very good 5-year DMFS of 95-98% in all GL groups. Performing the 70-GS provides clinically relevant information concerning the prognosis for young early-stage BC patients categorized as CH. These results add important new data to the limited available evidence on genomic expression in young BC patients. Citation Format: Aalders K, Genbrugge E, Poncet C, Kuijer A, Pistilli B, Piccart M, Tryfonidis K, van Dalen T, Cardoso F, van 't Veer L, Rutgers E. Young age and the risk of disease recurrence as assessed by the 70-gene signature – an analysis from the EORTC 10041/BIG 03-04 MINDACT trial [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-07-08.

BACKGROUND: Through the International Male Breast Cancer Program, a prospective registry for male BC was created with the goals of evaluating 1) the clinical and biological features of this disease and 2) assessing feasibility of a prospective therapeutic clinical trial. METHODS: All men, with any stage histologically proven invasive breast cancer, age 3 18 years, and newly presenting at the participating institutions (within 3 months prior) were eligible. Patients were enrolled for 30 months after activation of the first center, through February 2017. Per the study design, if RESULTS: 557 patients were enrolled: 75% in Europe, 20% in United States, 5% in other countries. 6.3% of patients had missing forms. Median age was 67 years (range 26-92). 93% were diagnosed 2010-2017. Among patients with complete data, 79% presented with a breast mass. 88% were M0 and 12% M1. Among M0 patients: 47%, 39%, 2%, and 11% had T1, T2, T3, and T4 disease respectively; 52% were N0. Overall, 98% had ER+ disease and 11% had HER2+ cancer. 14% had grade 1, 56% had grade 2, and 30% had grade 3 tumors. Among 112 men who underwent BRCA1 testing, 1 was positive. Among 118 men who had BRCA2 testing, 18 (15%) were positive. 21% of men had prior or concurrent malignancies, with the following most common sites: prostate, non-melanoma skin, colorectal, and melanoma. The prevalence of previously identified possible risk factors for male breast cancer were: overweight/obesity (72%), former/current smoker (51%), current alcohol 31 drink daily (41%), family history of breast cancer (35%), gynecomastia (16%), history radiation exposure (8%), use of anti-androgens (1%), and use of estrogens (1%). CONCLUSION: Through an international collaborative effort, we were able to prospectively accrue 557 patients to a male breast cancer registry. These results demonstrate feasibility of pursuing a therapeutic clinical trial in men with breast cancer. In addition, this study shows the relatively low uptake of BRCA testing, high rates of concurrent/prior malignancy, and the rates of potentially modifiable risk factors in this patient population. Funding from Breast Cancer Research Foundation, Susan G. Komen, Dutch Pink Ribbon Foundation, Swedish Breast Cancer Association (BRO) and EBCC Council. Citation Format: Giordano SH, Schröder CP, Poncet C, van Leeuwen-Stok E, Linderholm B, Abreu MH, Rubio I, Van Poznak C, Morganstern D, Cameron D, Vleugel MM, Smilde TJ, Bozovic-Spasojevic I, Korde L, Russell NS, den Hoed IDM, Honkoop AH, van der Velden AWG, van 't Riet M, Dijkstra N, Bogler O, Goulioti T, Hilsenbeck S, Ruddy KJ, Wolff A, van Deurzen CHM, Martens J, Bartlett JMS, Aalders K, Tryfonidis K, Cardoso F. Clinical and biological characterization of male breast cancer (BC) EORTC 10085/TBCRC 029/BOOG 2013-02/BIG 2-07: Baseline results from the prospective registry [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-23-01.

