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Recent discovery showing the presence of microRNAs (miRNAs) in the circulation sparked interest in their use as potential biomarkers. Our previous studies showed the diagnostic potential of miR-451 as a serological marker for inflammatory breast cancer (IBC), miR-337- 5p and miR-30b for non-inflammatory breast cancer (non-IBC). The aim of this study is to investigate the prognostic values of circulating miRNAs by comparing the amounts of 12 circulating miRNAs in the serum of IBC and non-IBC from Tunisian breast cancer patients, and by determinating whether correlated pairs of miRNAs could provide useful information in the diagnosis of IBC and non-IBC patients. TaqMan qPCR was performed to detect circulating expression of miRNAs in serum of 20 IBC, 20 non-IBC and 20 healthy controls. Nonparametric rank Spearman rho correlation coefficient was used to examine the prognostic value of miRNAs and to assess the correlation profile between miRNAs expression. Further, a large number of miRNAs were highly correlated (rho>0.5) in both patients groups and controls. Also, the correlations profiles were different between IBC, non-IBC and healthy controls indicating important changes in molecular pathways in cancer cells. Our results showed that miR-335 was significantly overexpressed in premenopausal non-IBC patients; miR-24 was significantly overexpressed in non-IBC postmenopausal patients. Patients with previous parity had higher serum of miR-342-5p levels than those without. Furthermore, patients with HER2+ IBC present lower serum levels of miR-15a than patients with HER2- disease. Together, these results underline the potential of miRNAs to function as diagnostic and prognostic markers for IBC and non-IBC, with links to the menopausal state, Her2 status and parity.

Background To reduce tobacco smoking is, in Tunisia, a public health priority. The tobacco cessation consultation is one of the interventions to fight against the tobacco epidemic; it is a new activity developed in the Salah-Azeiz Tunis cancer centre. The objective of this work is to evaluate the impact of the consultation on the smokers after one year of activities and to analyse the prognostic factors of tobacco cessation in order to improve the efficacy of such an activity in the future, in Tunisia. Methods The cessation methods were based on cognitive and behavioral therapies associated with nicotine patch, delivered free of charge. During one year (July 2003 to June 2004), 340 smokers were attended. Data on their smoking status and psychological characteristics were collected using a standardized questionnaire. Results The patients were mostly men (79%), these smokers did not present important anxiodepressive troubles, 68% thought that they were able to quit easily. The majority (57%) smoked more than 20 cigarettes a day and was nicotinodependant (Fagenstrom > 7). Half of this population had already intended to stop, they declared to smoke mostly because of stress. The global cessation rate after a median follow-up of 32 weeks is 27%. The cessation rate lasting six months for 83 patients followed regularly was 23%. The good prognostic factors of cessation, after multivariate analysis, were (when taking out from the model the regular follow-up), to be confidant on the possibility to stop (OR = 0.87 [0.78–0.97]). On the contrary, a high score (>7) for Fagerstrom test (OR = 1.9 [1.1–3.4), the use of smoking to fight against stress (OR = 1.08 [1.0–1.2) and a smoking environment at home (OR = 4.5 [1.1–18.9]) were prognostic of a failure in quitting smoking. Conclusion These results show that the cessation rate, which is still too low as compared with the literature, could be increased by a better follow-up of smokers associated with an information campaign on the existing possibilities to quit smoking in Tunisia.

