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.

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.

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.

Obesity and cancer: focus on leptin.

Over the past decades, obesity has grown to epidemic proportions worldwide. It has been associated with an increased risk for different types of cancer. In addition, obesity has been associated with a poor prognosis, an increased risk of metastasis and mortality, and resistance to anti-cancer therapies. The pathophysiological mechanisms underlying the obesity-cancer connection have not yet been fully elucidated. However, this connection could result, at least in part, from the action of adipokines, whose levels are increased in obesity. Among these adipokines, evidence suggests leptin's critical role in linking obesity to cancer. In this review, we first summarize the current state of the literature regarding the implication of leptin in tumorigenic processes. Next, we focus on the effects of leptin on the anti-tumor immune response. Then, we discuss the influence of leptin on the efficiency of antineoplastic treatments and the development of tumor resistance. Finally, we highlight the use of leptin as a potential target for the prevention and treatment of cancer.

MARCKS as a Potential Therapeutic Target in Inflammatory Breast Cancer.

Inflammatory breast cancer (IBC) is the most pro-metastatic form of breast cancer (BC). We previously demonstrated that protein overexpression of Myristoylated Alanine-Rich C Kinase Substrate (MARCKS) protein was associated with shorter survival in IBC patients. MARCKS has been associated with the PI3K/AKT pathway. MARCKS inhibitors are in development. Our objective was to investigate MARCKS, expressed preferentially in IBC that non-IBC (nIBC), as a novel potential therapeutic target for IBC. The biologic activity of MPS, a MARCKS peptide inhibitor, on cell proliferation, migration, invasion, and mammosphere formation was evaluated in IBC (SUM149 and SUM190) and nIBC (MDA-MB-231 and MCF7) cell lines, as well as its effects on protein expression in the PTEN/AKT and MAPK pathways. The prognostic relevance of MARCKS and phosphatase and tensin homolog (PTEN) protein expression as a surrogate marker of metastasis-free survival (MFS) was evaluated by immunohistochemistry (IHC) in a retrospective series of archival tumor samples derived from 180 IBC patients and 355 nIBC patients. In vitro MPS impaired cell proliferation, migration and invasion, and mammosphere formation in IBC cells. MARCKS inhibition upregulated PTEN and downregulated pAKT and pMAPK expression in IBC cells, but not in nIBC cells. By IHC, MARCKS expression and PTEN expression were negatively correlated in IBC samples and were associated with shorter MFS and longer MFS, respectively, in multivariate analysis. The combination of MARCKS-/PTEN+ protein status was associated with longer MFS in IBC patient only (p = 8.7 × 10-3), and mirrored the molecular profile (MARCKS-downregulated/PTEN-upregulated) of MPS-treated IBC cell lines. In conclusion, our results uncover a functional role of MARCKS implicated in IBC aggressiveness. Associated with the good-prognosis value of the MARCKS-/PTEN+ protein status that mirrors the molecular profile of MPS-treated IBC cell lines, our results suggest that MARCKS could be a potential therapeutic target in patients with MARCKS-positive IBC. Future preclinical studies using a larger panel of IBC cell lines, animal models and analysis of a larger series of clinical samples are warranted in order to validate our results.

Association between epidemiological and clinico-pathological features of breast cancer with prognosis, family history, Ki-67 proliferation index and survival in Tunisian breast cancer patients.

