Cervical cancer is caused by persistent infection with high-risk human papillomaviruses (HR-HPV). Current screening programs rely on cytology and HR-HPV molecular detection. However, as most infections are transient, effective triage for HR-HPV positive women is crucial to identify those at high risk of progression to cancer. DNA methylation analysis, an epigenetic modification involved in HPV-induced oncogenesis, is emerging as a promising triage tool. This marker could stratify risk, thereby reducing invasive examinations (colposcopies) and unnecessary overtreatment (conizations), which may impact future pregnancies. Methylation tests, applicable to both cervical smears and self-collected vaginal samples, target viral genes (e.g., L1, L2) or host cell genes (e.g., FAM19A4, CADM1, MAL). While many markers show good performance, their optimal place in screening strategies and the choice of the most relevant test are still under investigation and require further comparative studies.

The evolution of serous high grade ovarian cancer management is characterized by a more regulated patients' journey on the one hand and the development of new therapeutic options on the other hand, the selection of which is guided by tumor molecular characteristics. Surgery remains the cornerstone of treatment. It can be performed only in authorized expert sites that can demonstrate sufficient experience from highly skilled surgical teams, and quality criteria including prehabilitation and rehabilitation programs. The diagnostic step is crucial; it comprises multiple biopsies that allow reliable pathological and molecular analyses, and a comprehensive surgical staging. Determination of BRCA1/2 mutation and homologous recombination deficiency statuses by validated methods guide maintenance therapy at advanced stages and referring to oncogenetic consultation if appropriate. For these advanced diseases, the two main questions for surgical strategy are the feasibility of complete resection (without residual disease, CC-0), assessed during surgical exploration of pelvis and abdomen, and the optimal timing of this surgery (upfront or after neoadjuvant chemotherapy). In recurrent diseases, surgery remains a main piece of treatment in case of late relapse and medical treatment depends on drugs used in the first line; in early platinum resistant relapse, a new therapeutic option is available with mirvétuximab soravtansine.

This article reviews a selection of recent developments in various fields of endocrinology. Advances in the diagnosis and management of endocrine disorders of general interest are highlighted, focusing on the following areas: a) new recommendations for the diagnosis and management of primary hyperaldosteronism; b) confirmation of the validity of therapeutic deescalation in low-risk differentiated thyroid cancer and c) the expansion of indications for genetic testing in multiple endocrine neoplasia syndromes.

Ewing sarcoma (ES) is an aggressive sarcoma with a peak incidence in adolescents and young adults. Current therapy involves multiagent chemotherapy and local therapy but despite intensification of treatment patients with metastases at diagnosis and recurrent disease have poor prognosis. Improved understanding of ES biology has identified novel targets with promising activity in ES patients. Tyrosine kinase inhibitors are currently being evaluated as combination and maintenance therapy. Other emerging therapies include those that target the EWSR1:FLI1 fusion oncoprotein, cell cycle, apoptotic and DNA-repair pathways. Immunotherapeutic approaches are also being investigated, particularly CAR-T and CAR-NK cell therapy. Close collaboration between clinicians and biologists has also highlighted the importance of biomarkers that are still being validated prospectively and might be incorporated into standard of care in the future.

Over the past 30 years, since the identification of the BRCA1 and BRCA2 genes, the panorama of breast cancer predisposition tests has continued to evolve: today, ultra-high-throughput sequencing enables the study of eight predisposition genes, and indications are constantly expanding, with the new entry point being the identification of BRCA1/2 alterations in tumors, 75% of which are of constitutional origin. While these tests can be used to provide appropriate preventive treatment in cases where risk factors have been identified, many challenges remain to be met: identification of new predisposition genes, or rather validation of candidate genes such as ATM, detection of new modes of inactivation of genes already included in the diagnosis (remote deletions, epigenetic modifications), classification of variants of unknown significance as pathogenic or benign, and identification and inclusion of modifying factors, whether genetic or not, in multifactorial risk models. Patients and their relatives have played, and continue to play, a major role in the development of oncogenetics. We owe them quality tests, information, support and protection.