This study aimed to identify prognostic factors for outcome in Tunisian patients with nonmetastatic inflammatory breast cancer (IBC) receiving multimodality therapy.From 1994 to 2000, 100 patients with nonmetastatic IBC were reviewed. Patients underwent neo-adjuvant chemotherapy including anthracyclines (99%), then mastectomy (93%) when feasible, radiotherapy (83%) and adjuvant chemotherapy (84%). Sixty patients (60%) had hormone therapy.Median age at diagnosis was 44 years (range 23-71). Seventy patients had premenopausal status (70%). Ten cases occurred during pregnancy (10%). Body mass index indicated overweight or obesity in 76 patients (76%). After neo-adjuvant chemotherapy, pathologic complete response (pCR) rate was 20%. Median time of follow-up for surviving patients was 44 months. Median progression-free survival (PFS) was 19 months and overall survival (OS) 30 months. Factors associated with improved survival were no pregnancy (P = 0.0095), estrogen receptor positivity (P = 0.028), tumor size5 cm (P = 0.021), clinical complete response (cCR) (P = 0.022), pCR (P = 0.011), negative nodes (P = 0.053) and hormone therapy (P0.001). In multivariate analysis, cCR, negative nodes and hormone therapy were independently associated with better OS and PFS. Factors predictive to pCR were age45 years, negative nodes and cCR.Tunisian patients with IBC have particular epidemiologic characteristics, with earlier disease and context of overweight and obesity, but prognostic factors are similar to those reported in the literature. Hormone therapy seems to improve patient outcome.

Breast cancer, the most commonly diagnosed cancer in women, is the second leading cause of cancer death in women worldwide. To investigate the contribution of BRCA1 gene mutations to familial breast cancer in Tunisia, 32 unrelated patients who had at least one first degree relative affected with breast and/or ovarian cancer were analysed. BRCA1 mutation analysis was performed by DNA sequencing of all BRCA1 exons. We identified four different BRCA1 frameshift mutations: c. 4041delAG, c. 2551delG and c. 5266dupC already been described and one novel mutation, c. 211dupA, observed in two unrelated families. C. 5266dupC has previously been found among Jewish Ashkenazi and Eastern European populations. Our study describes it in Arabic/Berber population. Five out of thirty two familial cases had deleterious BRCA1 mutations. Fifteen additional cases carried unclassified variants (UV) or single nucleotide polymorphisms (SNPs). Our study is the first molecular investigation on the role of BRCA1 in hereditary breast cancer in North Tunisia.

Hereditary breast cancer accounts for 3-8% of all breast cancers, with mutations in the BRCA1 and BRCA2 genes responsible for up to 30% of these. To investigate the prevalence of BRCA1 and BRCA2 gene mutations in breast cancer patients with affected relatives in Tunisia, we studied 36 patients who had at least one first degree relative with breast and/or ovarian cancer Thirty-four 34 patients were suggestive of the BRCA1 mutation and two were suggestive of the BRCA2 mutation, based on the presence of male breast cancer detected in their corresponding pedigrees. Four mutations in BRCA1 were detected, including a novel frame-shift mutation (c.211dupA) in two unrelated patients and three other frameshift mutations - c.4041delAG, c.2551delG and c.5266dupC. Our study is the first to describe the c.5266dupC mutation in a non-Jewish Ashkenazi population. Two frameshift mutations (c.1309del4 and c.5682insA) were observed in BRCA2. Nineteen percent (7/36) of the familial cases had deleterious mutations of the BRCA1 or BRCA2 genes. Almost all patients with deleterious mutations of BRCA1 reported a family history of breast and/or ovarian cancer in the index case or in their relatives. Our data are the first to contribute to information on the mutation spectrum of BRCA genes in Tunisia, and we give a recommendation for improving clinical genetic testing policy.

Resume Le cancer du sein constitue la premiere pathologie maligne chez la femme tunisienne. Le delai entre le premier symptome et le diagnostic est souvent tres long, ce qui explique la predominance des tumeurs volumineuses et l'atteinte ganglionnaire frequente. Cette situation a ete exploitee pour l'analyse de la rupture de tolerance vis-a-vis de l'anti-oncogene p53. Notre etude a porte sur 108 patientes âgees de 23 a 67 ans, colligees au service de chimiotherapie de l'ISA (institut Salah-Azaiez de Tunis) du mois d'avril au mois de juillet 2002. Nous avons etudie l'alteration de la p53 dans le cancer du sein par deux approches : serologique (anticorps anti-p53 circulants) et immunohistochimique (accumulation intratumorale de la p53). Nos resultats montrent que la p53 est alteree dans environ 40 % des cancers mammaires. L'immunohistochimie positive correle avec le grade histologique eleve de la tumeur, alors que l'envahissement ganglionnaire ainsi que l'absence de recepteurs hormonaux sont associes a une serologie anti-p53 positive. La rupture de tolerance vis-a-vis de la p53 semble dependre de plusieurs facteurs ce qui implique que la serologie anti-p53 ne presente pas un interet diagnostique dans le cancer du sein pour les patientes tunisiennes.

