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Fertility issues are of great concern for young women undergoing treatment for breast cancer (BC). Fertility preservation (FP) protocols using controlled ovarian stimulation (COS) with letrozole have been widely used with overall good results. However, letrozole cannot be used in every country in this context. This study aimed to assess the efficacy of tamoxifen for COS in women with early BC undergoing FP. This multicentric prospective study included patients aged 18–40, diagnosed with stage I, II and III invasive BC, undergoing tamoxifen-COS before adjuvant or neoadjuvant chemotherapy (NAC). The primary endpoint was the efficacy of tamoxifen-COS protocol evaluated by the number of oocytes collected and vitrified. Secondary endpoints included the time interval before chemotherapy, breast cancer (BC) recurrence rates, and reproductive outcomes. Ninety-five patients were included between 2014 and 2017, aged 31.5 ± 4 years on average. 37.9 % received NAC and 62.1 % received adjuvant chemotherapy. FP procedure was successful in 89.5 % of the cycles. The mean number of collected and vitrified oocytes was 12.8 ± 7.9 and 9.8 ± 6.2, respectively. The mean duration of COS was 10.4 ± 1.9 days. Median time before chemotherapy initiation was 3.6 weeks (IQR 3.1; 4.1) for women receiving NAC. Five-year relapse-free and overall survival rates were in-line with those expected in this population. Twenty-one women had spontaneous full-term pregnancies, while 5 underwent IVF cycles with frozen-thawed oocytes, without pregnancy. Tamoxifen-COS protocols appear to be feasible before adjuvant or NAC treatment in young BC patients and efficient in terms of oocyte yield. • Fertility issues are of great concern for young women undergoing treatment for breast cancer. • In breast cancer (BC) patients, international guidelines advocate for controlled ovarian stimulation (COS) with an aromatase inhibitor (AI) or tamoxifen. • AI are not permitted in this indication in some countries and efficacy of tamoxifen-COS have been less evaluated at the time of initiating the study. • In this observational prospective study, 95 young women underwent tamoxifene-COS before BC chemotherapy and were followed for a period of 5 years. • Tamoxifen-COS protocols are feasible before adjuvant or neoadjuvant chemotherapy in young BC patients, and appear to be efficient in terms of oocyte yield. [ABSTRACT FROM AUTHOR]

Numerical models have been highly successful in simulating global carbon and nutrient cycles in today's ocean, together with observed spatial and temporal patterns of chlorophyll and plankton biomass at the surface. With this success has come some confidence in projecting the century‐scale response to continuing anthropogenic warming. There is also increasing interest in using such models to understand the role of plankton ecosystems in past oceans. However, today's marine environment is the product of billions of years of continual evolution—a process that continues today. In this paper, we address the questions of whether an assumption of species invariance is sufficient, and if not, under what circumstances current model projections might break down. To do this, we first identify the key timescales and questions asked of models. We then review how current marine ecosystem models work and what alternative approaches are available to account for evolution. We argue that for timescales of climate change overlapping with evolutionary timescales, accounting for evolution may to lead to very different projected outcomes regarding the timescales of ecosystem response and associated global biogeochemical cycling. This is particularly the case for past extinction events but may also be true in the future, depending on the eventual degree of anthropogenic disruption. The discipline of building new numerical models that incorporate evolution is also hugely beneficial in itself, as it forces us to question what we know about adaptive evolution, irrespective of its quantitative role in any specific event or environmental changes. Key Points: Marine microbes are key drivers of global biogeochemical cycles and have an immense capacity for evolutionEarth system models do not currently include microbial evolution and thus may miss key feedbacks in a fully coupled systemUnderstanding these feedbacks requires that ecology, evolution, and environment are dynamically represented and linked in models [ABSTRACT FROM AUTHOR]

