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Abstract Background Preventing intimate partner violence or dating violence (DV) among adolescents is a public health priority due to its magnitude and damaging short and long-term consequences for adolescent and adult health. In our study protocol, we complement prior experiences in DV prevention by promoting protective factors (or assets) against gender violence such as communication skills, empathy and problem-solving capability through “Cinema Voice”, a participatory educational intervention based on adolescents’ strengths to tackle DV. Methods/design A longitudinal quasi-experimental educational intervention addressed to boys and girls ages 13–17 years, enrolled in secondary education schools in Alicante (Spain), Rome (Italy), Cardiff (UK), Iasi (Romania), Poznan (Poland) and Matosinhos (Portugal). Both process and results evaluations will be carried out with 100–120 intervention and 120–150 control group students per city at three time periods: before, after and 6 months after the implementation of the following interventions: 1) Training seminar with teachers to promote knowledge and skills on the core issues of intervention; 2) Workshops with intervention groups, where participants produce their own digital content presenting their perspective on DV; and 3) Short film exhibitions with participants, their families, authorities and other stakeholders with the objective of share the results and engage the community. Outcome measures are self-perceived social support, machismo, sexism, tolerance towards gender violence, social problem-solving and assertiveness as well as involvement in bullying/cyberbullying. Other socio-demographic, attitudes and violence-related co-variables were also included. Discussion This study may provide relevant information about the effectiveness of educational interventions that combine a positive youth development framework with educational awareness about the importance of achieving gender equality and preventing and combating gender violence. To our knowledge, this is the first study that involves six European countries in an educational intervention to promote violence protective assets among enrolled adolescents in secondary schools. This study may provide the needed tools to replicate the experience in other contexts and other countries. Trial registration Clinicaltrials.gov: NCT03411564. Unique Protocol ID: 776905. Date registered: 18-01-2018.

While triple-negative breast cancer (TNBC) is known to be heterogeneous at the genomic and transcriptomic levels, spatial information on tumor organization and cell composition is still lacking. Here, we investigate TNBC tumor architecture including its microenvironment using spatial transcriptomics on a series of 92 patients. We perform an in-depth characterization of tumor and stroma organization and composition using an integrative approach combining histomorphological and spatial transcriptomics. Furthermore, a detailed molecular characterization of tertiary lymphoid structures leads to identify a gene signature strongly associated to disease outcome and response to immunotherapy in several tumor types beyond TNBC. A stepwise clustering analysis identifies nine TNBC spatial archetypes, further validated in external datasets. Several spatial archetypes are associated with disease outcome and characterized by potentially actionable features. In this work, we provide a comprehensive insight into the complexity of TNBC ecosystem with potential clinical relevance, opening avenues for treatment tailoring including immunotherapy., Competing Interests: Competing interests: J.L., S.S., K.T., E.G.V. and N.B. are scientific advisors for 10xGenomics Inc. The remaining authors declare no competing interests., (© 2024. The Author(s).)

Importance: Evidence suggests that patients with human epidermal growth factor receptor 2-positive (ERBB2+ [formerly HER2+]) metastatic breast cancer (MBC) have different clinical characteristics and outcomes according to their hormone receptor (HR) status. The place of endocrine therapy (ET) for patients with HR+/ERBB2+ is still not clearly defined in this setting., Objective: To evaluate the association of HR status and first-line inclusion of ET with outcomes among patients with ERBB2+ MBC., Design, Setting, and Participants: This cohort study was an analysis of clinical data from the French clinical Epidemiological Strategy and Medical Economics (ESME) cohort, including patients with MBC who started treatment between 2008 and 2017. The last date of follow-up was June 18, 2020. Data were analyzed from May 2021 to May 2022., Exposures: Patients were treated with first-line ERBB2-targeted therapy and either chemotherapy (CT) with or without ET or ET alone. For the study of the association of maintenance ET with outcomes, we included patients treated with first-line ERBB2-targeted therapy with CT and with or without maintenance ET., Main Outcomes and Measures: Median overall survival (OS) and median first-line progression-free survival (PFS) were reported using the Kaplan-Meier method. Cox proportional hazards models and a propensity score were constructed to report and adjust for prognostic factors. Multivariable analysis included age at MBC, time to MBC, number of metastatic sites, type of metastases, and Eastern Cooperative Oncology Group performance status., Results: Among 4145 women with ERBB2+ MBC, 2696 patients had HR+ (median [IQR] age, 58.0 [47.0-67.0] years) and 1449 patients had HR- (56.0 [47.0-64.0] years) tumors. The median OS for patients with HR+ vs HR- tumors was 55.9 months (95% CI, 53.7-59.4 months) vs 42.0 months (95% CI, 38.8-45.2 months), confirmed in multivariable analysis (hazard ratio, 1.40; 95% CI, 1.26-1.56; P < .001). The median PFS for patients with HR+ vs HR- tumors was 12.2 months (95% CI, 11.5-12.9 months) vs 9.8 months (95% CI, 9.2-11.0 months; P = .01), and the HR was 1.15 (95% CI, 1.06-1.26; P < .001). In multivariable analysis, no significant difference was found in OS or PFS for 1520 patients treated with ERBB2-targeted therapy with CT and with or without ET vs 203 patients receiving ERBB2-targeted therapy with ET, regardless of type of ERBB2-targeted therapy (trastuzumab or trastuzumab with pertuzumab). This result was confirmed by matching patients using a propensity score. Using the time-dependent ET variable among patients with ERBB2-targeted therapy with CT, those with maintenance ET had significantly better PFS (hazard ratio, 0.70; 95% CI, 0.60-0.82; P < .001) and OS (hazard ratio, 0.47; 95% CI, 0.39-0.57; P < .001)., Conclusions and Relevance: These results suggest that ET-containing first-line regimens may be associated with benefits among a subgroup of patients with HR+/ERBB2+ MBC.