Histopathological examination is a cornerstone in the diagnosis, prognostic stratification, and therapeutic planning of breast cancer. It combines morphological, immunophenotypic, and molecular data to guide clinical decision-making. This article provides a comprehensive overview of the main histological types, technical modalities, and conventional and emerging biomarkers in breast cancer pathology. Breast carcinomas are categorized into in situ (DCIS, LCIS) and invasive forms. The most frequent invasive types are invasive carcinoma of no special type (NST) and invasive lobular carcinoma (ILC). Rare histologic variants (e.g., mucinous, micropapillary, metaplastic) exhibit distinct biological and prognostic features. The diagnostic workflow includes standardized steps: sampling, formalin fixation, paraffin embedding, H&E staining, immunohistochemistry (ER, PR, HER2, Ki-67), and molecular testing when needed (FISH, PCR, NGS). Routine biomarkers help define surrogate molecular subtypes (luminal A/B, HER2-positive, triple-negative) and guide systemic therapies. The emergence of the HER2-low category exemplifies how biomarker refinement impacts clinical practice. Additional markers such as PIK3CA and ESR1 mutations, BRCA/HRD status, PD-L1 expression, and tumor-infiltrating lymphocytes (TILs), along with multigene signatures (e.g., Oncotype DX, MammaPrint), further individualize prognostic assessment and treatment selection. Innovative approaches such as liquid biopsy and next-generation sequencing (NGS) enable minimally invasive monitoring and personalized care, especially in advanced disease. Breast cancer pathology is thus a dynamic, integrative discipline central to precision oncology, driven by ongoing technological and molecular advances, and essential to multidisciplinary cancer care.

The rising incidence of cancer and the frequent resistance to treatments are driving the scientific community to explore new biological frontiers in search of concrete solutions for personalized patient care. These initiatives are made possible by the ongoing development of innovative technologies, which are shedding new light on our understanding of biological mechanisms. One such area is ribonucleic acid (RNA) chemical modifications-known as the epitranscriptome-which play a key role in all post-transcriptional stages of gene expression. An increasing number of studies are linking these modifications to tumor progression and treatment resistance. Functionally, epitranscriptomic modifications are orchestrated by a set of proteins known as "writers", "erasers" and "readers" which respectively add, remove, or read these chemical marks on RNA. The expression of these regulatory proteins is often dysregulated in cancer, thereby contributing to carcinogenesis. Clinically, these modifications are relevant across the entire patient care continuum, including diagnostic, prognostic, predictive, and therapeutic aspects. Many epitranscriptomic marks are associated with overall survival, tumor stage, the presence of metastases, or the detection of specific cancer types. They can enhance treatment efficacy or help anticipate resistance by modulating gene expression in target cells and revealing molecular signatures associated with therapeutic escape mechanisms. Moreover, inhibitors targeting epitranscriptomic regulatory proteins are currently under development and being evaluated in clinical trials, paving the way for novel therapeutic strategies in oncology.

This review aims to describe the role of poly-ADP-ribose polymerase inhibitors (PARPi) in the treatment of metastatic castration-resistant prostate cancer (mCRPC), an aggressive and lethal form of the disease. The introduction of PARPi has led to improved prognosis, particularly in patients with at least one somatic or germline mutation in DNA damage repair genes such as BRCA1 or BRCA2. Several recent studies have shown that PARPi, used alone or in combination with abiraterone or enzalutamide, improve progression-free survival and overall survival in patients with mCRPC. However, whether the three PARPi evaluated in phase 3 trials are therapeutically equivalent, and whether combination therapies should be recommended as first-line treatment for all mCRPC patients or reserved for those carrying mutations, particularly BRCA1/2, remain to be determined.

Granulosa cell tumors (GCTs) are rare ovarian neoplasms, accounting for 2-5% of all ovarian cancers. Two histological types have been described: juvenile (JGCT) and adult (AGCT), the latter accounting for around 95% of the GCTs. AGCTs are mostly diagnosed at an early stage and commonly have a good prognosis. However, GCTs tend to be associated with late recurrence in about a third of cases which are a major concern. These recurrences often require repeated surgical interventions. Systemic treatments, for their part, show limited effectiveness in this context, highlighting the need to identify new therapeutic targets. Thus, better biological characterization of these tumors would enable us to propose more targeted treatments. To achieve this, the molecular characteristics of GCTs have been explored. Most AGCTs harbor a mutation in the FOXL2 transcription factor sequence, therefore allowing to investigate therapeutic perspectives targeting its signalling, as well as setting the first steps towards immunotherapy in these tumors. Knowledge of JGCTs is more limited due to their rarity. However, molecular analysis revealed that ∼60% of the JGCTs bore a genetic mutation in the AKT1 oncogene. However, its clinical significance has still to be explored. For both GCTs subtypes, the CDK4/6-Rb1 axis is promising. Consequently, exploring the molecular features and their role in the biology of these tumors could open up new avenues for targeted and personalized therapies, thereby improving patient care.

