Characterization of HER2-low breast cancer in young women with germline BRCA1/2 pathogenetic variants: Results of a large international retrospective cohort study

Background: Breast cancer (BC) in women aged ≤40 years carrying germline pathogenetic variants (PVs) in BRCA1/2 genes is infrequent but often associated with aggressive features. Human epidermal growth factor receptor 2 (HER2)-low-expressing BC has recently emerged as a novel therapeutic target but has not been characterized in this rare patient subset. Methods: Women aged ≤40 years with newly diagnosed early-stage HER2-negative BC (HER2-0 and HER2-low) and germline BRCA1/2 PVs from 78 health care centers worldwide were retrospectively included. Chi-square test and Student t-test were used to describe variable distribution between HER2-0 and HER2-low. Associations with HER2-low status were assessed with logistic regression. Kaplan–Meier method and Cox regression analysis were used to assess disease-free survival (DFS) and overall survival. Statistical significance was considered for p ≤.05. Results: Of 3547 included patients, 32.3% had HER2-low BC, representing 46.3% of hormone receptor–positive and 21.3% of triple-negative (TN) tumors. HER2-low vs. HER2-0 BC were more often of grade 1/2 (p <.001), hormone receptor–positive (p <.001), and node-positive (p =.003). BRCA2 PVs were more often associated with HER2-low than BRCA1 PVs (p <.001). HER2-low versus HER2-0 showed better DFS (hazard ratio [HR], 0.86; 95% CI, 0.76–0.97) in the overall population and more favorable DFS (HR, 0.78; 95% CI, 0.64–0.95) and overall survival (HR, 0.65; 95% CI, 0.46–0.93) in the TN subgroup. Luminal A–like tumors in HER2-low (p =.014) and TN and luminal A-like in HER2-0 (p =.019) showed the worst DFS. Conclusions: In young patients with HER2-negative BC and germline BRCA1/2 PVs, HER2-low disease was less frequent than expected and more frequently linked to BRCA2 PVs and associated with luminal-like disease. HER2-low status was associated with a modestly improved prognosis

Examen pelvien en gynécologie et obstétrique ::recommandations pour la pratique clinique

Objectif : Élaborer des recommandations pour l’examen clinique pelvien en gynécologie et obstétrique. Matériel et méthodes : Un groupe de travail multidisciplinaire de 45 experts a été constitué, comprenant des représentants d’associations de patients et d’usagers du système de santé. L’ensemble du processus de ces recommandations a été mené indépendamment de tout financement. Il a été conseillé aux auteurs de suivre les règles du système GRADE® (Grading of Recommendations Assessment, Development and Evaluation) pour évaluer la qualité des preuves. Les limites potentielles de faire des recommandations fortes en présence de preuves de faible qualité ont été soulignées. Le comité a étudié 40 questions dans 4 domaines pour les femmes symptomatiques ou asymptomatiques (urgence, consultation gynécologique, maladies gynécologiques, obstétrique et grossesse). Chaque question a été formulée dans un format PICO (Patients, Intervention, Comparaison, Résultat) et les éléments de preuve ont été détaillés. La revue de la littérature et les recommandations ont été réalisées selon la méthodologie GRADE®. Résultats : Le travail de synthèse des experts et l’application de la méthode GRADE ont abouti à 27 recommandations. Parmi les recommandations formalisées, 17 présentaient un accord fort, 7 un accord faible et 3 un accord professionnel. Treize questions ont donné lieu à une absence de recommandation en raison du manque de preuves (pas de réponse dans la littérature). Conclusions : Les 27 recommandations ont permis de préciser quand un examen clinique est requis pour différentes situations cliniques gynécologiques et obstétricales. Ces recommandations intéressent tout professionnel impliqué dans la santé des femmes. La nécessité de réaliser un examen clinique chez certaines patientes dans certaines situations a été fondée sur des preuves scientifiques. Des recherches supplémentaires sont nécessaires pour étudier les avantages dans d’autres situations.Objective : To provide guidelines for the pelvic clinical exam in gynecology and obstetrics. Material and methods : A multidisciplinary experts consensus committee of 45 experts was formed, including representatives of patients’ associations and users of the health system. The entire guidelines process was conducted independently of any funding. The authors were advised to follow the rules of the Grading of Recommendations Assessment, Development and Evaluation (GRADE®) system to guide assessment of quality of evidence. The potential drawbacks of making strong recommendations in the presence of low-quality evidence were emphasized. Methods : The committee studied 40 questions within 4 fields for symptomatic or asymptomatic women (emergency conditions, gynecological consultation, gynecological diseases, obstetrics, and pregnancy). Each question was formulated in a PICO (Patients, Intervention, Comparison, Outcome) format and the evidence profiles were produced. The literature review and recommendations were made according to the GRADE® methodology. Results : The experts’ synthesis work and the application of the GRADE method resulted in 27 recommendations. Among the formalized recommendations, 17 present a strong agreement, 7 a weak agreement and 3 an expert consensus agreement. Thirteen questions resulted in an absence of recommendation due to lack of evidence in the literature. Conclusions : The need to perform clinical examination in gynecological and obstetrics patients was specified in 27 pre-defined situations based on scientific evidence. More research is required to investigate the benefit in other cases

Do women with suspected endometriosis benefit from pelvic examination to improve diagnostic and management strategy?