Objective: Treatment of high-grade serous ovarian carcinomas relies on surgery and chemotherapy, potentially followed by bevacizumab and/or poly (ADP-ribose) polymerase inhibitors (PARPi). The modeled CA-125 ELIMination rate constant K (KELIM) is a pragmatic indicator of tumor primary chemosensitivity. Although it is well established that BRCA mutations are associated with platinum sensitivity, the relationship between BRCA status and KELIM score has yet to be elucidated. This study aimed to evaluate the interactions between BRCA and KELIM, and their respective prognostic values., Methods: We retrospectively collected data from 743 patients with high-grade serous ovarian carcinomas included in a French nationwide registry (NCT03275298) treated with neoadjuvant platinum-based chemotherapy followed by surgery. We analyzed the interactions between BRCA and KELIM, and their impacts on progression-free survival and overall survival., Results: BRCA -mutated (BRCA m) patients had higher standardized KELIM than BRCA -wild type ( BRCA wt) tumors (median 1.16 vs 1.06, respectively; p=0.001). The prognostic value of the KELIM score was independent of BRCA in multivariate analyses. KELIM score and BRCA could be combined to define three prognostic groups: (1) an unfavorable prognostic group with both BRCA wt and unfavorable KELIM (median progression-free survival 12.0 months); (2) an intermediate prognostic group with either BRCA m and unfavorable KELIM, or BRCA wt and favorable KELIM (median progression-free survival of 16.0 and 18.8 months, respectively; HR 0.64 compared with the unfavorable group, p<0.001); and (3) a favorable prognostic group with both BRCA m and favorable KELIM (median progression-free survival 28.8 months; HR 0.37 compared with the unfavorable group, p<0.001)., Conclusions: The KELIM score provides complementary prognostic information with respect to BRCA, and discriminates different prognoses within BRCA m or BRCA wt patients. Patients with both BRCA wt/unfavorable KELIM have a poor prognosis, underscoring the urgent need for novel therapeutic strategies., Competing Interests: Competing interests: J-MC: reports personal fees from AstraZeneca, Roche, Vifor, Clovis, GlaxoSmithKline, and Merck Sharp and Dohme, outside the submitted work. LC: reports non-financial support from Pharmamar and GSK, outside the submitted work. P-EC: reports personal fees from Merck Sharp and Dohme, AstraZeneca, and GlaxoSmithKline, outside the submitted work. AD: reports non-financial support from Monaco Age Oncologie, outside the submitted work. TMR: reports personal fees from Pfizer, AstraZeneca, GlaxoSmithKline, Clovis Oncology, Roche, Merck Sharp and Dohme, Mylan, Tesaro, and Norvartis; grants from Pfizer, Merck Sharp and Dohme, and Seagen; a non-financial advisory role for the French National Cancer Institute, Arcagy, and Unicancer, outside the submitted work. LG: reports personal fees from Viatris, Roche, Merck Sharp and Dohme, Clovis, GlaxoSmithKline, and AstraZeneca, outside the submitted work. FJ: reports personal fees from Amgen, Astellas, AstraZeneca, Byaer, EISAI, GlaxoSmithKline, Ipsen, Janssen, Merck Sharp and Dohme, Novartis, Novocure, Pfizer, Seagen, and Viatris; non-financial support from Astellas, AstraZeneca, Bristol-Meyer Squibb, GlaxoSmithKline, Janssen, Merck Sharp and Dohme, Ipsen, EISAI, and Chugai, outside the submitted work. EL: reports personal fees from Strycker, outside the submitted work. PP: reports personal fees from GlaxoSmithKline, Merck Sharp and Dohme, PharmaMar, and Roche, outside the submitted work. CP: reports personal fees from Roche, GlaxoSmithKline, Pharmamar, and Merck Sharp and Dohme, outside the submitted work. RS: reports grants from AstraZeneca; personal fees from GlaxoSmithKline, EISAI, Seagen, and Novartis; non-financial support from Merck Sharp and Dohme, GlaxoSmithKline, and Novartis, outside the submitted work. IR-C: reports personal fees from Agenus, Amgen, AstraZeneca, Clovis, Deciphera, GlaxoSmithKline, Macrogenics, Merck Sereno, Mersena, Novartis, Oxnea, Roche, Bristol-Meyer Squibb, and Merck Sharp and Dohme, outside the submitted work. MR: reports non-financial support from AstraZeneca; grants from Merck Sharp and Dohme, Daiichi Sankyo, and Bristol-Meyer Squibb; personal fees from AstraZeneca, Immunocore, Merck Sharp and Dohme, and GlaxoSmithKline, outside the submitted work. BY: reports personal fees from Merck Sharp and Dohme, AstraZeneca, GSK-TESARO, Bayer, Roche-Genentech, ECS Progastrine, Novartis, LEK, Amgen, Clovis Oncology, Merck Serono, Bristol-Meyer Squibb, Seagen, Myriad, Menarini, Gilead, and EISAI, outside the submitted work. EB, OB, LB, MCa, MCh, OC, HC, CG, FM, TP, BS, and A-MS have nothing to disclose., (© IGCS and ESGO 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Long-term treatment-related toxicities, such as neurologic and metabolic toxicities, are major issues in breast cancer. We investigated the interest of metabolomic profiling to predict toxicities., Experimental Design: Untargeted high-resolution metabolomic profiles of 992 patients with estrogen receptor (ER)+/HER2- breast cancer from the prospective CANTO cohort were acquired (n = 1935 metabolites). A residual-based modeling strategy with discovery and validation cohorts was used to benchmark machine learning algorithms, taking into account confounding variables., Results: Adaptive Least Absolute Shrinkage and Selection (adaptive LASSO) has a good predictive performance, has limited optimism bias, and allows the selection of metabolites of interest for future translational research. The addition of low-frequency metabolites and nonannotated metabolites increases the predictive power. Metabolomics adds extra performance to clinical variables to predict various neurologic and metabolic toxicity profiles., Conclusions: Untargeted high-resolution metabolomics allows better toxicity prediction by considering environmental exposure, metabolites linked to microbiota, and low-frequency metabolites., (©2024 American Association for Cancer Research.)