Background: As a result of progress in diagnosis and treatment, there is a growing prevalence of metastatic breast cancer (MBC) with isolated CNS metastases. This study describes the largest-to-date real-life cohort of this clinical setting and compares it to other clinical presentations., Methods: We retrospectively analysed the French Epidemiological Strategy and Medical Economics (ESME) MBC database including patients who initiated treatment for MBC between 2008 and 2016. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Descriptive statistics and multivariate Cox model were used., Results: Of 22,266 patients, 647 (2.9%) and 929 (4.2%) patients had isolated first-site CNS metastases or combined with extra-CNS metastases, with longer OS for the group with isolated CNS metastases (16.9 versus 13.9 months, adjusted HR = 1.69 (95% CI: 1.50-1.91), p  < 0.001). Among the 541 (2.4%) patients with isolated CNS metastases and no intrathecal therapy (excluding leptomeningeal metastases), HER2+ cases were preponderant over TN or HR+ /HER2- cases (41.6% versus 26.1% versus 28.5%, respectively, p  < 0.01). The treatment strategy consisted of a combination of local treatment and systemic therapy (49.2%), local treatment only (35.5%) or systemic therapy only (11.4%), or symptomatic therapy only (3.9%). Median PFS was 6.1 months (95% CI: 5.7-6.8). Median OS was 20.7 months (95% CI: 17.3-24.3), reaching 37.9 months (95% CI: 25.9-47.6) in the HR+ /HER2+ subgroup. Older age, TN subtype, MBC-free interval of 6-12 months, lower performance status, and WBRT were associated with poorer survival. Patients who received systemic therapy within 3 months from MBC diagnosis had longer OS (24.1 versus 16.1 months, p  = 0.031), but this was not significant on multivariate analysis [HR = 1.0 (95% CI: 0.7-1.3), p  = 0.806]., Conclusions: Patients with isolated CNS metastases at MBC diagnosis represent a distinct population for which the role of systemic therapy needs to be further investigated in prospective studies., Competing Interests: Conflict of interest statement: The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: JSF reports consulting fees from Novartis, Pfizer, AstraZeneca, Lilly, Roche, Biocad, Daiichi, Tesaro, GSK, Pierre Fabre. TB reports honoraria from Novartis, Roche, Pfizer, AstraZeneca and Seattle Genetics. The other authors report no conflicts of interest., (© The Author(s), 2022.)

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

Background: Neurologic complications as myelitis are very rare but extremely deleterious adverse effects of both immunotherapy and radiotherapy. Many recent studies have focused on the possible synergy of these two treatment modalities due to their potential to enhance each other's immunomodulatory actions, with promising results and a safe tolerance profile., Case Presentation: We report here the case of a 68-year-old man with metastatic non-small-cell lung cancer (NSCLC) who developed myelitis after T12-L2 vertebral radiotherapy, with motor deficit and sphincter dysfunction, while on treatment with pembrolizumab (an immune checkpoint inhibitor). The spinal abnormalities detected by magnetic resonance imaging (MRI), suggestive of myelitis, faithfully matched the area previously irradiated with 30 Gy in 10 fractions, six and a half months earlier. After immunotherapy discontinuation and steroid treatment, the patient rapidly and completely recovered. On progression, pembrolizumab was rechallenged and, after 8 cycles, the patient is on response and there are no signs of myelitis relapse., Conclusion: The confinement within the radiation field and the latency of appearance are suggestive of delayed radiation myelopathy. Nevertheless, the relatively low dose of radiation received and the full recovery after pembrolizumab discontinuation and steroid therapy plead for the contribution of both radiotherapy and immunotherapy in the causality of this complication, as an enhanced inflammatory reaction on a focal post-radiation chronic inflammatory state. In the three previously described cases of myelopathy occurring after radiotherapy and immunotherapy, a complete recovery had not been obtained and the immunotherapy was not rechallenged. The occurrence of a radiation recall phenomenon, in this case, can not be excluded, and radiation recall myelitis has already been described with chemotherapy and targeted therapy. Safe rechallenges with the incriminated drug, even immunotherapy, have been reported after radiation recall, but we describe it for the first time after myelitis.

Introduction : In hormone receptor-positive breast cancer, ESR1 mutations have emerged as a key mechanism of resistance to endocrine therapy. Areas covered : Here, we review currently available data on ESR1 mutations, regarding their functional impact, prevalence at different stages (and according to the material used: tissue-based analysis vs. liquid biopsy), prognostic impact and predictive value of resistance to aromatase inhibitors. Possible strategies to overcome this resistance by using selective estrogen receptor downregulators (such as fulvestrant) are also discussed. Expert opinion : ESR1 mutation detection will probably become a prognostic and predictive biomarker in the future, used in clinical practice for hormone-receptor breast cancer, especially in the metastatic setting. In the future, we should expect to assess ESR1 mutations, using liquid biopsy (by digital-PCR or next-generation sequencing), in the same way as other prognostic or predictive biomarkers, such as EGFR mutations in lung cancer, and possibly even have targeted-therapies against these mutations.