Association between Toll-like receptor 2 rs4696483 and rs1898830 polymorphisms and the risk of triple-negative breast cancer.

PURPOSE: Breast cancer (BC) is heterogeneous in clinical manifestation, of which the triple-negative (TNBC) subtype is the most aggressive. This study examines the associations between Toll-Like Receptor (TLR)-2 polymorphisms and the susceptibility to BC and TNBC. METHODS: Genotyping of TLR-2 rs1898830 and rs4696483 polymorphisms was done by real-time PCR in 488 women with BC (130 TNBC, 358 non-TNBC) and 476 cancer-free control women. RESULTS: The minor allele frequency (MAF) of rs4696483 was significantly lower in BC cases compared to controls, and significantly lower frequencies of rs4696483 C/T and higher frequencies of rs1898830 G/G genotypes were seen in BC cases. Significantly higher MAF of rs4696483 and higher C/T and T/T rs4696483 genotypes frequencies were seen in TNBC than in non-TNBC cases. Considering the prevalent AC haplotype as a reference, 2-locus TLR-2 haplotype analysis did not identify any 2-locus TLR-2 haplotype associated with an altered risk of BC or TNBC. Positive associations of rs1898830 and rs4966483 were seen with the histological type in TNBC and negatively with distant metastasis and HR status in TNBC and non-TNBC rs1898830 carriers. In addition, rs4696483 was positively correlated with hormonotherapy and surgery in non-TNBC cases, while rs1898830 was negatively associated with hormonotherapy. Furthermore, rs1898830 was negatively and positively correlated with BMI in TNBC and TNBC cases, respectively, but positively with Ki-67 status. CONCLUSIONS: Our study highlights the association between TLR-2 genetic polymorphisms and BC and TNBC susceptibility, suggesting these variants' diagnostic/prognostic capacity in BC patients and patient subgroups.

Developing learning objectives in postgraduate medical education for family medicine (Tunisia).

Introduction-Aim: The third cycle of medical studies (TCMS) lasts 3 years for the specialty of family medicine (FM) in Tunisia. The members of the FM committee of the Faculty of Medicine of Monastir (FMM) aimed to detail the learning objectives (LO) of residents in FM. METHOD: We used the Delphi method in 2 rounds including a group of experts called FM Learning Objectives Writing Group (FMLOWG) at the FMM. The FMLOWG included 74 university hospital physicians and FM internship supervisors. These members actively participated in the 10 meetings held during the month of March 2022. Three points were discussed: the identification of LOs; the development of training titles and the proposal of the teaching methods to be adopted. The writing was subdivided into 5 domains of LO: transversal, public health, typical population and by system. RESULTS: We identified 1359 LOs for FM residency, for which 552 were LOs per system (40.5%). The learning included 618 training session titles. Residents will have an academic training day every 3 weeks during 9 months for each TCMS year. CONCLUSION: A detailed, MF-specific consensus has been developed by majority of medical specialties. It will be a learning base for learners, a reference for supervisors and TCMS teachers.

[Pain management in cancer patients in a Tunisian hospital]. / La gestion de la douleur chez les patients atteints du cancer dans un hôpital tunisien.

Pain is a common symptom in cancer patients. It is subjective and difficult to communicate. It continues to be outsourced and often overlooked despite the existence of multiple recommendations. The objective of this study is to describe pain management in cancer patients in a Tunisian hospital. This is a prospective study, conducted over one month at the maternity centre of Monastir by an intern in pharmacy using a questionnaire. Of 128 patients assessed, 50 were algic. Twenty-six percent of algic patients were not treated. The neuropathic component of pain was present in 30 % of cases but under treatment. Relief opioids were prescribed in 43 % of cases to relieve pain. Paracetamol was prescribed in 26 % of cases. Ten percent of patients use paracetamol self-medication. Sixteen percent of patients have tried non-pharmacological means, of which 62 % consume plants. To optimise the management of pain at our centre, the available analgesic sheets have been developed, validated by the medical staff and disseminated in the departments of carcinology and oncohematology. Therapeutic education sessions were also scheduled to warn patients about the risks of self-medication and misuse of medicinal plants. Pain management is complex. It requires respect for international recommendations, but especially for the efforts made by all stakeholders.

