Physical activity and quality of life among breast cancer survivors.

INTRODUCTION AND AIM: To assess physical activity (PA) and its determinants in breast cancer survivors (BCS), attending a Tunisian hospital, as well as to assess their quality of life (QOL) and examine the relationship between PA and BCS'QOL. METHODS: We conducted a cross-sectional study among BCS attending the outpatient oncology, gynecology and radiotherapy clinics at a Tunisian hospital in April 2022 using a self-administered questionnaire. The valid Arabic version of the International Physical Activity. Questionnaire short version was used to assess PA and sitting time. QOL was assessed using the valid Arabic version of the 12-item Short-Form health survey. RESULTS: A total of 95 BCS were recruited. BCS reported overall moderate PA levels with a median MET of 1440 (IQR 680- 2400) minutes/week and a mean total sitting time of 281.79±134.36 minutes/day. Overall, patients aged 50 years and above had significantly lower levels of sitting time (231.43±129.32vs 332.14±121.63, p= 0.04). Similarly, subjects aged 50 years and above, and of rural origin had higher levels of PA (1908.5 (IQR 939.7-3268.5) vs. 1266 (IQR 471-2946), p= 0.114 and 1788.5 (IQR 1072.5-3252) vs. 1440 (IQR 537-3057), p= 0.259 respectively). Regarding BCS'QOL, they showed moderate disability in the physical component (39.3 ±7.08) , and mild disability in the mental component (43.94 ±9.23). BCS' QOL was significantly correlated to PA (r=0,258, p=0,012). CONCLUSION: Adherence to regular PA is effective in improving BC patients' survival rate. Therefore, to enhance survivors' QOL, a healthy lifestyle including regular PA is well recommended.

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.

Transcutaneous canine breast cancer detection in Tunisia: a pilot study.

BACKGROUND: Breast cancer in Tunisia is often diagnosed at a late stage with long delay in time to consultation and to diagnosis.The aim of this study is to estimate the sensitivity and specificity of the transcutaneous breast cancer detection by canine olfactionin Tunisian women and to identify the potential confounding factors. METHODS: This is a diagnostic case control study that took place from October 2021 to November 2022 in the Department of Medical Oncology at the University Hospital Farhat Hached of Sousse and in the security and training dog center located in Sousse (K9 Dog Center Security & Training). A two-year-old male Belgian Malinois was trained to detect breast cancer on skin secretion samples in compresses that had been worn overnight by women on their breast and then a double-blind testing was performed. There was no contact between women and the dog. From the mentioned responses of the dog, four parameters were calculated: sensitivity, specificity, Positive Predictive Value (PPV) and Negative Predictive Value (NPV). RESULTS: Two hundred women were included in this trial: 100 breast cancer (BC) patients recruited from Farhat Hached University Hospital of Sousse and 100 healthy volunteers (HV).The calculated sensitivity was 84% (95% CI 78-89%) and the calculated specificity was 81% (95% CI 75-86%). The calculated predictive values were: PPV = 83,51% (95% CI 78,37-88,65%) and NPV = 81,55% (95% CI 76.17-86.93%). In the multivariate study, only four confounding factors of test's sensitivity were retained: age (OR = 1.210 [95% CI = 1.085-1.349]; p = 0.001), history of diabetes(OR = 0.017 [95% CI = 0.001-0.228]; p = 0.002), sampling at hospital (OR = 0.010 [95% CI = 0.003-0.464]; p = 0.010) and testing during chemotherapy courses (OR = 0.034 [95% CI = 0.003-0.404]; p = 0.007).For test's specificity, we retained the three following confounding factors: age (OR = 1,104 [95% CI = 1.021-1.195]; p = 0.014), history of benign mastopathy (OR = 0.243 [95% CI = 0.074-0.805]; p = 0.021)and history of arterial hypertension (OR = 0.194 [95% CI = 0.053-0.707]; p = 0.013). CONCLUSION: This is a pilot study that opens new avenues in developing a reliable cancer diagnostic tool that integrates the dog's olfactory ability to detect breast cancer using a transcutaneous sampling method. It could be a pre-test to select patients who are eligible to a screening mammogram, especially in low-income countries where there is no national mammography screening program. PACTR. ORG IDENTIFIER: PACTR202201864472288, registration date 11/01/2022.

