Inflammatory breast cancer: Epidemiologic data and therapeutic results.

Since the early description more than a century ago, inflammatory breast cancer (IBC) remains an aggressive disease, with a different geographic repartition, with the highest ones incidence reported in the North of Africa (Tunisia, Algeria, Morocco, and Egypt), and the lowest incidence in Western countries (USA, Europe…). In this study, we reviewed the literature using the Surveillance, Epidemiology, and End Results (SEER) database compared to other published series. We observed that in the high incidence areas (North of Africa) when compared to "classical" breast cancer, IBC was associated to younger age (less than 50 years) with rapid evolution of signs and symptoms (in less than 3 up to 6 months), and more aggressive clinical and histopathological-molecular parameters, due to the predominance of triple-negative and HER2+ subtypes in around 60% of cases. An epidemiologic trend was observed in both high and low incidence areas since the eighties are towards reduction of IBC prevalence. Concerning Tunisia, in comparison with the historical series of the 1980s, the incidence decreased in part by applying more stringent diagnostic criteria but also probably due to a slight improvement of the socio-economic level (SEL). This trend was also observed in the US, due to the efforts of collaborative IBC groups from MD Anderson Cancer Center (MDACC), Duke and IBC patient advocacy groups. Therapeutic results are slightly better due to the standardization of a multidisciplinary approach and the use of combined primary chemotherapy and/or targeted therapies (especially in HER2 positive patients), followed by mastectomy plus radiotherapy. The 5-year overall and disease-free survival is at more than 60%, related to an IBC mortality decrease observed in the cohorts of patients treated in the last decade.

Navigating the Cancer Journey: Experiences and Perspectives of Young Adult Patients in Tunisia.

Purpose: This study aimed to explore the experiences of young adult cancer patients within the Tunisian context. Methods: A total of 104 patients between the ages of 20 and 40, undergoing treatment for various types and stages of cancer, participated in a questionnaire-based survey. The survey encompassed topics related to the socioeconomic and psychological impacts of cancer, coping mechanisms, relationships, sexuality, and future aspirations. Results: Of the participants, 78 were women (75%) and 26 were men (25%), with an average age of 33 years. Financial difficulties were reported by 60 patients (57.7%). The most common emotional responses to the diagnosis were sadness (54.8%), followed by denial (18.3%) and anger (5.8%). Thirteen patients (12.5%) choose not to receive information about the stage of their disease. In addition, 42 patients (40.4%) experienced a decrease in perceived physical attractiveness, while negative effects on sexuality were observed in 44.2% of cases. The primary concerns reported by patients were the fear of recurrence or progression (48%) and infertility (48%). Furthermore, 43 patients (41.3%) expressed a decrease in self-confidence, notably influenced by financial difficulties (OR: 2.77 [95% CI: 1.12-6.87]), physical alterations (OR: 0.18 [95% CI: 0.07-0.45]), and sexual issues (OR: 0.17 [95% CI: 0.06-0.48]). Notably, 78 patients (75%) continued to make future plans, particularly those under 30 years of age (OR: 0.2 [95% CI: 0.04-0.96]). Moreover, 47.1% of patients expressed an inclination toward immigration to developed countries, primarily due to perceived superior health care systems (61.5%). Conclusions: Young cancer patients face a range of social and psychological challenges, suggesting the necessity for a specialized care approach.

Uncovering the clinical relevance of unclassified variants in DNA repair genes: a focus on BRCA negative Tunisian cancer families.