Breast cancer has different epidemio-clinical characteristics in Middle East and North-African populations compared to those reported in the Western countries. The aim of this study is to analyze the epidemiological and clinico-pathological features of breast cancer in Tunisia and to determine prognostic factors with special interest to family history, Ki-67 proliferation index and comorbidity. We retrospectively reviewed epidemiological and clinico-pathological data from patients' medical records, treated in the Medical Oncology Department at Abderrahmane Mami Hospital, in the period 2011-2015. Data has been collected on 602 breast cancer patients and analyzed using SPSS software V.23.0. Our study showed high fractions of young breast cancer patients and cases with dense breasts. The most prevalent comorbidities observed in the studied cohort were cardiovascular diseases and diabetes. Familial breast cancer was found in 23.3% of cases and was associated with younger age at diagnosis (p<0.001) and advanced stage (p = 0.015). Ki-67 index >20% was significantly associated with early age at diagnosis, lymph node involvement (p = 0.002), advanced tumor grade (p<0.001) and high risk of relapse (p = 0.007). Ki-67 cut-off 30% predicted survival in luminal cases. Survival was worse in patients with triple negative breast cancer compared to non-triple negative breast cancer, inflammatory breast cancer compared to non-inflammatory breast cancer, moderately to poorly differentiated tumors compared to well-differentiated tumors and with positive lymph nodes compared to pN0 (p<0.05). Our study showed new insights into epidemiological and clinico-pathological characteristics of breast cancer that are not well explored in Tunisian population. Considering our findings along with the implementation of electronic health record system may improve patient health care quality and disease management.

Cognitive complaints during breast cancer endocrine therapy: aromatase inhibitors versus tamoxifen.

OBJECTIVE: Previous data hypothesise that women receiving aromatase inhibitors (AIs) exhibit worse cognitive functioning than patients on tamoxifen (TAM) since their oestrogen levels are lower. We aimed to compare cognitive complaints in both groups. METHODS: From September 2020 to January 2021, we conducted a cross-sectional study on patients with stage I-III breast cancer undergoing adjuvant endocrine therapy for at least 6 months. Cognitive complaints were assessed using the Functional Assessment of Cancer Therapy-Cognitive V.3 questionnaire with higher scores indicating better outcomes. RESULTS: We included 108 female patients, 60 on AI and 48 on TAM. Mean age at diagnosis was 52 (44 in the TAM group vs 58 in the AI group, p<0.001). Assessment of 'perceived cognitive impairment-20 subscale' did not identify a significant difference between the two groups (mean score: patients on AI=63/80 vs patients on TAM=58/80, p=0.198). Patients on TAM scored significantly worse than patients on AI (p<0.001) on the concentration complaints, while for the verbal domain, memory, multitasking, speed and functional interference, no significant difference between the two groups was observed. The difference in concentration complaints was maintained after adjustment to age, educational level, physical activity, prior exposure to chemotherapy, and living alone or with others. Finally, a favourable impact of regular physical activity on concentration scores was observed in both groups (p<0.001). CONCLUSION: Despite age difference, patients on AI did not demonstrate worse complaints than patients on TAM. Patients on TAM exhibited significantly increased concentration complaints. Oncologists should carefully screen their patients for mental fog and educate them on the importance of regular exercise.

Health influenced by genetics: A first comprehensive analysis of breast cancer high and moderate penetrance susceptibility genes in the Tunisian population.

Significant advances have been made to understand the genetic basis of breast cancer. High, moderate and low penetrance variants have been identified with inter-ethnic variability in mutation frequency and spectrum. Genome wide association studies (GWAS) are widely used to identify disease-associated SNPs. Understanding the functional impact of these risk-SNPs will help the translation of GWAS findings into clinical interventions. Here we aim to characterize the genetic patterns of high and moderate penetrance breast cancer susceptibility genes and to assess the functional impact of non-coding SNPs. We analyzed BRCA1/2, PTEN, STK11, TP53, ATM, BRIP1, CHEK2 and PALB2 genotype data obtained from 135 healthy participants genotyped using Affymetrix Genome-Wide Human SNP-Array 6.0. Haplotype analysis was performed using Haploview.V4.2 and PHASE.V2.1. Population structure and genetic differentiation were assessed using principal component analysis (PCA) and fixation index (FST). Functional annotation was performed using In Silico web-based tools including RegulomeDB and VARAdb. Haplotype analysis showed distinct LD patterns with high levels of recombination and haplotype blocks of moderate to small size. Our findings revealed also that the Tunisian population tends to have a mixed origin with European, South Asian and Mexican footprints. Functional annotation allowed the selection of 28 putative regulatory variants. Of special interest were BRCA1_ rs8176318 predicted to alter the binding sites of a tumor suppressor miRNA hsa-miR-149 and PALB2_ rs120963 located in tumorigenesis-associated enhancer and predicted to strongly affect the binding of P53. Significant differences in allele frequencies were observed with populations of African and European ancestries for rs8176318 and rs120963 respectively. Our findings will help to better understand the genetic basis of breast cancer by guiding upcoming genome wide studies in the Tunisian population. Putative functional SNPs may be used to develop an efficient polygenic risk score to predict breast cancer risk leading to better disease prevention and management.