Rationale: The 70-gene signature (MammaPrint®, MP) is a prognostic test which guides treatment decisions in patients with early breast cancer. After level 1A evidence for clinical utility of MP has been proven, cost-effectiveness data is important to inform reimbursement. Research objectives: To compare cost-effectiveness of adding MP to clinical risk assessment versus clinical risk assessment alone for the US and EU. Clinical risk was assessed by Adjuvant Online! (AOL) as described in Cardoso et al. NEJM 2016. We used prospective survival data from the large randomized phase 3 trial 'Microarray In Node-negative and 1 to 3 positive lymph node Disease may Avoid ChemoTherapy' (MINDACT). Methods: We used a Markov decision model to estimate the expected costs and outcomes (quality adjusted life years; QALYs) for MP versus AOL in early breast cancer patients from a payers perspective in the US and a societal perspective in the EU over a 5 year time horizon. Five year breast cancer overall- and distant metastasis free survival was calculated based on the MINDACT population (n=6,693). Utility scores were collected by means of the EuroQol-5D in the pilot phase of MINDACT(the first n=800 MINDACT patients). Cost data were for the US based on published insurance claim data, for the EU on published health care- and societal costs. The cost-effectiveness was calculated for: (1) total early stage breast cancer population, (2) clinical high risk population and (3) clinical high risk group in the ER+/HER2- population. Finally, budget impact for a high-low range of different countries was calculated, as the application and costs of chemotherapy can be highly variable between countries. Results: For all groups (1,2,and 3) in the US, using MINDACT survival data and insurance claim data, adding MP to AOL saved costs and gained more QALYs compared to AOL alone (total costs per patient $42,223 vs $45,566 and 4.035 vs 4.031 QALYs respectively). Thus, a small difference in quality adjusted life years (0,0041) was observed, whereas a large difference in costs ($3,342) renders MP a highly cost-effective test (less costly & more effective in 64% of the cases). The largest cost-benefit effect was seen for group 3. The cut-off point for MP being cost-effective in the total population (group 1) is when the chemotherapy costs (and consequences) together are above $30,000. In the US, with approximately 250,000 new breast cancer patients per year, and a cost saving of $3,342, annual budget savings are expected to be $836M. Similar results for the Netherlands (15,000 breast cancer patients per year), reveal a cost difference of $300 per patient, and overall annual budget savings are expected to be $4,5M. Conclusion: Adding MP to clinical risk assessment is highly cost-effective compared to clinical risk assessment alone, based on the MINDACT survival data and US insurance claim data, for all above mentioned groups. When costs for chemotherapy (and consequences) exceed $30,000, MP is cost-effective for the total early breast cancer population. When costs for chemotherapy (and consequences) are below $30,000, the MP is cost-effective for the clinical high risk early breast cancer group. The separate results for EU countries will follow. Citation Format: Retèl VP, Joore MA, van 't Veer LJ, Cardoso F, Piccart MJ, Rutgers EJ, Tryfonidis K, Poncet C, van Harten WH. MammaPrint is cost-effective compared to clinical risk assessment in early stage breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P4-12-01.

The introduction of population-based breast cancer screening and implementation of digital mammography have led to an increased incidence of ductal carcinoma in situ (DCIS) without a decrease in the incidence of advanced breast cancer. This suggests DCIS overdiagnosis exists. We hypothesize that asymptomatic, low-grade DCIS can safely be managed by active surveillance. If progression to invasive breast cancer would still occur, this will be low-grade and hormone receptor positive with excellent survival rates. Also, breast-conserving treatment will still be an option, if no prior radiotherapy has been applied. Management by active surveillance also may save many low-grade DCIS patients intensive treatment. Therefore, we will compare active surveillance with conventional treatment, being either mastectomy, wide local excision (WLE) only, or WLE plus radiotherapy, possibly followed by hormonal therapy for primary low-grade DCIS. For this, we conduct a phase III, open-label, non-inferiority, multi-center, randomized clinical trial sponsored by the European Organization for Research and Treatment of Cancer (EORTC-1401-BCG). The Dutch Centers are coordinated by the Dutch Breast Cancer Research Group (BOOG) (BOOG 2014-04). This trial is developed and implemented in close collaboration with patient advocates. Randomization