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Over the last decade, various entrepreneurial school practices have proliferated, including the creation of mini-companies. In the Spanish context, the Empresa Joven Europea (EJE) program has been the most widely employed educative program in this respect. Empresa Joven Europea is an educational program that proposes that secondary education students create and manage their own mini-businesses, thereby taking the legal form of a cooperative society and facilitating the acquisition of all basic educational skills through the cultivation of entrepreneurship. Nevertheless, there is still a gap between the theory and the practice of entrepreneurship education which, together with the conceptual expansion experienced in recent years, increases the need to assess the effectiveness of this type of programs. By means of an explanatory and cross-sectional study, we evaluated the impact of the program on the configuration of the entrepreneurial potential of the participating adolescents ( N = 270). The analysis has been carried out utilizing PLS-SEM with SmartPLS software version 3.3.9 and SPSS version 25. None of the six hypotheses formulated have been confirmed, which means that the desired effects have not been achieved in any of the three variables under study: attitudes, knowledge, and entrepreneurial skills. Such results may be related to aspects of curricular organization, the type of experiences based on cooperatives, a certain structural and conceptual lack of definition of the pedagogical methodology used, and the development of skills linked to identity. Moreover, it is possible that, although it is not evident in the competencies acquired, the program has influenced the apperception of what it means to be an entrepreneur and of the creation of critical awareness, which is associated with entrepreneurial potential. Our study, in addition to opening suggestions for further research along the same lines, presents several implications related to administrative and organizational aspects, to the design of the different pedagogical elements of the programs and to the evaluative criterion adopted.

Background The co-occurrence of chronic diseases and acute infectious events exacerbates disability and diminishes quality of life, yet research in Low- and Middle-Income countries is scarce. We aimed to investigate the relationship between infectious events and multimorbidity in resource-constrained settings. Methods We conducted a sequential mixed-method study in Lima and Tumbes, Peru, with participants having multimorbidity from the CRONICAS Cohort Study. They completed a questionnaire on the occurrence, treatment, and health-seeking behaviour related to acute infectious events. Qualitative interviews explored the perceptions and links between multimorbidity and acute infectious events for a subgroup of participants. Findings Among individuals with multimorbidity, low awareness of chronic conditions and poor medication adherence. The cumulative incidence for respiratory and gastrointestinal infections, the most reported acute conditions, was 2.0 [95%CI: 1.8–2.2] and 1.6 [1.2–1.9] events per person per year, respectively. Individuals with cancer (6.4 [1.6–11.2] events per person per year) or gastrointestinal reflux (7.2 [4.4–10.1] events per person per year) reported higher cumulative incidence of infectious events than others, such as those with cardiovascular and metabolic conditions (5.2 [4.6–5.8] events per person per year). Those with three or more chronic conditions had a slightly higher cumulative incidence compared with individuals with two conditions (5.7 [4.4–7.0] vs 5.0 [4.4–5.6] events per person per year). Around 40% of individuals with multimorbidity sought healthcare assistance, while others chose drugstores or didn't seek help. Our qualitative analysis showed diverse perceptions among participants regarding the connections between chronic and acute conditions. Those who recognized a connection emphasized the challenges in managing these interactions. Interpretation Our study advances understanding of multimorbidity challenges in resource-limited settings, highlighting the impact of acute infections on patients' existing multimorbidity burden.

Neoadjuvant chemotherapy was originally designed to convert inoperable cancer. Nowadays, this concept has expanded since it can also offer the possibility to evaluate markers of response such as pathological complete response (pCR) with possible implications in long-term prognostic outcomes. A substantial body of literature tried to evaluate the ability of pCR to fulfill the conditions required to establish a preliminary endpoint, such as pCR, as a surrogate for the final endpoint, the overall survival (OS) but no systematic reviews have been performed yet. In this review we systematically analyzed the prognostic role of pCR in various cancers (breast, gastro-oesophageal, rectal, ovarian, bladder, lung) in which neoadjuvant treatment is a standard of care, evaluating articles published in the English language of phase III or phase II randomized controlled trials and meta-analyses. Since the continue development of immunotherapy in earlier stage, it has also been considered the impact of tumor-infiltrating lymphocyte on pCR.