Docetaxel monotherapy induces necrotic acute pancreatitis.

INTRODUCTION: Drug-induced acute pancreatitis (AP) is uncommon and represents 0.1 to 2% of all AP cases. Chemotherapy-induced AP is very rare. Docetaxel monotherapy-induced AP has been reported only once in the literature. Herein we report the second case of docetaxel-related AP and the first case of necrotic AP induced by this agent. CASE REPORT: We describe the case of a severe docetaxel-induced AP classified as stage E Balthazar in a 55-year-old female treated with adjuvant docetaxel for localized breast cancer. Symptoms occurred five hours following the first infusion of docetaxel. MANAGEMENT AND OUTCOME: The patient was hospitalized for 15 days for appropriate management. According to the CTCAE (Common Terminology Criteria for Adverse Events) version 5.0 this was a grade 4 toxicity and chemotherapy was withdrawn thereafter. Drug rechallenge was not possible because of the severity of the presentation. DISCUSSION: Medical oncologists should be aware that docetaxel may induce severe pancreatitis. Therefore, they should prompt testing of serum lipase when patients consult for unusual abdominal pain following chemotherapy infusion. Recognizing this entity is paramount to allow early and appropriate management.

Prognostic impact of tumor-infiltrating lymphocytes in non-small cell lung carcinomas.

INTRODUCTION: Tumor-infiltrating lymphocytes represent a pivotal component of the host anti-tumor response. Thus, they considerably influence the evolution of cancers including non-small cell lung carcinomas. Even if, this important role is consensual, many discordant results are published in the literature about the prognostic role of the different populations of tumor-infiltrating lymphocytes. The aim of our work was to evaluate the prognostic impact of CD8+, CD4+, and forkhead box protein P3+ lymphocytes in the tumor microenvironment of non-small cell lung carcinomas. METHODS: We conducted a retrospective descriptive study, which included non-small cell lung carcinomas diagnosed in the department of pathology and followed in the medical oncology department of the same hospital between 2011 and 2015. Tumor-infiltrating lymphocytes were analyzed by the immunohistochemical method for forkhead box protein P3, CD4, and CD8. Intratumoral and stromal-labeled lymphocytes were quantified by manual counting at high magnification (×400). Forkhead box protein P3+/CD8+, forkhead box protein P3+/CD4+, and CD8+/CD4+ ratios were subsequently calculated. The prognostic value of tumor-infiltrating lymphocytes was assessed in respect of overall survival, recurrence-free survival, and relapse-free survival. RESULTS: Thirty-nine patients were included. The mean age of patients was 59.6 years. A complete surgical resection (p = 0.009), and a CD8/CD4 ratio (p = 0.008) were prognostic factors for overall survival. Complete surgical resection (p = 0.003), the forkhead box protein P3/CD8 (p = 0.005), and forkhead box protein P3/CD4 (p = 0.037) ratios were prognostic factors for recurrence-free survival. The CD8+ tumor-infiltrating lymphocytes rate (p = 0.037) was a prognostic factor for relapse-free survival with a threshold of 67.8/high power field. Microscopic subtype (p = 0.037) was a prognostic factor for relapse-free survival when only adenocarcinoma and squamous cell carcinoma were considered. In multivariate analysis, age (p = 0.004) and a CD8/CD4 ratio (p = 0.016) were independent predictors of overall survival. CONCLUSION: Despite the limitations of our study, our results confirm the prognostic value of tumor-infiltrating lymphocytes in non-small cell lung carcinomas and the importance of the combined quantification of their different subpopulations.

Understanding COVID-19 vaccine hesitancy and resistance: another challenge in cancer patients.