Complementary and alternative medicine in oncology: knowledge, attitude and practice among Tunisian healthcare workers.

PURPOSE: Over the past years, there has been a considerable increase in complementary and alternative medicine (CAM) use among cancer patients. However, guidance from health care workers (HCWs) is not always provided. We aimed to determine the knowledge, attitude and practice of Tunisian HCWs regarding the use of CAM in cancer patients. METHODS: We conducted a multicenter cross-sectional study over 5 months from February to June 2022 among HCWs caring for cancer patients in the Tunisian center region. Data were collected using a self-administered questionnaire developed by our investigators. RESULTS: The level of knowledge about CAM was declared limited by 78.4% of our population. The best known CAM therapies were herbal medicine and homeopathy while chiropractic and hypnosis where the least. HCWs who had sought information on CAM represented 54.3% of our sample and the main source of information was the Internet (37.1%). A positive attitude towards the use of CAM was found in 56% of HCWs. The integration of CAM into supportive care in oncology was approved by 78% of HCWs. Concerning training on CAM, 78% declared its necessity for HCWs and 73.3% expressed a desire to have it. A personal use of CAM was found in 53% of HCWs while 38.8% had previously used CAM in the treatment of their cancer patients. CONCLUSION: The majority of HCWs had a positive attitude towards the use of CAM in oncology despite their poor knowledge about it. Our study emphasizes the need to train HCWs dealing with cancer patients on CAM.

Quality of life in Tunisian colorectal cancer patients: a cross-sectional study.

PURPOSE: Quality of life (QOL) of colorectal cancer (CRC) patients has been little studied in Tunisia. The aim of this work was to evaluate the QOL of CRC patients and to identify factors that may influence it. METHODS: A cross-sectional, study spread was made over a period of 6 months on patients with CRC treated in the department of Medical Oncology of Farhat Hached University Hospital of Sousse. The EORTC questionnaires translated and validated in Arabic (QLQ-C30 and QLQ-CR29) were used. RESULTS: 142 patients diagnosed with colon or rectal cancer were enrolled. The overall QOL score was 58.5 ± 29.1. The emotional and sexual functional dimensions were the most affected, especially in women and patients under 50 years of age. QOL scores were higher in patients who were in complete remission (71.4 ± 24.7) and in good general condition (63.7 ± 26.6) physical activity may have a significant influence on all functional dimensions of QOL (p < 0.001). Fatigue was significantly (p < 0.001) more present when there was a sedentary lifestyleradiotherapy, palliative chemotherapy (1st and 2nd line) and targeted therapy. CONCLUSION: Evaluating quality of life of patients with colorectal cancer in Tunisia is necessary especially those under 50 years old and in women. Laparoscopic surgery with restoration of intestinal continuity, less toxic palliative chemotherapy protocols, more accessibility to new radiotherapy technics will improve QOL of CRC patients. Physical activity and nutrition support are also essential in promoting QOL of these patients.

Assessment of depression, anxiety and fatigue in Tunisian patients in recovery from colon cancer and their impact on quality of life.

PURPOSE: Colon cancer survivors can experience several post-treatment consequences that include fatigue and often report severe psychological illnesses such as depression or anxiety. There is little published quantitative data on the quality of life and psychological well-being associated with the health of Tunisian colon cancer survivors. METHODS: A total of 60 recovering colon cancer patients underwent a structured interview, which included the Hospital Anxiety and Depression (HADS) scale, the Piper fatigue scale and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). RESULTS: Patients were 59.26 years old on average. The median length of remission was 33.3 months. Surgery was performed on all patients, followed by 96.7% adjuvant chemotherapy. 15.1% of study participants were in the severe category for the depression score and 10% were in this category for the anxiety score. Ninety-one percent reported pathological fatigue scores on the Piper scale. However, only 8.33% were experiencing severe fatigue. According to the QLQ-C30 assessment, the overall quality of life was slightly impaired with an overall average score of 79.54 ± 16.98. Anxiety, depression and fatigue negatively affect global health outcomes and all their dimensions. CONCLUSION: Even in the recovery phase, colon cancer patients can see their quality of life deteriorate. It comes out of their psychological experience and their physical life. It is, therefore, crucial to provide greater attention to these patients for holistic and multi-disciplinary care.