Molecular biologists play an important role in therapeutic decisions in the context of Chronic Myelogenous Leukemia (CML). Before treatment, it is mandatory to identify the BCR::ABL1 fusion and any prognostic cytogenetic abnormalities that may be present. During treatment, regular assessment of measurable residual disease (MRD) is essential to objectively evaluate the optimal response and identify situations of resistance to treatment. Monitoring of MRD is also required when considering treatment discontinuations. In cases of resistance, identifying mutations that confer resistance to tyrosine kinase inhibitors is essential for adapting the treatment. The Group of Molecular Biologists of Hematologic Malignancies (GBMHM) and the France Intergroup of Chronic Myeloid Leukemia (Fi-LMC) convened a panel of experts to critically review methods used for molecular diagnostics and follow-up of patients with CML, define best practices applicable in this context and formulate recommendations.

Over the past decade, targeted therapies have significantly improved the prognosis of metastatic breast cancer. CDK4/6 and PARP inhibitors are now gaining traction in the adjuvant setting, and their potential use in the neoadjuvant context is also being explored. This review presents an analysis of the current scientific evidence and associated clinical perspectives. CDK4/6 inhibitors act on cell cycle dysregulation, commonly observed in hormone receptor-positive breast cancers. In the adjuvant setting, abemaciclib and ribociclib have shown improvements in progression-free survival (PFS) in the monarchE and NATALEE trials, respectively, leading to their approval by the European Medicines Agency. In the neoadjuvant context, although these agents have demonstrated a reduction in proliferation markers such as Ki67, their impact on clinical practice remains limited to date. PARP inhibitors are based on the concept of synthetic lethality, specifically targeting cancers with germline BRCA1 or BRCA2 mutations. In the adjuvant setting, the OlympiA trial demonstrated a significant improvement in both PFS and overall survival (OS). In the neoadjuvant setting, these agents have also shown effects on pathological markers, though the clinical relevance of these findings has yet to be clearly established. Overall, these results underscore the growing role of targeted therapies in the adjuvant management of breast cancer. The identification and validation of predictive biomarkers will be crucial in optimizing their use, both in adjuvant and neoadjuvant settings.

Diagnosis of central nervous system tumors is based on the histopathologic features and molecular alterations. For certain entities, this histomolecular diagnosis now includes DNA methylation profiles. Methylation profiles reflect the cell of origin and epigenetic modifications that occur during tumorigenesis and may help classify central nervous system tumors via artificial intelligence algorithms. This powerful approach to tumor classification has revolutionized the field of neuro-oncology, allowing more reliable diagnosis and prognostic assessment, particularly for pediatric neoplasms. The analysis of methylation profiles currently requires data to be shared with the developer of the AI algorithms. As DNA methylation profiling may be useful in a growing number of cancers, local alternatives, such as those based on the nanopore technology, need to be developed.

Antibodies-drugs conjugate (ADC) are revolutionizing breast cancer treatment thanks to their specific targeting and cytotoxic efficacy. Despite significant advances with agents such as trastuzumab emtansine, sacituzumab govitecan and trastuzumab deruxtecan, resistance mechanisms limit their efficacy. These include reduced or heterogeneous expression of the antigenic target on the surface of tumour cells (HER2, TROP2), mutations in genes encoding the targets of cytotoxic agents, increased efflux of these agents out of the cell, and alterations in intracellular trafficking. These resistances are associated with reduced efficacy of ADCs, underlining the need for new strategies, such as the development of next-generation ADCs by optimizing conjugation systems, for example. Therapeutic prospects also include the development of bispecific antibodies, the targeting of new proteins such as HER3, and the combination of ADCs with other treatments, notably immune checkpoint inhibitors or other ADCs. Despite these advances, challenges remain, notably in identifying biomarkers of response and defining the optimal therapeutic sequence to avoid cross-resistance. Ongoing research is aimed at refining the use of ADCs to maximize their efficacy and prolong the survival of breast cancer patients.