Resume Les metastases dans la moelle epiniere sont extremement rares et surviennent chez 0,1 a 0,4 % des patients cancereux. Nous rapportons le cas de metastases intramedullaires survenant chez un patient de 42 ans, 12 mois apres le diagnostic initial d’un adenocarcinome du poumon. Le patient etait sous chimiotherapie de troisieme ligne pour une progression tumorale locale et metastatique ganglionnaire et osseuse. Le patient a consulte pour une faiblesse avec trouble de la marche. L’IRM a permis de retenir le diagnostic de metastases intramedullaires. Une radiotherapie sur la moelle associee a une corticotherapie a ete debutee. Un traitement par therapie ciblee a ete indique. Le patient est decede trois mois apres le debut du traitement. Notre objectif est de rapporter un nouveau cas de metastase dans la moelle epiniere d’un adenocarcinome pulmonaire en insistant sur sa rarete ainsi que ses difficultes diagnostiques et therapeutiques a travers une revue de la litterature.

It was previously shown that letrozole (Femara) was significantly more potent than anastrozole (Arimidex) in inhibiting aromatase activity in vitro and in inhibiting total body aromatisation in patients with breast cancer. The objective of this study was to compare letrozole (2.5 mg per day) and anastrozole (1 mg per day) as endocrine therapy in postmenopausal women with advanced breast cancer previously treated with an anti-oestrogen. This randomised, multicentre and multinational open-label phase IIIb/IV study enrolled 713 patients. Treatment was for advanced breast cancer that had progressed either during anti-oestrogen therapy or within 12 months of completing that therapy. Patients had tumours that were either positive for oestrogen and/or progesterone receptors (48%) or of unknown receptor status (52%). The primary efficacy endpoint was time to progression (TTP). Secondary endpoints included objective response, duration of response, rate and duration of overall clinical benefit (responses and long-term stable disease), time to treatment failure, and overall survival, as well as general safety. There was no difference between the treatment arms in TTP; median times were the same for both treatments. Letrozole was significantly superior to anastrozole in the overall response rate (ORR) (19.1% versus 12.3%, P=0.013), including in predefined subgroups (receptor status-unknown, and soft-tissue- and viscera-dominant site of disease). There were no significant differences between the treatment arms in the rate of clinical benefit, median duration of response, duration of clinical benefit, time to treatment failure or overall survival. Both agents were well tolerated and there were no significant differences in safety. These results support previous data documenting the greater aromatase-inhibiting activity of letrozole and indicate that advanced breast cancer is more responsive to letrozole than to anastrozole as second-line endocrine therapy.

Secondary tumours to radio- and/or chemotherapy have rarely been reported after treatment for head and neck cancers. We report a case of mandibular fibrosarcoma observed 7 years after chemoradiotherapy for undifferentiated nasopharyngeal carcinoma in a patient treated when 20 years old.