Association between HER2 and IL-6 genes polymorphisms and clinicopathological characteristics of breast cancer: significant role of genetic variability in specific breast cancer subtype.

Clinical implications of single nucleotide polymorphisms (SNPs) in breast cancer have been explored to determine the impact of SNP in modulating the pathogenesis of breast cancer. This study aimed to evaluate the association between HER2 (rs2517956) and (IL-6) (rs1800795 and rs2069837) and clinicopathological characteristics in HER2-positive and HER2-negative breast cancer in Tunisian women. A retrospective cohort study included 273 patients. Genomic DNA was extracted from peripheral blood samples, and genotyping of selected SNP was performed by PCR-RFLP assays. Statistical analysis was then carried out to assess genotypic frequencies and genetic association in relation to breast cancer subtypes. SHEsis software was applied to IL-6 haplotypic structure analysis. The distribution of genotype frequencies of rs2517956, rs1800795 and rs2069837 showed no statistically difference between HER2-positive and HER2-negative breast cancer. HER2 (rs2517956) was associated with tumor size (p = 0.01) and age at diagnosis (p = 0.02) in HER2-negative breast cancers, but no significant association was observed in HER2-positive breast cancer. For IL-6 gene, none of the clinicopathological parameters were associated with rs1800795 and rs2069837 in both breast cancer subtypes (p > 0.05). SHEsis analysis revealed a high linkage disequilibrium between rs1800795 and rs2069837; differences in the distribution of IL-6 two loci haplotypes were statistically negative between HER2-positive and HER2-negative breast cancer (p = 0.20) which confirmed no association with HER2 overexpression. This study demonstrates that rs2517956 is associated with clinicopathological characteristics in HER2-negative breast cancer, which could have a differential prognostic role compared to HER2-positive breast cancer.

Progesterone Receptor (PGR) Gene Variants Associated with Breast Cancer and Associated Features: a Case-Control Study.

Insofar as altered estrogen receptor-progesterone receptor (PR) expression contribute to breast cancer pathogenesis, previous studies examined the association of genetic variation in PR gene (PGR) with breast cancer, but with mixed outcome. We evaluated the association between PGR variants, and breast cancer and associated features. A retrospective case-control study involving 183 female breast cancer patients, and 222 control women. PGR genotyping was done by real-time PCR. Minor allele frequencies of rs1042838, rs590688, and rs10895068 PGR gene polymorphisms were significantly higher in breast cancer patients compared to controls. Patients carrying rs1042838 G/T, rs590688 C/C, and rs10895068 G/A genotypes had higher risk of breast cancer, while carriage of rs3740753 G/G genotype was associated with marginal reduction in breast cancer risk. In addition, carriage of rs1042839, rs3740753, and rs10895068 minor allele was associated with Her2 status, while rs3740753 and rs10895068 were associated with effective hormone replacement therapy. Furthermore, carriage of rs10895068 minor allele in breast cancer women were also associated with age at first pregnancy, hormone receptor (RH) status, and previous use of oral contraceptives. PGR haploview analysis documented moderate-strong linkage disequilibrium (non-random association of alleles at different loci) between 7 of the 8 tested PGR SNPs, thus allowing construction of 7-locus PGR haplotypes. Two haplotypes, ATGCCGA and GTGCCGA, both containing rs590688, were positively associated with breast cancer, thus assigning a breast cancer-susceptible nature to these haplotypes. PGR rs1042838, rs590688, and rs10895068, and ATGCCGA and GTGCCGA haplotypes are related with increased breast cancer susceptibility in Tunisian women.

Common matrix metalloproteinase-2 gene variants and altered susceptibility to breast cancer and associated features in Tunisian women.