Background: The CDK4/6 inhibitor palbociclib combined with endocrine therapy (ET) has proven to prolong progression-free survival (PFS) in women with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) metastatic breast cancer (MBC). Few data are available regarding the efficacy of such a regimen outside the clinical trials. Patients and methods: This is a multicentre prospective real-world experience aimed at verifying the outcome of palbociclib plus ET in an unselected population of MBC patients. The primary aim was the clinical benefit rate (CBR); secondary aims were the median PFS, overall survival (OS) and safety. Patients received palbociclib plus letrozole 2.5 mg (cohort A) or fulvestrant 500 mg (cohort B). Results: In total, 191 patients (92 in cohort A, 99 in cohort B) were enrolled and treated, and 182 were evaluable for the analysis. Median age was 62 years (range 47–79); 54% had visceral involvement; 28% of patients had previously performed one treatment line (including chemotherapy and ET), 22.6% two lines and 15.9% three. An overall response rate of 34.6% was observed with 11 (6.0%) complete responses and 52 (28.6%) partial responses. Stable disease was achieved by 78 patients (42.9%) with an overall CBR of 59.8%. At a median follow-up of 24 months (range 6–32), median PFS was 13 months without significant differences between the cohorts. When analysed according to treatment line, PFS values were significantly prolonged when palbociclib-based therapy was administered as first-line treatment (14.0 months), to decrease progressively in second and subsequent lines (11.7 and 6.7 months, respectively). Median OS was 25 months, ranging from 28.0 months in 1st line to 18.0 and 13.0 months in 2nd and subsequent lines, respectively. Conclusions: Our data indicate that palbociclib plus ET is active and safe in HR+/HER2− MBC, also suggesting a better performance of the combinations in earlier treatment lines.

Background: Progesterone receptor (PgR) negative breast cancer (BC) is an aggressive subtype with poor prognosis and reduced response to endocrine treatments. Several studies have suggested that androgen receptor (AR) expression is associated with a favorable tumor biology, longer recurrence free survival (RFS), and overall survival. In the literature no data exist regarding the role of AR expression in early stage estrogen receptor (ER)+/PgR– BCs. The aim of this study was to evaluate the prognostic role of AR expression in this setting. Patients and methods: This is a monocentric retrospective study in which 208 patients who underwent surgical intervention for ER+/PgR−/Human Epidermal growth factor Receptor 2 (HER2)– BC were included. The primary objective was to analyze the relationship between AR expression and RFS. Results: At a median follow-up of 77 months, 75 patients (36%) had a disease relapse (all sites included). AR expression was significantly higher in patients who did not relapse compared with those who relapsed with an impact on RFS (hazard ratio [HR] = 0.99, p = 0.025). Patients with AR expression ⩾80% had a lower risk of relapse compared with those with AR

Objective: To characterize the prevalence and clustering of multimorbidity in four diverse geographical settings in Peru. Methods: Multimorbidity, defined as having ≥2 chronic conditions, was studied in adults aged ≥35 years in four diverse settings in Peru: Lima, Tumbes, and urban and rural Puno. Six of these conditions (alcohol disorder, asthma, chronic obstructive pulmonary disease, depression, diabetes, and hypertension) were cataloged as objectively ascertained chronic conditions and paired in dyads to explore clusters of multimorbidity. Results: We analyzed data from 2890 adults, mean age 55.2 years, 49% males. Overall, 19.1% of participants had multimorbidity, ranging from 14.7% in semi-urban Tumbes to 22.8% in Lima. The dyads with the highest coexistence (approximately 20%) were observed in hypertension and diabetes in Tumbes, whereas the dyads with lowest coexistence (approximately 1%) were those involving asthma in all study sites. In terms of clusters, Tumbes showed a predominance of hypertension and diabetes, urban and rural Puno a predominance of depression and alcohol disorders, and Lima a higher degree of coexistence of all of the six conditions than in the other clusters. Conclusion: Multimorbidity is common and the pattern of clusters is highly heterogeneous. The conditions to prioritize will vary in each setting.