INTRODUCTION: We aimed to measure the acceptability towards the COVID-19 vaccination in cancer patients and to investigate determinant factors associated with the patient's choice. METHODS: We conducted a cross-sectional survey with a self-administered questionnaire delivered to 329 cancer patients in 3 oncology cancer centers in Tunisia between February-May 2021. Logistic regression was used to evaluate odds ratio predicting patient's intentions toward the vaccine. RESULTS: Acceptance rate was 50.5%, 28.3% (n = 93) reported to definitely refuse the vaccine and 21.2% (n = 70) did not make their decision yet. High educational level, history of comorbidities, history of influenza vaccination in the current season, and patient's opinion about the severity of COVID-19 did not predict vaccine resistance. However, patients who think that the vaccine may interfere with treatment efficacy (OR = 7.28, 95%CI [2.5-12.32]), or may impact cancer outcome (OR = 6.14, 95%CI [2.27-16.7]), were significantly more likely to refuse the vaccine. Patients who disagree that the vaccine is a major weapon against the pandemic (OR = 6.07, 95%CI [2.34-9.52]) or that it could reduce the virus transmission (OR = 7.34, 95%CI [4.22-11.81]) were also significantly more likely to reject the vaccination. Safety concerns were also significant predictive factors (OR = 7.9, 95%CI [4.10-11.27]. Confidence level in the authorities played a significant role in patient's acceptance of the vaccine, indeed patients who are not registered (OR = 5.9, 95%CI [1.58-8.7]) or not informed about the Tunisian national vaccination platform EVAX (OR = 5.51, 95%CI [2.1-7.9]) were more likely to be against the vaccine. CONCLUSION: Cancer patient's education about the impact of the vaccine on their disease and on the COVID-19 is needed. Governments should build strategies to gain more population confidence.

Translation and Validation of the Comprehensive Score of Financial Toxicity for Cancer Patients Into Arabic.

Background and Purpose: We aimed to translate the Comprehensive Score of Financial Toxicity (COST) questionnaire into Arabic and to evaluate its reliability and validity. Methods: We applied the four-step translation method and conducted a pilot validation study over 179 medical oncology patients. Reliability was tested using the Cronbach alpha coefficient and test-retest stability. Validity was tested using the correlation with Functional assessment of Cancer Therapy-General score (FACT-G), factorial analysis and the content validity index. Results: Questionnaire showed high internal consistency and test retest reliability; Cronbach alpha coefficient was 0.77 and Pearson stability coefficient was 0.8. Convergent validity evaluation showed a statistically significant moderate correlation with the FACT-G (r = .42, p =.047). Content validly index was 0.93. Conclusions: The Arabic version of COST questionnaire, was a valid and reliable tool that could be used in clinical practice by healthcare providers to evaluate financial toxicity in Arab speaking cancer patients.

Identification of Eleven Novel BRCA Mutations in Tunisia: Impact on the Clinical Management of BRCA Related Cancers.

BACKGROUND: Breast cancer is the world's most common cancer among women. It is becoming an increasingly urgent problem in low- and middle-income countries (LMICs) where a large fraction of women is diagnosed with advanced-stage disease and have no access to treatment or basic palliative care. About 5-10% of all breast cancers can be attributed to hereditary genetic components and up to 25% of familial cases are due to mutations in BRCA1/2 genes. Since their discovery in 1994 and 1995, as few as 18 mutations have been identified in BRCA genes in the Tunisian population. The aim of this study is to identify additional BRCA mutations, to estimate their contribution to the hereditary breast and ovarian cancers in Tunisia and to investigate the clinicopathological signatures associated with BRCA mutations. METHODS: A total of 354 patients diagnosed with breast and ovarian cancers, including 5 male breast cancer cases, have been investigated for BRCA1/2 mutations using traditional and/or next generation sequencing technologies. Clinicopathological signatures associated with BRCA mutations have also been investigated. RESULTS: In the current study, 16 distinct mutations were detected: 10 in BRCA1 and 6 in BRCA2, of which 11 are described for the first time in Tunisia including 3 variations that have not been reported previously in public databases namely BRCA1_c.915T>A; BRCA2_c.-227-?_7805+? and BRCA2_c.249delG. Early age at onset, family history of ovarian cancer and high tumor grade were significantly associated with BRCA status. BRCA1 carriers were more likely to be triple negative breast cancer compared to BRCA2 carriers. A relatively high frequency of contralateral breast cancer and ovarian cancer occurrence was observed among BRCA carriers and was more frequent in patients carrying BRCA1 mutations. CONCLUSION: Our study provides new insights into breast and ovarian cancer genetic landscape in the under-represented North African populations. The prevalence assessment of novel and recurrent BRCA1/2 pathogenic mutations will enhance the use of personalized treatment and precise screening strategies by both affected and unaffected North African cancer cases.