DPYD and TYMS polymorphisms as predictors of 5 fluorouracil toxicity in colorectal cancer patients.

Colorectal cancer (CRC) is the third most common cancer and the fourth leading cause of cancer death. 5-Fluorouracil (5-FU) is an essential component of systemic chemotherapy for CRC. Our objective was to determine the genotypic frequency of polymorphisms affecting dihydropyrimidine dehydrogenase (DPYD) and thymidylate synthetase (TYMS) genes and to correlate the genetic profile with the toxicity due to 5-FU, also considering nongenetic factors. This is a prospective study that involved 66 patients. We extracted DNA by salting out methods. We carried out the genotyping of the different polymorphisms by simple PCR for the TYMS 5'UTR and by PCR-RFLP for DPYD: 1905 + 1 G > A, 85 T > C, 496 A > G, 1679 T > G, c.483 + 18G > A and the TYMS: 5'UTR VNTR, 5'UTR G > C and 3'UTR. The study of the association of DPYD and TYMS polymorphisms with the various signs of toxicity under 5-FU revealed that the polymorphisms 496 A > G were significantly associated with hepatotoxicity: OR = 3.85 (p = 0.04). In addition, 85 T > C was significantly associated with mucositis and neurotoxicity: OR = 4.35 (p = 0.03), OR = 3.79 (p = 0.02). For TYMS, the only significant association we observed for 5'UTR with vomiting: OR = 3.34 (p = 0.04). The incidence of adverse reactions related to 5-FU appears to be influenced in patients with CRC by the identified DPYD and TYMS gene polymorphisms in the Tunisian population.

Functional characterization of MLH1 missense variants unveils mechanisms of pathogenicity and clarifies role in cancer.

Lynch syndrome is a heritable condition caused by a heterozygous germline inactivating mutation of the DNA mismatch repair (MMR) genes, most commonly the MLH1 gene. However, one third of the identified alterations are missense variants, for which the clinical significance is unclear in many cases. We have identified three MLH1 missense alterations (p.(Glu736Lys), p.(Pro640Thr) and p.(Leu73Pro)) in six individuals from large Tunisian families. For none of these alterations, a classification of pathogenicity was available, consequently diagnosis, predictive testing and targeted surveillance in affected families was impossible. We therefore performed functional laboratory testing using a system testing stability as well as catalytic activity that includes clinically validated reference variants. Both p.(Leu73Pro) and p.(Pro640Thr) were found to be non-functional due to severe defects in protein stability and catalytic activity. In contrast, p.(Glu736Lys) was comparable to the wildtype protein and therefore considered a neutral substitution. Analysis of residue conservation and of the structural roles of the substituted residues corroborated these findings. In conjunction with the available clinical data, two variants fulfil classification criteria for class 4 "likely pathogenic". The findings of this work clarify the mechanism of pathogenicity of two unclear MLH1 variants and enables predictive testing and targeted surveillance in members of carrier families worldwide.

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.

Adenocarcinoma of intestinal type arising in mature cystic teratoma of ovary: A diagnostic dilemma.

Adenocarcinomas of intestinal type arising in mature cystic teratoma of ovary (MCT) are extremely rare and remain a diagnostic dilemma because of its similarities with MCT. Serum tumor markers CEA and SCC and also MRI may help in the preoperative diagnosis. Pathologist experience helps in intraoperative diagnosis.

Targeted next generation sequencing screening of Lynch syndrome in Tunisian population.

