Nouha Daoud

Targeted Therapies in HER2-Overexpressing Metastatic Breast Cancer

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.

Tumor location impact in stage II and III colon cancer: epidemiological and outcome evaluation

Background We aimed to describe clinico-pathological characteristics and differences between right-sided (RCC) and left-sided colon cancer (LCC) in Tunisian population. We also analyzed outcome to determine whether location is of prognostic significance. Methods Clinico-pathological characteristics and Kaplan Meier survival were compared between two groups of LCC [150] and RCC [53] patients with stage II and III adenocarcinoma treated with curative intent between 2003-2014. Results RCC patients were significantly more likely to be female, (56.6% vs. 39.3%, P=0.029) and to have undifferentiated tumor (87.1% vs. 8.4%, P=0.014), then LCC. After a median follow up of 49 months, 5-year overall survival (OS) was significantly worse in RCC vs. LCC [42% vs. 78%; hazard ratio (HR) =2.07; 95% CI: 1.05-4.09; P=0.03], no difference in relapse free survival (RFS) was observed. Median time to relapse was significantly shorter in RCC (15 months) vs. LCC (24 months), P=0.005. Tumor location significantly impacted survival in stage III, 5-year OS was 45% in RCC, and 63% in LCC, (HR =2.28; 95% CI: 1.01-5.24; P=0.04), there was no impact of tumor location in stage II, (HR =1.94; 95% CI: 0.54-6.93; P=0.29). Conclusions Prognostic impact of tumor location should be considered as a stratification factor in the future clinical trials.

Family specific genetic predisposition to breast cancer: results from Tunisian whole exome sequenced breast cancer cases

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.

Brain metastases epidemiology in a Tunisian population: trends and outcome

Aim: We reported anatomo-clinical features of brain metastases (BMs) collected in a Tunisian medical oncology department. Patients & methods: We retrospectively identified all cases of BM within a cohort of 7055 patients, treated for a histologically confirmed nonhematological cancer between 2000 and 2016. Data about age, sex and primary tumor were collected. Results: Incidence was 1.9% and mean age was 54 years with a 1.24 sex ratio. BMs were symptomatic in 73.7% of cases after a median time of 16 months. A total of 73.4% patients receiving local therapy, 88% by whole brain radiation therapy and 21.6% had a metastasectomy. Lung and breast cancers were the primary in 80% of the BM. Conclusion: BM showed trends of young with underestimated incidence.