Identification of BRCA2 Cis Double Heterozygous Breast Cancer Cases Using Whole Exome Sequencing: Phenotypic Expression and Impact on Personalized Oncology.

BRCA1 and BRCA2 are the most commonly mutated breast cancer susceptibility genes that convey a high risk of breast and ovarian cancer. Most BRCA1 or BRCA2 mutation carriers have inherited a single heterozygous mutation. In recent years, very rare cases with biallelic or trans double heterozygous mutations on BRCA1 and or BRCA2 have been identified and seem to be associated with distinctive phenotypes. Given that this genotype-phenotype correlation in cancer predisposing hereditary conditions is of relevance for oncological prevention and genetic testing, it is important to investigate these rare BRCA genotypes for better clinical management of BRCA mutation carriers. Here we present the first report on Cis double heterozygosity (Cis DH) on BRCA2 gene identified using Whole exome sequencing (WES) in a Tunisian family with two BRCA2 mutations namely: c.632-1G>A and c.1310_1313DelAAGA that are both reported as pathogenic in ClinVar database. Subsequent analysis in 300 high-risk Tunisian breast cancer families detected this Cis double heterozygous genotype in 8 additional individuals belonging to 5 families from the same geographic origin suggesting a founder effect. Moreover, the observed Cis DH seems to be associated with an early age of onset (mean age = 35.33 years) and severe phenotype of the disease with high breast cancer grade and multiple cancer cases in the family. The identification of unusual BRCA genotypes in this Tunisian cohort highlights the importance of performing genetic studies in under-investigated populations. This will also potentially help avoiding erroneous classifications of genetic variants in African population and therefore avoiding clinical misdiagnosis of BRCA related cancers. Our findings will also have an impact on the genetic testing and the clinical management of North African breast cancer patients as well as patients from different other ethnic groups in regard to several emerging target therapies such as PARP inhibitors.

Response to Induction Neoadjuvant Hormonal Therapy Using Upfront 21-Gene Breast Recurrence Score Assay-Results From the SAFIA Phase III Trial.

PURPOSE: Luminal, human epidermal growth factor receptor 2-negative breast cancer represents the most common subtype of breast malignancies. Neoadjuvant strategies of operable breast cancer are mostly based on chemotherapy, whereas it is not completely understood which patients might benefit from neoadjuvant hormone therapy (NAHT). MATERIALS AND METHODS: The SAFIA trial is a prospective multicenter, international, double-blind, neoadjuvant phase III trial, using upfront 21-gene Oncotype DX Breast Recurrence Score assay (recurrence score [RS] < 31) to select operable luminal human epidermal growth factor receptor 2-negative patients, for induction hormonal therapy HT (fulvestrant 500 mg with or without goserelin) before randomly assigning responding patients to fulvestrant 500 mg (with or without goserelin) plus either palbociclib (cyclin-dependent kinase 4/6 inhibitor) or placebo. The objectives of this interim analysis were to assess the feasibility of upfront RS determination on core biopsies in the Middle-East and North Africa region and evaluate the efficacy of induction NAHT in patients with an RS < 31. RESULTS: At the time of this interim analysis, 258 patients with relative risk were accrued, including 202 patients (RS < 31% to 78.3%) treated with induction NAHT and 182 patients evaluable so far for response. The feasibility of performing the Oncotype DX assays on core biopsy specimens was optimal in 96.4% of cases. Overall, 93.4% of patients showed hormone sensitivity and no difference in NAHT efficacy was noticed between RS 0-10, 11-25, and 26-30. Interestingly, patients with high RS (26-30) showed a trend toward a higher major response rate (P = .05). CONCLUSION: The upfront 21-gene assay performed on biopsies is feasible in our population and has allowed us to select patients with high hormone sensitivity (RS < 31). This approach could be an alternative to upfront surgery without significant risk of progression, particularly during pandemic times.