A high colorectal cancer (CRC) incidence is observed in Tunisia, with a relatively high proportion of patients developing CRC before the age of 40. While this suggests a genetic susceptibility, only a few Tunisian Lynch Syndrome families have been described. In this study we aimed to identify the underlying genetic cause in 32 patients with early onset CRC and/or a positive family history. Of twenty-four patients' tumor or biopsies could be analyzed with immunohistochemical staining to detect loss of expression of one of the MMR proteins. Ten tumors showed loss of expression, of which one tumor was from a patient where a germline pathogenic MSH2 variant was detected previously with Sanger sequencing. Next generation sequencing of the MMR, POLE and POLD1 genes was performed in leukocyte and tumor DNA of the remaining nine patients, as well as in two patients with MMR-proficient tumors, but with severe family history. In six of 11 patients a germline variant was detected in MLH1 (n = 5) or MSH2 (n = 1). Two of six patients were from the same family and both were found to carry a novel in-frame MLH1 deletion, predicted to affect MLH1 function. All MLH1 variant carriers had loss of heterozygosity with retention of the variant in the tumors, while a somatic pathogenic variant was detected in the patient with the germline MSH2 variant.

Molecular Diagnostic and Prognostic Subtyping of Gliomas in Tunisian Population.

It has become increasingly evident that morphologically similar gliomas may have distinct clinical phenotypes arising from diverse genetic signatures. To date, glial tumours from the Tunisian population have not been investigated. To address this, we correlated the clinico-pathology with molecular data of 110 gliomas by a combination of HM450K array, MLPA and TMA-IHC. PTEN loss and EGFR amplification were distributed in different glioma histological groups. However, 1p19q co-deletion and KIAA1549:BRAF fusion were, respectively, restricted to Oligodendroglioma and Pilocytic Astrocytoma. CDKN2A loss and EGFR overexpression were more common within high-grade gliomas. Furthermore, survival statistical correlations led us to identify Glioblastoma (GB) prognosis subtypes. In fact, significant lower overall survival (OS) was detected within GB that overexpressed EGFR and Cox2. In addition, IDH1R132H mutation seemed to provide a markedly survival advantage. Interestingly, the association of IDHR132H mutation and EGFR normal status, as well as the association of differentiation markers, defined GB subtypes with good prognosis. By contrast, poor survival GB subtypes were defined by the combination of PTEN loss with PDGFRa expression and/or EGFR amplification. Additionally, GB presenting p53-negative staining associated with CDKN2A loss or p21 positivity represented a subtype with short survival. Thus, distinct molecular subtypes with individualised prognosis were identified. Interestingly, we found a unique histone mutation in a poor survival young adult GB case. This tumour exceptionally associated the H3F3A G34R mutation and MYCN amplification as well as 1p36 loss and 10q loss. Furthermore, by exhibiting a remarkable methylation profile, it emphasised the oncogenic power of G34R mutation connecting gliomagenesis and chromatin regulation.

Tunisian adult's Hodgkin lymphoma Study Group.

The Tunisian adult's Hodgkin lymphoma (HL) Study Group was created in 1999. It aimed to improve the management of this curable hematologic malignancy by standardizing the diagnosis, assessment of disease, treatment management and therapeutic evaluation in different Tunisian centers (Hematology, oncology and radiotherapy).Since 1998, four versions of the prospective national protocol for treating adult Hodgkin lymphoma have succeeded (MDH99, MDH2002, MDH2008, MDH2015). Each version was based on the results of the previous version and analyzed according to new data from the literature. Due to this national study group, the number of patients lost to follow decreased significantly (30% before the creation of the group and only 3% for patients treated with MDH2008), the complete and uncertain response rates have improved (75% before the creation of the group and 92% in patients treated with MDH2008) with dramatically improved rates of overall survival from 57% to 90%. On the other hand there was an improvement of toxic death rate (13% of toxic deaths in MDH2002 to 4.37% in the MDH2008) with a decrease of the respective rate of primary failure and relapse by 17% and 12.5% in MDH2002 against the 11.4% and 7.8% in the MDH2008. This resulted in an improvement in overall survival (90%) and event-free survival at 5 years (75%). Now with the introduction of positron emission tomography in Tunisia, we hope yet to finalize the assessment of response and thus better adapt the treatment of this disease. Our objective remains the improvement of event-free survival rate to reach 80%.