will be in a 1:1 ratio among one of the following arms: (1) active surveillance or (2) standard treatment per local policy. In total, 1,240 women (≥ 45 years) will be included without prior breast cancer, but with asymptomatic, pure, low-grade DCIS, based on a minimum of tissue harvested by biopsy from calcifications detected by population-based or opportunistic screening. Assuming 25% of randomized women qualified to enroll in the study will drop out or will be excluded from per protocol evaluation, at least 1,240 women need to be randomized to obtain the 930 patients required for the evaluation of the primary endpoint. The same follow-up scheme will be applied in both study arms, i.e. annual mammography for a period of 10 years. The primary end-point is ipsilateral invasive breast tumor-free rate at 10 years. Secondary end-points are among others: overall survival, breast cancer-specific survival, mastectomy rate, patient reported outcomes and cost-effectiveness. Accrual has started in the Netherlands in February 2017 and will start internationally in over 30 centers shortly. Acknowledgements: This trial is funded by Pink Ribbon Netherlands, the Dutch Cancer Society and Dutch Cancer Society/Alpe d'HuZes, and Cancer Research UK. Citation Format: Wesseling J, Elshof LE, Tryfonidis K, Poncet C, Aalders K, van Leeuwen-Stok E, Skinner V, Loo C, Winter-Warnars G, Bleiker E, Retèl V, Pijnappel R, Bijker N, Rutgers E, van Duijnhoven F. Update of the randomized, non-inferiority LORD trial testing safety of active surveillance for women with screen-detected low risk ductal carcinoma in situ (EORTC-1401-BCG/BOOG 2014-04, DCIS) [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr OT3-07-01.

International audience; This study is principally based on predicting the consequences on the microclimate of changing greenhouse design. Several variations on the greenhouse design have been described and examined, i.e. the number of spans and gutter height. Climate investigations were based on numerical simulations using the CFD model and included the dynamic effect of the crop on the flow as well as the subsequent heat and mass exchanges. The results show: (i) that the structural design elements, such as the height of the greenhouse and the number of spans, have significant consequences on climate performance; (ii) that we cannot indefinitely increase the height and the number of spans of greenhouses; (iii) that increasing the volume of the greenhouse raises heat requirements and thus the economic profitability of this kind of investment is debatable.

International audience; Future agriculture systems are concerned by two main challenges for humankind: to produce enough to feed a growing world population, and to produce the share of renewable energies. Among these, biofuels and photovoltaics compete for arable land in food production. Photovoltaic systems can combine with extensive agriculture or livestock; in addition, they can share the solar photon flux with plants providing them with protection. Some years ago, we discussed photovoltaic greenhouses (PVG) and the potential synergies between protected agriculture and photovoltaic systems. We concluded that socio-economic and environmental efficiency could be higher in the combined photovoltaic greenhouse than in the solar or the greenhouse systems independently. We highlighted several R&D areas which would strongly impact short-term profitability of the PVG: firstly, to optimize greenhouse designs to incorporate PV systems; secondly, to develop innovative PV systems capable of intercepting a part of the solar spectrum, and of transmitting the useful wavelengths for crops and lastly, to select the crops and cropping systems adapted to the new constraints. The photovoltaic industry is very dynamic and innovative. In just a few years, many new photovoltaic technologies have evolved, better, more diverse, efficient and cheaper technologies arrive on the market every month. Currently, photovoltaic systems can be embedded in semi-rigid supports and can intercept a part of the solar spectrum. Moreover this intercepted spectrum can be chosen and can range between predefined maximum and minimum limits. Other photovoltaic systems have particles oriented in such a way as to intercept perpendicular beams within a solid angle and transmit the rest. They intercept, for instance, the midday beam in summer and transmit it in winter thus helping to passively control the greenhouse temperature and lengthening the cropping periods in regions with hot summers. The photovoltaic industry is rapidly offering innovations that will shake up the greenhouse agriculture. To conclude, the answer to the initial question will definitely depend on the capacity of agriculture and greenhouse industries to follow the pace of ongoing innovation in the dynamic photovoltaic industry.