Purpose: Socioeconomic status (SES) influences the survival outcomes of patients with early breast cancer (EBC). However, limited research investigates social inequalities in their quality of life (QoL). This study examines the socioeconomic inequalities in QoL after an EBC diagnosis and their time trends., Patients and Methods: We used data from the French prospective multicentric CANTO cohort (ClinicalTrials.gov identifier: NCT01993498), including women with EBC enrolled between 2012 and 2018. QoL was assessed using the European Organisation for Research and Treatment of Cancer QoL Core 30 questionnaire (QLQ-C30). summary score at diagnosis and 1 and 2 years postdiagnosis. We considered three indicators of SES separately: self-reported financial difficulties, household income, and educational level. We first analyzed the trajectories of the QLQ-C30 summary score by SES group. Then, social inequalities in QLQ-C30 summary score and their time trends were quantified using the regression-based slope index of inequality (SII), representing the absolute change in the outcome along socioeconomic gradient extremes. The analyses were adjusted for age at diagnosis, Charlson Comorbidity Index, disease stage, and type of local and systemic treatment., Results: Among the 5,915 included patients with data on QoL at diagnosis and at the 2-year follow-up, social inequalities in QLQ-C30 summary score at baseline were statistically significant for all SES indicators (SII financial difficulties = -7.6 [-8.9; -6.2], SII income = -4.0 [-5.2; -2.8]), SII education = -1.9 [-3.1; -0.7]). These inequalities significantly increased (interaction P < .05) in year 1 and year 2 postdiagnosis, irrespective of prediagnosis health, tumor characteristics, and treatment. Similar results were observed in subgroups defined by menopausal status and type of adjuvant systemic treatment., Conclusion: The magnitude of preexisting inequalities in QoL increased over time after EBC diagnosis, emphasizing the importance of considering social determinants of health during comprehensive cancer care planning.

Introduction: Several studies have shown that emotional competence (EC) impacts cancer adjustment via anxiety and depression symptoms. The objective was to test this model for the quality of life (QoL) of partners: first, the direct effect of partners' EC on their QoL, anxiety and depression symptoms after cancer diagnosis (T1), after chemotherapy (T2) and after radiotherapy (T3); Second, the indirect effects of partners' EC at T1 on their QoL at T2 and T3 through anxiety and depression symptoms., Methods: 192 partners of women with breast cancer completed a questionnaire at T1, T2 and T3 to assess their EC (PEC), anxiety and depression symptoms (HADS) and QoL (Partner-YW-BCI). Partial correlations and regression analyses were performed to test direct and indirect effects of EC on issues., Results: EC at T1 predicted fewer anxiety and depression symptoms at each time and all dimensions of QoL, except for career management and financial difficulties. EC showed different significant indirect effects (i.e. via anxiety or depression symptoms) on all sub-dimensions of QoL, except for financial difficulties, according to the step of care pathway (T2 and T3). Anxiety and depression played a different role in the psychological processes that influence QoL., Conclusion: Findings confirm the importance of taking emotional processes into account in the adjustment of partners, especially regarding their QoL and the support they may provide to patients. It, thus, seems important to integrate EC in future health models and psychosocial interventions focused on partners or caregivers., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