Resume Objectif : Evaluer notre experience a l’institut Salah Azaiz concernant la pose et le maniement des sites implantables en cancerologie medicale. Patients et methodes : De janvier 1992 a juin 2000, nous avons indique la pose de 208 voies veineuses centrales (VVC) par voie sous-claviere avec site d’injection sous-cutane chez 179 patients adultes (118F/61H) et 26 enfants (14F/12G) dont l’âge moyen etait de 37 ans (7 mois a 72 ans). Les indications etaient essentiellement celles d’une chimiotherapie de longue duree ou en perfusion continue ou vesicante pour metastases ou recidives de tumeurs du sein (93/179), cancer digestif (42/179) ou cancer pediatrique (26 cas). Resultats : En dehors de trois echecs initiaux, 205 SI ont ete poses chez 202 patients (double chez trois d’entre eux). La veine sous-claviere a ete ponctionnee par voie percutanee sus-claviculaire (voie de Yoffa) dans 156/205 cas et sous-claviculaire (voie d’Aubaniac) dans 32 cas, du cote gauche dans 153 cas et droit dans 52 cas. La conversion en jugulaire interne a ete effectuee chez 17 patients. Les incidents initiaux ont consiste en six ponctions arterielles (2,9 %), trois pneumothorax (1,5 %) et une migration de catheter dans l’artere pulmonaire droite. La duree mediane de maintien du materiel etait de 210 jours pour les adultes (3 a 1460 j) et de 185 jours pour les enfants (3 a 1100 j). La duree d’implantation a ete de 49 200 site-jours. Nous avons procede a l’explantation de 17 sites (8 %), pour infection (huit cas), ulceration cutanee (huit cas) ou extravasation d’actinomycine D (un cas), six cas (2,9 %) de thromboses veineuses sus-claviculaires et jugulaires ont ete traites par anticoagulants et attitude conservatrice du site. Actuellement, 58 patients sont vivants avec leur site en place. Conclusion : L’utilisation des catheters veineux centraux relies a un site implantable permet en general un maintien prolonge du materiel ameliorant ainsi le confort du patient et de l’equipe soignante. Le prix eleve de ce materiel est amorti apres une utilisation frequente et prolongee.

Since the few data exploring a possible association between Epstein–Barr virus (EBV) and breast cancer are conflicting, we investigated this association together with the influences of geographical areas. 509 breast cancers were sampled from areas with varying risks of nasopharynx carcinoma (NPC) such as North Africa (Algeria and Tunisia, high-risk area); southern France (Marseille, intermediate-risk area); and northern Europe (northern France, the Netherlands and Denmark; low-risk areas). Polymerase chain reaction (PCR) of a subregion of EBV BamHIC encoding the EBERs demonstrated that 31.8% of the tumours contained the viral genome. No significant differences were observed among the geographical areas. However, positive samples showed higher loads of the EBV genome in the NPC high- and intermediate-risk areas than in the low-risk areas. EBV type 1 was the dominant strain. In situ hybridization studies using a35S-labelled riboprobe for EBER1 and a laser capture microdissection, combined with quantitative PCR, showed that EBV localization was restricted to some tumour epithelial cell clusters. EBV could not be detected in the stroma. Considering the whole population covered, the presence of the EBV genome was not correlated with age, menopausal status, tumour, size, nodal status or histological grade. © 2001 Cancer Research Campaign http://www. bjcancer.com

Hodgkin's disease is now curable in more than 50% of cases, due to its chemo- and radio-sensitivity. However, treatment exposes to a risk of secondary cancer varying from 1 to 10% depending on chemoradiotherapy doses and schedules. We report a case of secondary breast cancer associated with a secondary thyroid cancer observed in a 24-year-old man treated when he was 13 years old by vinblastin and radiation for stage IIA, a Hodgkin's disease.

Kaposi’s sarcoma (KS) is a rare tumor but its incidence is higher following renal transplantation and especially among people of Arab, Jewish and Mediterranean ancestry. We report 3 cases among 120 recipients of renal transplants followed-up for at least 3 years.

