This narrative review aims to clarify the role of tertiary lymphoid structures in breast cancer. We examine their development, composition, and prognostic value, and current ways of recognizing them. A comprehensive literature review was performed using the PubMed/Medline, Scopus, and EMBASE databases. A significant area of interest in breast cancer research involves targeting immune checkpoint molecules, particularly in the triple-negative subtype, where treatment options remain limited. However, existing biomarkers have limitations in accurately predicting treatment response. In this context, tertiary lymphoid structures (TLSs) emerge as a prognostic biomarker and also as a promising predictive marker for response. TLSs are ectopic lymphoid formations or neo-organogenesis that can develop after prolonged exposure to inflammatory signals mediated by chemokines and cytokines. Their presence is inversely correlated with estrogen receptor (ER) and/or progesterone receptor (PR) expression, but positively associated with a higher pathologic complete response rate and improved overall survival. In certain scenarios, TLS-positive tumors were associated with improved outcomes regardless of the presence of PDL-1 (programmed cell death ligand 1) expression or TILs (tumor-infiltrating lymphocytes).

Breast cancer remains a major global health challenge. In 2022, there were an estimated 2.3 million new cases and 670,000 deaths among women worldwide. Hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) breast cancer accounts for approximately 70% of breast cancer diagnoses. The treatment landscape for advanced HR+)/HER2− breast cancer has been transformed by the introduction of CDK4/6 inhibitors in the first-line setting. However, therapeutic strategies following progression on CDK4/6 inhibitors remain heterogeneous and uncertainty exists in their optimal integration in clinical practice. This review aims to systematically examine available second-line and subsequent treatment options for HR+/HER2− metastatic breast cancer after progression on CDK4/6 inhibitors, with a focus on biomarker-driven strategies and emerging therapies. The therapeutic landscape beyond CDK4/6 inhibitors includes targeted agents guided by actionable biomarkers as well as novel selective estrogen receptor degraders (SERDs). In biomarker-unselected populations, options include CDK4/6 continuation strategies, endocrine monotherapy in selected cases, and cytotoxic therapy. The integration of molecular testing via next-generation sequencing has become standard of care in guiding these decisions. However, overlapping molecular alterations and a lack of consensus on treatment sequencing pose significant challenges. Prognostic factors such as circulating tumor DNA dynamics may further refine treatment personalization. Post-CDK4/6 therapy in HR+/HER2− metastatic breast cancer is an evolving and increasingly complex area of practice. Optimal treatment selection should be tailored to both tumor biology and patient-specific factors, supported by molecular testing and high-quality evidence.

The role of modern parameters and their relationship with recurrence risk as assessed by Oncotype DX: real-world evidence Dana Narvaez, Jorge Nadal, Adrian

Background: The management of hormone receptor-positive (HR+), HER2-negative early breast cancer in young women presents unique challenges due to the absence of standardized guidelines and variability in clinical decision-making. In Latin America, these challenges are compounded by disparities in healthcare systems and limited access to genomic testing and supportive services. Objectives: To evaluate current attitudes, diagnostic strategies, and treatment practices among Latin American oncologists regarding the care of young women with HR+ early breast cancer. Design: A cross-sectional survey study targeting practicing oncologists across Latin America. Methods: A 30-item online questionnaire was distributed to 329 oncologists from 17 Latin American countries. The survey explored physician demographics, access to diagnostic tools, treatment preferences, and availability of support services, including genetic counseling and fertility preservation. Results: The findings revealed significant heterogeneity in clinical practices. Among patients with a Recurrence Score (RS) of 20–25, 53.8% of oncologists recommended adjuvant chemotherapy, while 23.4% considered additional clinicopathologic features. Fertility preservation counseling was inconsistently offered: 29.5% provided it routinely, whereas 12.5% never did. Ovarian function suppression (OFS) was universally recommended by 46.2% of respondents, with breast cancer specialists showing more nuanced use than non-specialists ( p = 0.019). Access to genetic counseling was limited, with 12.5% reporting no access. Temporary interruption of endocrine therapy to pursue pregnancy was supported by 41.0% of respondents, though approaches varied. Female oncologists were more likely to recommend extended endocrine therapy (73.2% vs 60.8%, p = 0.019) and to refer patients for sexual health support (19.3% vs 8.7%, p = 0.05). Conclusion: This study highlights considerable variability in the management of young women with HR+ early breast cancer across Latin America. Physician gender, specialty, and resource availability significantly influence treatment decisions. These findings underscore the urgent need for regionally tailored clinical guidelines and improved access to diagnostic and supportive care resources to ensure equitable and evidence-based care.

La inteligencia artificial (IA) está transformando aceleradamente el diseño y la ejecución de ensayos clínicos, al ofrecer herramientas para el análisis de grandes volúmenes de datos clínicos, genómicos e imagenológicos. Esta mini revisión analiza el estado del arte sobre el uso de IA en investigación clínica en oncología y discute los principales marcos regulatorios internacionales (OMS, EMA, FDA) y regionales, junto con los desafíos específicos en América Latina y en Argentina. Se identificaron tanto los beneficios potenciales como los riesgos asociados a la IA, entre ellos los sesgos algorítmicos y las limitaciones en la representatividad de los datos utilizados. Se revisaron también los esfuerzos regulatorios emergentes, como la Ley de Inteligencia Artificial de la Unión Europea y los principios éticos propuestos por la OMS y la OPS. En el plano nacional, Argentina presenta fortalezas en infraestructura sanitaria, red de centros de investigación, y participación de CROs internacionales, además de una creciente inversión en Innovacion y desarrollo. Esta revisión propone estrategias para acelerar una adopción ética, robusta y eficiente de la IA en ensayos clínicos, destacando la necesidad de marcos regulatorios actualizados, multidisciplinariedad y cooperación internacional.

Background: Next-generation sequencing (NGS) has proven to be a key implementation to understanding biological pathways involved in cancer. In daily practice, the identi-fication of somatic and germline mutations has allowed physicians to gather relevant information to make therapeutic decisions and benefit patients. Importantly, somatic mutations provide targeted opportunities for treatment and reveal resistance mecha-nisms to understand patients' tumour evolution. Scanty data in clinical trials and in a real-world setting is available regarding the utility of poly(ADP-ribose) polymerase inhibi-tors in pathogenic or likely-pathogenic somatic breast cancer gene 1/2 (BRCA1/2) muta-tions and/or germline or somatic Homologous Recombination-Related Gene mutations in advanced breast cancer (ABC).Case report: Here we report a real-life case of a 47-year-old postmenopausal woman with hormone receptor-positive (HR-positive) Epidermal growth factor receptor 2 (HER2)-negative metastatic BC that had poor response to classic therapeutic strategies for HR+/HER2- ABC. At this point, the possibility of using NGS to guide the treatment was decided in a Molecular Tumour Board (MTB), and the patient had a major response to talazoparib targeting a non-germline BRCA2 mutation.Conclusion: Undoubtedly, more information regarding the cost effectiveness of NGS is needed to develop adequate reimbursement policies for this technology. It should be highlighted that the generalisation of MTBs and the implementation of molecular screen-ing programmes are greatly needed in our region to gain more knowledge of somatic mutations implicated in the Hispanic and Latin-American population with BC diagnosis. Recently presented results of randomised studies may support the evaluation of somatic mutations with NGS to find targeted therapies for ABC patients.