Amenorrhea and elevated ßhuman chorionic gonadotropin of unknown origin: An unexpected location of choriocarcinoma.

Choriocarcinoma is a rare malignancy originating from trophoblastic cells that is known to arise from the placenta. In this report, we describe the case of a 28-year-old female who consulted for amenorrhea and elevated ßhCG mimicking a pregnancy of an unknown location, which ultimately turned out to be primary choriocarcinoma of the lung.

Germline copy number variations in BRCA1/2 negative families: Role in the molecular etiology of hereditary breast cancer in Tunisia.

Hereditary breast cancer accounts for 5-10% of all breast cancer cases. So far, known genetic risk factors account for only 50% of the breast cancer genetic component and almost a quarter of hereditary cases are carriers of pathogenic mutations in BRCA1/2 genes. Hence, the genetic basis for a significant fraction of familial cases remains unsolved. This missing heritability may be explained in part by Copy Number Variations (CNVs). We herein aimed to evaluate the contribution of CNVs to hereditary breast cancer in Tunisia. Whole exome sequencing was performed for 9 BRCA negative cases with a strong family history of breast cancer and 10 matched controls. CNVs were called using the ExomeDepth R-package and investigated by pathway analysis and web-based bioinformatic tools. Overall, 483 CNVs have been identified in breast cancer patients. Rare CNVs affecting cancer genes were detected, of special interest were those disrupting APC2, POU5F1, DOCK8, KANSL1, TMTC3 and the mismatch repair gene PMS2. In addition, common CNVs known to be associated with breast cancer risk have also been identified including CNVs on APOBECA/B, UGT2B17 and GSTT1 genes. Whereas those disrupting SULT1A1 and UGT2B15 seem to correlate with good clinical response to tamoxifen. Our study revealed new insights regarding CNVs and breast cancer risk in the Tunisian population. These findings suggest that rare and common CNVs may contribute to disease susceptibility. Those affecting mismatch repair genes are of interest and require additional attention since it may help to select candidates for immunotherapy leading to better outcomes.

Assessing the financial toxicity in Tunisian cancer patients using the Comprehensive Score for Financial Toxicity (COST).

BACKGROUND: Cancer care-related out-of-pocket expenses and financial toxicity (FT) are a rising burden for patients. We aimed to evaluate patient-reported FT and to identify relevant correlates within a Tunisian population. METHODS: We conducted a survey using the 11-item Comprehensive Score for Financial Toxicity (COST) that could range from 0 = high to 44 = low. FT was grade 0 if ≥ 26, grade 1 = (14-25), grade 2 = (1-13), and grade 3 = 0. Scores were collected along with data regarding patient medical/social features and out-of-pocket expenses. Univariate and multivariate analyses were performed to identify factors associated with higher financial burden. RESULTS: Among the 179 participants, median COST score was 20.8 (Q1 17-Q3 24), with 80.4% of patients experiencing financial toxicity: grade 0 = 20%, grade 1 = 68.4%, grade 2 = 11.7%, grade 3 = 0%. Most patients (66.5%) used to work before cancer and 44.7% reported ceasing work because of cancer. The time to go to the hospital was > 30 min in 66.5% of cases. Unemployment, time to hospital > 30 min, ceasing work because of cancer, and expenses on non-chemotherapy drugs exceeding 70 dinars (25 US dollars) were mostly associated with higher FT on univariate analysis. Distance to hospital and ceasing work because of cancer were the single most significant factors in multivariate analysis. CONCLUSIONS: Losing work due to cancer and unequal distribution of health care particularly in cities with long travel times to the nearest hospital are the main sources of financial distress.