The stoichiometric coupling of carbon to limiting nutrients in marine phytoplankton regulates the magnitude of biological carbon sequestration in the ocean. While clear links between plankton C:N ratios and environmental drivers have been identified, the nature and direction of these links, as well as their underlying physiological and ecological controls, remain uncertain. We show, with a well-constrained mechanistic model of plankton ecophysiology, that while nitrogen availability and temperature emerge as the main drivers of phytoplankton C:N stoichiometry in the North Atlantic, the biological mechanisms involved vary depending on the spatiotemporal scale and region considered. We find that phytoplankton C:N stoichiometry is overall controlled by nitrogen availability below 40° N, predominantly driven by ecoevolutionary shifts in the functional composition of the phytoplankton communities, while phytoplankton stoichiometric plasticity in response to dropping temperatures and increased grazing pressure dominates at higher latitudes. Our findings highlight the potential of "organisms-to-ecosystems" modeling approaches based on mechanistic models of plankton biology accounting for physiology, ecology, and trait evolution to explore and explain complex observational data and ultimately improve the predictions of global ocean models., Competing Interests: The authors declare no competing interest., (Copyright © 2021 the Author(s). Published by PNAS.)

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.)

Introduction: Breast cancer is the most common cancer in women worldwide. The number of childbearing-age women diagnosed with early breast cancer (eBC) is increasing, raising questions over their subsequent fertility., Purpose: The main objective of this study was therefore to assess, in a cohort of eBC patients with pregnancy desire, the rate of live births achieved spontaneously or by assisted reproductive technology., Methods: We conducted an observational, descriptive, retrospective study including patients aged 18-40, treated for eBC at the Institut de Cancérologie de l'Ouest (ICO) Pays de Loire between July 2010 and July 2016, with pregnancy desire. The primary outcome was the rate of live births. Secondary outcomes were overall survival, disease-free survival, time to conception, and spontaneous or assisted pregnancy rate., Results: 61 patients were included, with a live birth rate of 19.7% (12/61). We observed no recurrence or death in women with a pregnancy. Pregnancy started with a median time of 36.4 months after the end of treatment (4.1-51.3 months). All pregnancies in this cohort were achieved spontaneously., Conclusion: The results of our cohort are consistent with previous results showing that spontaneous pregnancy remains possible after treatment for eBC without increasing the risk of recurrence or death., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The end-Cretaceous bolide impact triggered the devastation of marine ecosystems. However, the specific kill mechanism(s) are still debated, and how primary production subsequently recovered remains elusive. We used marine plankton microfossils and eco-evolutionary modeling to determine strategies for survival and recovery, finding that widespread phagotrophy (prey ingestion) was fundamental to plankton surviving the impact and also for the subsequent reestablishment of primary production. Ecological selectivity points to extreme post-impact light inhibition as the principal kill mechanism, with the marine food chain temporarily reset to a bacteria-dominated state. Subsequently, in a sunlit ocean inhabited by only rare survivor grazers but abundant small prey, it was mixotrophic nutrition (autotrophy and heterotrophy) and increasing cell sizes that enabled the eventual reestablishment of marine food webs some 2 million years later., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)

The history of the Earth has been marked by major ecological transitions, driven by metabolic innovation, that radically reshaped the composition of the oceans and atmosphere. The nature and magnitude of the earliest transitions, hundreds of million years before photosynthesis evolved, remain poorly understood. Using a novel ecosystem-planetary model, we find that pre-photosynthetic methane-cycling microbial ecosystems are much less productive than previously thought. In spite of their low productivity, the evolution of methanogenic metabolisms strongly modifies the atmospheric composition, leading to a warmer but less resilient climate. As the abiotic carbon cycle responds, further metabolic evolution (anaerobic methanotrophy) may feed back to the atmosphere and destabilize the climate, triggering a transient global glaciation. Although early metabolic evolution may cause strong climatic instability, a low CO:CH 4 atmospheric ratio emerges as a robust signature of simple methane-cycling ecosystems on a globally reduced planet such as the late Hadean/early Archean Earth.