Assessment of MYCN amplification status in Tunisian neuroblastoma: CISH and MLPA combining approach.

BACKGROUND: Neuroblastoma (NB) shows a complex combination of genetic aberrations. Some of them represent poor genetic prognosis factors that require specific and intensive chemotherapy. MYCN amplification consists of the major bad outcome prognostic factor, it is indeed frequently observed in aggressive neuroblastomas. To date different methods are used for MYCN status detection. OBJECTIVES: The primary aim of our study was to provide a critical assessment of MYCN status using 2 molecular techniques CISH and MLPA. We also focused on the correlation between neuroblastoma genetic markers and patient's clinical course among 15 Tunisian patients. METHODS: we developed a descriptive study that includes 15 pediatric Tunisian patients referred to our laboratory from 2004 to 2011. We reported the analysis of fresh and FFPE NB tumors tissues. RESULTS: No significant correlation was found between COG grade and patients overall survival. Assessment of NMYC gene copy number by kappa statistic test revealed high concordance between CISH and MLPA tests (kappa coefficient = 0.02). CONCLUSION: Despite misdiagnosing of MYCN status fewer than 5 copies, MLPA remains an effective molecular technique that enables a large panel of genomic aberrations screening. Thus combining CISH and MLPA is an effective molecular approach adopted in our laboratory. Our results allow pediatric oncologists to set up the first Neuroblastoma therapeutic strategy based on molecular markers in Tunisia.

[The role of general practitioners in the management of cancer patients from the central region of Tunisia: a retrospective study of 215 physicians]. / Quelle place pour les praticiens generalists dans la prise en charge des patients cancéreux de la region du centre Tunisien: Etude retrospective à propos de 215 médecins.

BACKGROUND: General practitioners have a major contribution in cancer prevention and screening. However, their contribution in the treatment plan management and in the post treatment follow-up of cancer patients needs to be clarified. OBJECTIVE: To evaluate the contribution of general practitioners of the public and private sectors in the management of cancer patients during and after the treatment protocol. To analyze the problems they encounter and find the possible solutions. METHOD: A retrospective declarative KAP (Knowledge, Attitudes and Practices) survey was conducted from first September 2010 to 28 February 2011 in the central region of Tunisia among 215 primary care physicians in the public and private sectors. The questionnaire focused on their effective involvement, the role during treatment, follow up and supportive care. RESULTS: Nearly 80% of physicians who participated in the survey were involved in the management of their patients, primarily by ensuring adherence to their treatment (42.9%), in the follow up care after treatment (42.3%) and in palliative care (29%), however the majority has never prescribed opioid drugs (66.5%). Only 46.6% of the physicians announced the diagnosis of cancer to their patients. The questioned doctors deplored the lack of training in oncology (22.8%) and the feeling of being excluded from the management of their patients once they have addressed them to their specialist peers (48.8%). The interviewed physicians expressed their wish to have a further medical training in oncology (79.5%) and to join a structured cancer network (55.8%). CONCLUSION: The majority of interviewed general practitioners of our region were engaged in cancer patients' care. However, gaps were identified especially in palliative care and in prescribing opioid drugs. Promoting continuing education in this field and the establishment of cancer networks will allow extend the scope of general practitioners' intervention in the cancer network.

[Study of sexuality among Tunisian women in remission from non-metastatic breast cancer, about 100 women]. / Étude de la sexualité chez les femmes Tunisiennes en rémission complète d'un cancer du sein non métastatique, à propos de 100 femmes.