Introduction: Recent advances in sequencing technologies have significantly increased our capability to acquire large amounts of genetic data. However, the clinical relevance of the generated data continues to be challenging particularly with the identification of Variants of Uncertain Significance (VUSs) whose pathogenicity remains unclear. In the current report, we aim to evaluate the clinical relevance and the pathogenicity of VUSs in DNA repair genes among Tunisian breast cancer families. Methods: A total of 67 unsolved breast cancer cases have been investigated. The pathogenicity of VUSs identified within 26 DNA repair genes was assessed using different in silico prediction tools including SIFT, PolyPhen2, Align-GVGD and VarSEAK. Effects on the 3D structure were evaluated using the stability predictor DynaMut and molecular dynamics simulation with NAMD. Family segregation analysis was also performed. Results: Among a total of 37 VUSs identified, 11 variants are likely deleterious affecting ATM, BLM, CHEK2, ERCC3, FANCC, FANCG, MSH2, PMS2 and RAD50 genes. The BLM variant, c.3254dupT, is novel and seems to be associated with increased risk of breast, endometrial and colon cancer. Moreover, c.6115G>A in ATM and c.592+3A>T in CHEK2 were of keen interest identified in families with multiple breast cancer cases and their familial cosegregation with disease has been also confirmed. In addition, functional in silico analyses revealed that the ATM variant may lead to protein immobilization and rigidification thus decreasing its activity. We have also shown that FANCC and FANCG variants may lead to protein destabilization and alteration of the structure compactness which may affect FANCC and FANCG protein activity. Conclusion: Our findings revealed that VUSs in DNA repair genes might be associated with increased cancer risk and highlight the need for variant reclassification for better disease management. This will help to improve the genetic diagnosis and therapeutic strategies of cancer patients not only in Tunisia but also in neighboring countries.

Genetic testing for hereditary cancer syndromes in Tunisian patients: Impact on health system.

INTRODUCTION: Cancer management in Africa faces diverse challenges due to limited resources, health system challenges, and other matters. Identifying hereditary cancer syndromic cases is crucial to improve clinical management and preventive care in these settings. This study aims to explore the clinicopathological features and genetic factors associated with hereditary cancer in Tunisia, a North African country with a rising cancer burden MATERIALS AND METHODS: Clinicopathological features and personal/family history of cancer were explored in 521 patients. Genetic analysis using Sanger and next-generation sequencing was performed for a set of patients RESULTS: Hereditary breast and ovarian cancer syndrome was the most frequent cluster in which 36 BRCA mutations were identified. We described a subgroup of patients with likely ''breast cancer-only syndrome'' among this cluster. Two cases of Li-Fraumeni syndrome with distinct TP53 mutations namely c.638G>A and c.733G>A have been identified. Genetic investigation also allowed the identification of a new BLM homozygous mutation (c.3254dupT) in one patient with multiple primary cancers. Phenotype-genotype correlation suggests the diagnosis of Bloom syndrome. A recurrent MUTYH mutation (c.1143_1144dup) was identified in three patients with different phenotypes CONCLUSION: Our study calls for comprehensive genetic education and the implementation of genetic screening in Tunisia and other African countries health systems, to reduce the burden of hereditary diseases and improve cancer outcomes in resource-stratified settings.

A regionally based precision medicine implementation initiative in North Africa:The PerMediNA consortium.

Precision Medicine is being increasingly used in the developed world to improve health care. While several Precision Medicine (PM) initiatives have been launched worldwide, their implementations have proven to be more challenging particularly in low- and middle-income countries. To address this issue, the "Personalized Medicine in North Africa" initiative (PerMediNA) was launched in three North African countries namely Tunisia, Algeria and Morocco. PerMediNA is coordinated by Institut Pasteur de Tunis together with the French Ministry for Europe and Foreign Affairs, with the support of Institut Pasteur in France. The project is carried out along with Institut Pasteur d'Algérie and Institut Pasteur du Maroc in collaboration with national and international leading institutions in the field of PM including Institut Gustave Roussy in Paris. PerMediNA aims to assess the readiness level of PM implementation in North Africa, to strengthen PM infrastructure, to provide workforce training, to generate genomic data on North African populations, to implement cost effective, affordable and sustainable genetic testing for cancer patients and to inform policy makers on how to translate research knowledge into health products and services. Gender equity and involvement of young scientists in this implementation process are other key goals of the PerMediNA project. In this paper, we are describing PerMediNA as the first PM implementation initiative in North Africa. Such initiatives contribute significantly in shortening existing health disparities and inequities between developed and developing countries and accelerate access to innovative treatments for global health.