Models of community assembly have been used to illustrate how the many functionally diverse species that compose plankton food webs can coexist. However, the evolutionary processes leading to the emergence of plankton food webs and their interplay with migratory processes and spatial heterogeneity are yet to be explored. We study the eco-evolutionary dynamics of a modeled plankton community structured in both size and space and physiologically constrained by empirical data. We demonstrate that a complex yet ecologically and evolutionarily stable size-structured food web can emerge from an initial set of two monomorphic phytoplankton and zooplankton populations. We also show that the coupling of spatial heterogeneity and migration results in the emergence of specific biogeographic patterns: (i) the emergence of a source-sink structure of the plankton metacommunities, (ii) changes in size diversity dependent on migratory intensity and on the scale at which diversity is considered (local vs. global), and (iii) the emergence of eco-evolutionary provinces (i.e., a spatial unit characterized by some level of abiotic heterogeneity but of homogenous size composition due to horizontal movements) at spatial scales that increase with the strength of the migratory processes.

Rates of metabolism and population growth are often assumed to decrease universally with increasing organism size. Recent observations have shown, however, that maximum population growth rates among phytoplankton smaller than ∼6 μm in diameter tend to increase with organism size. Here we bring together observations and theory to demonstrate that the observed change in slope is attributable to a trade-off between nutrient uptake and the potential rate of internal metabolism. Specifically, we apply an established model of phytoplankton growth to explore a trade-off between the ability of cells to replenish their internal quota (which increases with size) and their ability to synthesize new biomass (which decreases with size). Contrary to the metabolic theory of ecology, these results demonstrate that rates of resource acquisition (rather than metabolism) provide the primary physiological constraint on the growth rates of some of the smallest and most numerically abundant photosynthetic organisms on Earth.

Most top impact factor ecology journals indicate a preference or requirement for short manuscripts; some state clearly defined word limits, whereas others indicate a preference for more concise papers. Yet evidence from a variety of academic fields indicates that within journals longer papers are both more positively reviewed by referees and more highly cited. We examine the relationship between citations received and manuscript length, number of authors, and number of references cited for papers published in 32 ecology journals between 2009 and 2012. We find that longer papers, those with more authors, and those that cite more references are cited more. Although paper length, author count, and references cited all positively covary, an increase in each independently predicts an increase in citations received, with estimated relationships positive for all the journals we examined. That all three variables covary positively with citations suggests that papers presenting more and a greater diversity of data and ideas are more impactful. We suggest that the imposition of arbitrary manuscript length limits discourages the publication of more impactful studies. We propose that journals abolish arbitrary word or page limits, avoid declining papers (or requiring shortening) on the basis of length alone (irrespective of content), and adopt the philosophy that papers should be as long as they need to be.

The functional and taxonomic biogeography of marine microbial systems reflects the current state of an evolving system. Current models of marine microbial systems and biogeochemical cycles do not reflect this fundamental organizing principle. Here, we investigate the evolutionary adaptive potential of marine microbial systems under environmental change and introduce explicit Darwinian adaptation into an ocean modelling framework, simulating evolving phytoplankton communities in space and time. To this end, we adopt tools from adaptive dynamics theory, evaluating the fitness of invading mutants over annual timescales, replacing the resident if a fitter mutant arises. Using the evolutionary framework, we examine how community assembly, specifically the emergence of phytoplankton cell size diversity, reflects the combined effects of bottom-up and top-down controls. When compared with a species-selection approach, based on the paradigm that "Everything is everywhere, but the environment selects", we show that (i) the selected optimal trait values are similar; (ii) the patterns emerging from the adaptive model are more robust, but (iii) the two methods lead to different predictions in terms of emergent diversity. We demonstrate that explicitly evolutionary approaches to modelling marine microbial populations and functionality are feasible and practical in time-varying, space-resolving settings and provide a new tool for exploring evolutionary interactions on a range of timescales in the ocean.