The prognosis of breast cancer has significantly improved during the last years due to progress of the treatment options. It is a public health problem because of its frequency, severity, physical and psychological consequences. Quality of life appears increasingly as fundamental criteria in the assessment of treatment outcomes. This underlines the specific impact on sexuality. Aim. To evaluate the frequency and type of sexual dysfunction in 100 patients treated for non-metastatic breast cancer in post-treatment monitoring in external consultation of the Department of Oncological Medicine, CHU Farhat Hached, Sousse. Then, to identify predictive factors of these disorders. Procedure. Sexuality and body image were evaluated respectively using two scales: Relationship and Sexuality (RSS) and Body-Esteem Scale for Adolescents and Adults (BESAA). Results. Sexual desire has been affected by the disease and its treatment for 47 women. The capacity to achieve orgasm was reduced in 61 patients. Twenty felt less sexually attractive. Fifty-three women had reported a decrease in the frequency of sexual intercourse. Sixteen patients had reported a fear of sex. Dyspareunia and vaginal dryness were present in 45 women. The analytic study had found that sexual problems are related to the rural origin, the profession of the husband, the premenopausal period, lack of breast reconstruction, the CMF chemotherapy protocol (cyclophosphamide, methotrexate, 5-fluorouracil) and number of cycles of chemotherapy. Body image was significantly altered in patients with sexual dysfunction. In addition, psychosocial factors that best predicted sexual difficulties are the perception by the wife of an emotional distance in the relationship with her partner and fear of sex. Conclusion. The support for these sexual difficulties requires a joint and collaborative approach between oncologists, gynecologists, psychiatrists and sexologists.

Impact of menstrual and reproductive factors on breast cancer risk in Tunisia: a case-control study.

This report examined the relationship between menstrual and reproductive factors and breast cancer risk. The case-control study was conducted on 400 women with histological confirmed breast cancer operated during the 2006-2009 period at Farhat Hached University Hospital, Sousse, Tunisia, and 400 cancer-free controls, aged 25-75 years. The menstrual and reproductive history was assessed using a structured questionnaire. Odds ratios (ORs), 95 % confidence intervals (CI) and a full confounding assessment, included in this analysis, were derived using logistic regression. A positive family history of breast cancer was associated with a significantly increased risk of breast cancer (OR = 5.15, 95 % CI 1.48-17.94). Significant risk reduction was found with later age at menarche (P = 0.02). There was an insignificant increase in risk with later age at menopause (≥ 51 years; OR = 1.87), later age at first live birth (≥ 26 years; OR = 1.76) and nulliparous women compared to parous women (OR = 2.35). An insignificant decrease in risk was observed with increasing parity number (≥ 3 delivery; OR = 0.86). A significantly reduced risk of breast cancer was found for those women whose lifetime duration of breastfeeding was 73-108 months and for those who breastfed for ≥ 109 months (P = 0.00). Our findings suggest that age at menarche and breastfeeding history have great effects on breast cancer risk among Tunisian women.

Effect of chemotherapy on autoimmune hepatitis in thymoma: a case report and literature review.

Autoimmune hepatitis (AIH) has rarely been described as an autoimmune paraneoplastic syndrome of thymoma. This case is the seventh case of AIH revealed by cholestasis few years after the diagnosis of thymoma and the first case treated with chemotherapy alone. We report in this paper a new approach to this rare severe condition. A 29 year-old man presented with chest pain and dyspnea with a history of thymoma surgically removed 4 years ago. CT scan showed the recurrence of an anterior mediastinal mass. Biology showed elevated liver enzymes and profound cholestasis. No sign of viral or toxic hepatitis or bile duct abnormalities were observed. Autoimmune antibodies, except for the anti-nuclear antibody, were negative. Liver biopsy showed active chronic AIH. The patient was diagnosed with recurrent thymoma with AIH and underwent 6 cycles of chemotherapy. A complete response on thymoma and cholestasis was obtained after 10 months of follow-up. Steroids and immunosuppressors are the standard treatment for AIH. The effect of chemotherapy as a specific treatment of this paraneoplastic syndrome needs to be considered.