Background: Fulvestrant 500 mg (F500) is the most active endocrine single agent in hormone receptor-positive (HR+)/HER2-negative metastatic breast cancer (MBC). Few data are available regarding the effectiveness of the drug in a real-world setting. Patients and methods: This prospective, multicenter cohort study aimed to describe the patterns of treatment and performance of F500 in a large population of unselected women with MBC, focusing on potential prognostic or predictive factors for disease outcome and response. The primary endpoints were progression-free survival (PFS) and clinical benefit rate. Results: From January 2011 to December 2015, 490 consecutive patients treated with F500 were enrolled. Overall, three different cohorts were identified and analyzed: the first received F500 after progression from previous chemotherapy (CT) or endocrine therapy; the second received the drug for de novo metastatic disease; and the third was treated as maintenance following disease stabilization or a response from a previous CT line. Median overall survival (OS) in the whole population was 26.8 months, ranging from 32.4 in first line to 22.0 and 13.7 months in second line and subsequent lines, respectively. Both the presence of liver metastasis and the treatment line were significantly associated with a worse PFS, while only the presence of liver metastasis maintained its predictive role for OS in multivariate analysis. Conclusions: The effectiveness of F500 was detected in patients treated both upon disease progression and as maintenance. The relevant endocrine sensitivity of 80% of patients included in the study could probably explain the good results observed in terms of outcome.

The therapeutic goals in metastatic breast cancer (MBC) remain palliative in nature, aimed at controlling symptoms, improving or maintaining quality of life and prolonging survival. The advent of new drugs and new formulations of standard agents has led to better outcomes in patients with advanced or metastatic disease. These developments have also allowed a tailored therapeutic approach, in which the molecular biology of the tumour, the treatment history, and patient attitudes are taken into account in the decision-making process. Targeting drug delivery to the tumour is a promising mean of increasing the therapeutic index of highly active agents such as the taxanes, and nanoparticle albumin-bound paclitaxel ( nab -paclitaxel), the first nanotechnology-based drug developed in cancer treatment, is one such advance. Data from randomized trials support the efficacy of single-agent nab -paclitaxel as first-line and further treatment lines in MBC at the registered 3-weekly schedule of 260 mg/m 2 , but emerging evidence suggests its activity as a weekly regimen or combined with other agents in various clinical scenarios. Thus, nab -paclitaxel seems to offer flexibility in terms of dosing schedules, allowing physicians to tailor the dose according to different clinical situations. This paper reviews the clinical trial background for nab -paclitaxel in MBC, focusing on specific ‘difficult-to-treat’ patient populations, such as taxane-pretreated or elderly women, as well as those with triple-negative, HER2-positive and poor-prognostic-factors disease. Moving beyond evidence-based information, ‘real life’ available experiences are also discussed with the aim of providing an update for daily clinical practice.

The outcome of patients with metastatic breast cancer (MBC) has clearly improved over the past decades and the proportion of women living with their disease for several years is increasing. However, the usefulness of multiple lines of treatment is still debated and under evaluation. The available data from both randomized trials and large retrospective series are reviewed and discussed in order to analyze management practices, with emphasis on potential prognostic and predictive factors for clinical outcome. At present, evidence-based medicine provides some support for the use of second-line and to a lesser degree and in selected cases, third-line chemotherapy in human epidermal growth factor receptor 2 (HER2) negative MBC. Beyond third-line treatment, messages from recently reported retrospective studies also suggest a clear potential gain for women receiving further therapies after disease progression, since each line can contribute to a longer survival. In HER2-positive disease, the data from observational and retrospective studies support a clinical benefit from the use of trastuzumab beyond disease progression and emerging evidences from randomized controlled trials are leading to the introduction of newer HER2-targeted therapies in multiple lines. The question ‘How many lines of treatment should we give patients?’ clearly needs further research through prospective, high-quality clinical trials, aiming for a better definition of factors with prognostic and predictive role. In the meantime, the ‘optimal’ treatment strategy should probably be to use as many therapeutic options as possible, either in sequence or combination, to keep the best efficacy/toxicity balance, considering MBC as a chronic disease.