International audienceObjective: To analyze the literature and expose best evidence available regarding the benefit of pelvic exami-nation for women with suspected endometriosis Methods: the AGREE II and GRADE systems for grading scientific evidence. Results: Endometriosis is characterized by the heterogeneity in its clinical presentation with many different symptoms reported by patients. In the literature, questioning for each symptom has a high sensitivity, reaching 76–98 %, but lacks specificity (20 – 58 %). The symptom-based approach is limited by its low specificity, the absence of external validation for most of the models developed and the inability to characterize the extent of the disease, which could have major implications in the decision – making process. The latest systematic review and meta-analysis included a total of 30 studies with 4,565 participants, compared the diagnostic performance of several modalities for endometriosis. Physical examination had a pooled sensitivity of 71 % and a specificity of 69 %, with an average diagnostic accuracy of 0.76. Overall, the value of pelvic examination is conferred by its high positive likehood ratio and specificity. Besides its diagnostic value, pelvic examination improves patients’ management by allowing the identification of a possible myofascial syndrome as a differential diagnosis. It also increases the quality of the preoperative workup and influences the quality of surgical excision and decreases the time to diagnosis. Conclusion: Despite the lack of studies in the primary care context, pelvic examination (vaginal speculum and digital vaginal examination) increases the diagnostic value for suspected endometriosis in association with questioning for symptoms

Human Papilloma Virus Vaccination Among Female Patients Attending French Pediatric Cystic Fibrosis Centers

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Fertility Assessment after Ovarian Transposition in Children and Young Women Treated for a Malignant Tumor

Ovarian transposition (OT) has been proposed as a protective measure against radiation-induced damage to ovarian function and fertility. Despite its historical use, limited research has focused on evaluating endocrine and exocrine ovarian function after OT performed in adolescents and young adults (AYAs) before or during puberty. The purpose of our study was to investigate the fertility, pubertal development, and ovarian function of women with a previous history of OT during childhood, adolescence or young adulthood. In an observational bicentric retrospective study, we included 32 young female cancer patients who underwent OT before the age of 26 between 1990 and 2015 at Lyon Léon Bérard Cancer Center or Nancy University Hospital. The mean age at the time of OT was 15.6 years with a cancer diagnosis at 15 ± 4.8 years. Among the 10 women attempting pregnancy post-treatment, 60% achieved successful pregnancies. After a mean follow-up of 9.6 ± 7 years, 74% (17 out of 23) of women recovered spontaneous menstrual cycles (seven out of eight evaluable women with OT before or during puberty). Notably, 35% of women who did not attempt pregnancy demonstrated adequate ovarian reserve. Ovarian reserve and function recovery were influenced by the specific chemotherapy received. Importantly, our findings suggest that OT’s effectiveness on ovarian activity resumption does not significantly differ when performed before or during puberty compared to pubertal stages. This study contributes valuable insights into the long-term reproductive outcomes of young women undergoing OT, emphasizing its potential efficacy in preserving ovarian function and fertility across different developmental stages

Human Papilloma Virus Vaccination in Patients with Rheumatic Diseases in France: A Study of Vaccination Coverage and Drivers of Vaccination

International audienceObjectives: To describe human papillomavirus (HPV) vaccination practices in adolescent girls with systemic lupus erythematosus (SLE) and juvenile idiopathic arthritis (JIA) and to identify barriers to and motivators for vaccination. Methods: Cross-sectional, multicenter study on girls aged 9 to 19 years and their accompanying adults. The measurement criteria were the proportion of girls who were vaccinated against HPV, compliance with the vaccination schedule, factors associated with vaccination, and reasons for vaccination and non-vaccination through a self-administered questionnaire. Results: Seventy-one patients (16 with SLE and 55 with JIA) were included with a mean age of 13 years old (rank 11–18). According to parental questioning, 39% of patients were vaccinated against HPV or in progress (44% and 38% of SLE and JIA, respectively). This rate was 82% for the 22 patients ≥ 15 years of age. The vaccine was administered as often by a general practitioner (39%) as by a hospital pediatrician (also 39%). Two factors were significantly associated with vaccination: Older age (OR 53.68, 95% CI 5.85–429.29, p < 0.001) and previous hepatitis B vaccination (OR 4.97, 95% CI 1.03–24.01, p = 0.040). Recommendation of the vaccine by a health professional and fear of HPV-related diseases were the main facilitators. Lack of knowledge about the vaccine, lack of recommendation by a health professional, and fear of vaccine side effects were the main barriers. Conclusions: HPV vaccination coverage remains insufficient among patients with autoimmune disease. Education and awareness of health professionals about HPV infections are crucial elements in vaccine acceptance