In France breast cancer is the most common cancer among women and the leading cause of cancer deaths. Identifying women with a "high" or "very high" breast cancer risk, according to the terminology of the Haute Autorité de santé 2014 guidelines, is essential to offer them special cares in term of screening and prevention. Women genetically predisposed have a very high risk of breast cancer. During the oncogenetic specialist consultation, familial and personal history of cancer is considered to evaluate the risk of hereditary Breast/Ovarian syndrome and thus the need of a genetic screening. In 2017 a list of 13 genes involved in hereditary ovarian or breast cancer has been established in France (Genetic and Cancer Group - Unicancer). Women carrying a BRCA1, BRCA2, PALB2, TP53, CDH1, PTEN mutation have a higher risk of breast cancer and are considered as "high risk". Therefore medical breast surveillance similar to carriers of BRCA1/BRCA2 mutation is recommended for these patients (INCa guidelines 2017). However a mutation in one of those genes is only identified in approximatively 10% of the screened families. The oncogenetic specialist's assessment distinguishes families in which women remain at a "high" risk of breast cancer (HAS 2014 for screening) from those where women have a "very high" risk (INCa guidelines 2017 for screening and prevention).

Breast cancer affects 5% of women of childbearing age, accounting for 30% of cancer cases in this population. These cancers are often more aggressive with a less favorable prognosis in younger women. Hormonal exposure plays a key role in the development of this cancer, although the specific impact of certain exposures, such as hormonal contraception or ovarian stimulation treatments, remains debated. Studies on the link between hormonal contraception and breast cancer risk present contradictory results. Some suggest a slight increase in risk, particularly after prolonged use, while others find no significant association. Regarding assisted reproductive technology, data show no increased risk of breast cancer after ovarian stimulation. For women with breast cancer, fertility preservation is possible before the implementation of gonadotoxic treatments without significantly impacting the risk of recurrence. Pregnancy after breast cancer, including hormone-dependent cancer, is not associated with a higher risk of recurrence. Lastly, women with BRCA mutations would face an increased risk of reduced ovarian reserve, but fertility preservation, as well as the use of contraception or hormone replacement therapy, can be considered in this high-risk population.

Breast cancer in adolescents and young adults (AYAs) is a rare event but requires a well-structured and tailored approach for this specific population. Oncogenetic and oncofertility consultations are essential at the time of breast cancer diagnosis in an AYA. Therapeutic management follows breast cancer guidelines, with particular attention to the risks of long-term side effects, potential constitutional genetic mutations, and specific considerations regarding hormone therapy. The number of adults who have survived cancer during childhood or adolescence/young adulthood increases each year. The morbidity associated with prior treatments and the risk of secondary cancers create needs for care and follow-up, which must be organized, anticipated, and adapted.

THE CONTRIBUTION OF HIGH-THROUGHPUT SEQUENCING IN MALIGNANT HEMATOLOGICAL DISORDERS. The development of cancers is largely attributed to somatic mutations in genes, imparting a selective advantage to cells, allowing for their progressive expansion. Thanks to the rise of high-throughput sequencing technologies, it is now possible to precisely characterize the genetic events that have contributed to tumorigenesis and extract clinically relevant information from them. After outlining the technical and bioinformatic steps required for these analyses, we present their primary consensus indications for positive diagnosis, prognostic evaluation, and/or therapeutic target discovery in malignant hematological disorders. The prospects that new sequencing techniques off er for diagnosis in the years to come are also presented.

NEUROFIBROMATOSIS TYPE 1: RECENT ADVANCES. Neurofibromatosis type 1 (NF1) has been the subject of extensive research over the past decade, conducted by both French and international research groups. This work has led to significant advancements in the diagnosis, screening, and management of individuals with NF1. Current and future projects offer hope for new therapies targeting neurofibromas, whether plexiform or cutaneous, and effective against their malignant transformation.

Past decade was marked by development of several new drug for HR+/HER2- metastatic breast cancer leading to several major question in terms of strategy. We propose here to review state of art in terms of targeted therapy for advanced luminal breast cancer and how treatment strategy will be more and more personalized in a near future.