The aim of this retrospective study is to detennine prognostic factors for response to CT and survival, in patients (pts) treated with neoadjuvant CT and radiotherapy (RT) for locoregionally advanced non-metastatic NPC. From February 1988 to December 1992, 100 untreated pts received 3 courses of CT regimen with Cisplatin 100 mg/m2 Day l and Adriamycin 30 to 50 mg/m2 Day l for group I (36 pts), 50 to 75 mg/m2 for group II (39 pts) and 75 to 90 mg/m2 for group III (25 pts), repeated every 3 weeks, followed by locoregional RT. Response was assessed after 1 cycle of CT, before and after RT, by the measurement of node areas. Pts characteristics: 70% were men, median age 36.6 years (11 – 66 yrs); T1T2 = 26 pts, T3 = 25, T4 = 49, N2 = 39, N3 = 61; histology; UCNT = 64, non-UCNT = 36. All characteristics were well balanced in the 3 groups. The mean response rate after I cycle was 54.9%, after 3 cycles 78.8%. After RT, we observed 83% of CR, 14% PR and 3% of failure. Twenty seven pts relapsed. With a mean follow up of 27 month, the 3-yrs overall survival (OS) was 73.5% and disease free survival (DFS) 64.2%. Age, sex, node area, histology, T, N, Adriamycin dose-intensity, clinical response to CT, duration of RT and delay between CT and RT were variables studied in univariate and multivariate analysis (Cow model). In univariate study, the factors influencing significatively as and DFS were response after 3 cycles of CT (P Conclusion High dose Adriamycin regimen seems to improve the response rate to CT, which is correlated to as and DFS. Further studies with dose escalation of Adriamycin and growth factors should be done to increase the survival of the bad prognostic pts.

Although GTD is uncommon, it is extremely important because of the high degree of curability with adapted treatment. It is becoming important to preserve young patients (pts) fertility. We reviewed the productive history ofall pts who received chemotherapy (CT) for a GTD at ISA, between January 1982 and December 1993. Only 34 pts had subsequent pregnancies: 19 had molar pregnancies (MP) and 15 choriocarcinomas (CC). The mean age was 27 years (range 17–38). Pts with CC received a combined regimen of CT with Vincristin and Methotrexate 9 pts and Etoposide and Actinomycin 6 pts. All those with MP were treated by a CT associating (Methotrexate and Vincristin). All of them entered a complete remission, 7 after a salvage CT. MP n = 15 CC n = 19 Number of pregnancies 28 29 Normal term pregnancies 18 23 Spontaneous abortion 3 1 Ectopic pregnancy 0 1 Placenta Acreta 0 0 Premature birth 1 1 Congenital malformations 3 3 Conclusion It is actually important to achieve 2 objectives in treating pts with GTD: first to cure them, second to preserve their fertility.

Between 1981 and 1985, the authors studied 21 Tunisian patients with alpha chain disease. Twenty of 21 underwent laparotomy. According to Galian et al. six patients were classified Stage A, two Stage B, and 13 Stage C. The therapeutic regimen included the following: (1) Antibiotics: In the case of intestinal bacterial overgrowth (IBO), antibiotics selected by their antibiograms were delivered; in absence of IBO, metronidazole plus ampicillin were first given. The antibiotic treatment was changed in case of therapeutic failure. (2) Chemotherapy: From 1981 to 1983 a cyclophosphamide, Adriamycin (doxorubicin), teniposide (VM-26), prednisone (CHVP) protocol (Adriamycin 35 mg/m2, teniposide 50 mg/m2 day 2, cyclophosphamide 300 mg/m2 days 2 through 4, prednisone 40 mg/m2 days 1 through 10) was used. After 1983 bleomycin 15 mg, Adriamycin 30 mg, vinblastine 10 mg were given on day 15. Serum immunoelectrophoresis and immunohistochemical study of duodenojejunal specimens were made on a 3-month and 6-month basis, respectively. Survival curve analysis was made according to Kaplan and Meier. Results were as follows: (1) Stage A: Six patients were first treated by antibiotics alone; two complete responses (CR) persisting 42 and 55 months later were observed, respectively. The four antibiotic failures were submitted to further chemotherapy with four subsequent failures and two deaths. (2) Stage B-C: Chemotherapy led to nine CR with one precocious relapse, a salvage chemotherapy allowing to one more CR. (3) All stages mixed, percentage of survival reached 90 +/- 12% at 2 years and 67 +/- 25% at 3 years, all patients alive beyond 3.5 years being disease-free.