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BackgroundA family history of breast cancer has long been thought to indicate the presence of inherited genetic events that predispose to this disease. In North Africa, many specific epidemio-genetic characteristics have been observed in breast cancer families when compared to Western populations. Despite these specificities, the majority of breast cancer genetics studies performed in North Africa remain restricted to the investigation of the BRCA1 and BRCA2 genes. Thus, comprehensive data at a whole exome or whole genome level from local patients are lacking.MethodsA whole exome sequencing (WES) of seven breast cancer Tunisian families have been performed using a family-based approach. We focused our analysis on BC-TN-F001 family that included two affected members that have been sequenced using WES. Relevant variants identified in BC-TN-F001 have been confirmed using Sanger sequencing. Then, we conducted an integrative analysis by combining our results with those from other WES studies in order to figure out the genetic transmission model of the newly identified genes. Biological network construction and protein–protein interactions analyses have been performed to decipher the molecular mechanisms likely accounting for the role of these genes in breast cancer risk.ResultsSequencing, filtering strategies, and validation analysis have been achieved. For BC-TN-F001, no deleterious mutations have been identified on known breast cancer genes. However, 373 heterozygous, exonic and rare variants have been identified on other candidate genes. After applying several filters, 12 relevant high-risk variants have been selected. Our results showed that these variants seem to be inherited in a family specific model. This hypothesis has been confirmed following a thorough analysis of the reported WES studies. Enriched biological process and protein–protein interaction networks resulted in the identification of four novel breast cancer candidate genes namely MMS19, DNAH3, POLK and KATB6.ConclusionsIn this first WES application on Tunisian breast cancer patients, we highlighted the impact of next generation sequencing technologies in the identification of novel breast cancer candidate genes which may bring new insights into the biological mechanisms of breast carcinogenesis. Our findings showed that the breast cancer predisposition in non-BRCA families may be ethnic and/or family specific.Electronic supplementary materialThe online version of this article (10.1186/s12967-018-1504-9) contains supplementary material, which is available to authorized users.

Human epidermal growth factor receptor-2 (HER2) is amplified in 25-30% of breast cancers and is associated with aggressive disease and poorer survival. Multiple anti-HER2 targeted therapies have dramatically changed management and outcome of this subgroup, both in adjuvant and metastatic settings. Despite the improvement of survival thanks to trastuzumab, unclear mechanisms of resistance occur, which has led to the development of new anti-HER2 therapies such as lapatinib, pertuzumab, and trastuzumab emtansine (T-DM1). The optimal sequence of the available drugs is still not well established. All this progress raises the question of toxicity that need to be managed, especially with longer survival of patients. In this article, we review different anti-HER2 therapies used in HER2-positive m etastatic breast cancer.

Prognostic impact of tumor location should be considered as a stratification factor in the future clinical trials.

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BackgroundBreast 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.MethodsA 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.ResultsIn 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.ConclusionOur 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.

Objectives: Primary cardiac tumors are rare and account for 0.001 to 0.03% of cardiac lesions. The authors aim to describe the clinical, the microscopic and the therapeutic characteristics of these tumors through a 13-year-experience in order to highlight the diagnostic challenges faced. Methods: We report 10 primary cardiac tumors diagnosed in the Departments of Pathology and Thoracic Surgery of the same hospital through a 13-year-period. Results: Our study was conducted on 7 women and 3 men. The mean age of the patients was 54.22 years (average, 12 to 79 years). Dyspnea represented the most frequent symptom. Physical examination was normal in all patients. Trans-thoracic ultra-sound examination was performed in all patients. Cardiac MRI allowed localizing the tumors in 2 patients. They were located into the left auricle (6 cases), the right auricle (1 case) and the pericardium (3 cases). The microscopic examination was concluded to myxoma (7 cases), haemangioma (2 cases) and hemangioendothelioma (1 case). Surgical resection was possible in 9 patients. It was impossible in the case of hemangioendothelioma because of the adherence. One death was recorded secondary to postoperative arrhythmia. The other patients presented no complications after a follow-up period ranging from 2 months to 5 years. Conclusion: Cardiac tumors are challenging in their diagnosis and management. A positive diagnosis is based on microscopic examination. Surgical treatment plays a key role and is possible in the majority of benign tumors. The prognosis of malignant tumors remains poor even if a complete surgical resection is possible.

Aim: We aimed to identify a cutoff value of tumor size (TuS) correlated to prognosis of stage II and III colorectal cancer and to evaluate the prognostic significance. Patients & methods: We retrospectively analyzed 257 patients treated for stage II–III colorectal cancer between 2003 and 2014. We used receiver-operating characteristic to evaluate TuS performance accuracy to predict survival. We identified a cutoff value. We used the Kaplan–Meier method and Cox regression analysis to study survival and prognostic factors. Results: Area under the receiver-operating characteristic curve of TuS was 0.62 ± 0.048. A size of 4 cm was identified as a predictor of survival with a sensitivity of 88.2% and a specificity of 59.2%. We observed 98 patients with TuS ≤4 cm and 159 patients with TuS greater than 4 cm. Patients with TuS greater than 4 cm were more likely to have a cancer located in the colon (81.1 vs 70.4%, p = 0.002) and commonly pT4 (44 vs 22.4%, p = 0.0001). There was no difference in terms of gender, insufficient removed lymph nodes number, number of positive lymph nodes, stage and oxaliplatin administration between both groups. 5-year survival rate of patients with TuS ≥4 cm and TuS less than 4 cm was 76 and 84%, respectively (p = 0.008). Age ≥65 years, stage III, venous invasion and pN+ greater than 3 were significant bad prognostic factors in patients with TuS ≥4 cm in univariate analysis. Stage III was the only independent prognostic factor in multivariate analysis. Administration of chemotherapy was the only factor with significant impact on survival in univariate and multivariate analyses in patients with TuS less than 4 cm. Conclusion: TuS had not only an impact on survival but also interfered with other prognostic factors.