Background: The achievement of pCR (breast and axilla) is strongly prognostic for event-free (EFS) and overall survival (OS) in EBC (Cortazar 2014), and modulation of therapy improves long-term outcomes for patients with HER2-positive disease not achieving pCR (Von Minckwitz 2019). We sought to investigate prognostic factors for EFS and OS among patients with and without pCR following neoadjuvant systemic treatment consisting of chemotherapy plus anti-HER2 therapy. Methods: We used individual data from 3,710 patients randomized in 11 neoadjuvant trials for HER2-positive EBC with N≥100 patients enrolled, available data for pCR, EFS, and OS, and follow-up ≥3 years. We assessed baseline clinical tumor size (cT) and clinical nodal status (cN) as prognostic factors using stratified (by trial and treatment) Cox models separately for hormone-receptor (HR)-positive vs. HR-negative disease, and for patients who achieved pCR (pCR+; ypT0/is, ypN0) vs. patients who did not achieve pCR (pCR-). Results: The median follow-up overall was 61.2 months. The table shows hazard ratios and 5-year Kaplan-Meier estimates of OS (5yr OS) according to HR and pCR. Comparable results were observed for EFS. Both cT (1-2 vs. 3-4) and cN (cN- vs. cN+) were independent prognostic factors for OS in most subsets, including in pCR+ patients. Conclusions: These results confirm that patients achieving pCR have far better long-term outcomes than patients who do not, and that traditional poor prognostic features namely tumour size and nodal status remain important even after a pCR, with no clear evidence that the relative impact of unfavourable (cT3-4 or cN+) features is different in patients who achieve a pCR than in those who did not. Key words: neo-adjuvant therapy, HER2-targeted therapy, pathological complete response, prognostic factors, overall survival Funding: German Breast Group HR pCRBaseline cT/cN DeathsPatients5yr OS (%)Hazard ratio* [95% CI]HR+ pCR+cT1-2/cN-521298.6%1.0 (reference)(N= 637)cT3-4/cN-46592.9%0.49 [0.21-1.14]cT1-2/cN+720095.1%0.82 [0.34-1.99]cT3-4/cN+1016094.0%0.40 [0.13-1.25]HR+ pCR-cT1-2/cN-1737796.3%1.0 (reference)(N=1399)cT3-4/cN-2514381.8%0.51 [0.36-0.73]cT1-2/cN+4844888.9%0.71 [0.49-1.03]cT3-4/cN+6443184.9%0.36 [0.23-0.58]HR- pCR+cT1-2/cN-319698.1%1.0 (reference)(N=860)cT3-4/cN-89090.4%0.56 [0.32-0.98]cT1-2/cN+1928092.4%0.49 [0.24-0.98]cT3-4/cN+3029489.5%0.27 [0.12-0.64]HR- pCR-cT1-2/cN-2114083.2%1.0 (reference)(N=814)cT3-4/cN-207871.4%0.46 [0.34-0.64]cT1-2/cN+4225181.6%0.76 [0.53-1.09]cT3-4/cN+11634561.9%0.35 [0.22-0.56]*Hazard ratio cT1-2/cN- vs. higher risk cohorts Citation Format: Sibylle Loibl, Michael Untch, Marc Buyse, André Robidoux, Luca Gianni, Andreas Schneeweiss, Pierfranco Conte, Martine Piccart, Hervé Bonnefoi, Christian Jackisch, Valentina Nekljudova, Joseph Costantino, Pinuccia Valagussa, Colin Neate, Richard Gelber, Coralie Poncet, Pierre Squifflet, Everardo Saad, Dominik Heinzmann, Carsten Denkert, Charles E Geyer, Javier Cortes, Valentina Guarneri, Evandro de Azambuja, David Cameron, Gustavo Ismael, Gunter von Minckwitz, Norman Wolmark, Patricia Cortazar. Pathologic complete response (pCR) and prognosis following neoadjuvant chemotherapy plus anti-HER2 therapy of HER2-positive early breast cancer (EBC) [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-06-02.