A role for matrix metalloproteinase polymorphisms in breast cancer development and progression was proposed, but with inconclusive results. We assessed the relation of matrix metalloproteinase-2 variants with breast cancer and related phenotypes in Tunisians. This case-control retrospective study involved 430 women with breast cancer and 498 healthy controls. Genotyping of matrix metalloproteinase-2 rs243866, rs243865, rs243864, and rs2285053 was analyzed by allelic exclusion. The minor allele frequency of rs2285053 was significantly lower in women with breast cancer cases as compared to control women; minor allele frequencies of the remaining single-nucleotide polymorphisms were similar between cases and control women. The distribution of rs243865 and rs2285053 genotypes was significantly different between breast cancer patients and control subjects. This persisted when key covariates were controlled for. None of the matrix metalloproteinase-2 variants were associated with estrogen receptor positivity, progesterone receptor positivity, or with double estrogen receptor-progesterone receptor positivity in breast cancer patients. Matrix metalloproteinase-2 rs243866, rs243865, and rs243864 were positively associated with menstrual irregularity and histological type, while rs243866 and rs2285053 were negatively associated with menarche and nodal status. In addition, rs2285053 was negatively associated with triple negativity, tumor size, distance metastasis, molecular type, and chemotherapy. Haploview analysis revealed high linkage disequilibrium between matrix metalloproteinase-2 variants. Four-locus Haploview analysis identified haplotypes GCTT and GTTC to be negatively associated with breast cancer, which remained statistically after controlling for key covariates. Matrix metalloproteinase-2 alleles and genotypes, along with four-locus haplotypes, are related to reduced susceptibility to breast cancer in Tunisian women, suggesting a protective effect.

Association of Genetic Variants in NF-kB with Susceptibility to Breast Cancer: a Case Control Study.

Insofar as altered NF-κB signaling stemming from the presence of specific genetic variants in NF-κB gene contribute to cancer pathogenesis, this study evaluated the association between NF-κB rs147574894/I552V, rs148626207/M860T rs3774937 and rs1598859 variants and breast cancer and associated features and complications. This was a retrospective case-control study, which involved 207 women with breast cancer, and 214 cancer-free women who served as controls. NF-κB genotyping was done by real-time PCR. Significantly higher rs3774937 minor allele frequencies (MAF), and lower rs147574894 MAF were seen among breast cancer patients, thereby imparting disease susceptibility and protective nature to these variants, respectively. Significant association of rs3774937 and rs147574894 genotypes with breast cancer was seen under the dominant model. Histological type and grade, molecular type, Her2 positivity and ER+/Her2- correlated positively, while distant metastasis negatively correlated with rs3774937. On the other hand, rs147574894 negatively correlated with histological type and grade, tumor size, Her2 positivity, molecular type, and ER+/Her2-, while rs148626207 correlated positively with histological grade, but negatively with distant metastasis and triple-negative status. Breast cancer-susceptible and -protective 4-locus haplotypes were also identified. This is the first report that addresses the contribution of NF-κB variants to the pathogenesis of breast cancer in Middle Eastern-North African population, and the first to document positive association of rs3774937 with breast cancer.

[Genital metastases from breast cancer: study of 3 cases and literature review]. / Métastases génitales du cancer du sein: étude de 3 cas et revue de la littérature.

Breast cancer is the most common cancer among women. Prognosis depends, in large part, on the presence of metastases. Liver, skeleton and lungs are the most frequent metastatic sites, whereas genital metastases are more rare and less known. The detection of an ovarian mass in a woman with a history of breast cancer raises the question of its primary or secondary origin. The frequency of ovarian metastases reported in the literature is approximately 20-30%. However, when an ovarian mass is detected in a woman with breast cancer, primary ovarian tumor is diagnosed three times more often than a metastasis. Cervical, uterine or corporeal metastases are even more rare. They are often diagnosed late, due to their clinical latency; transvaginal ultrasound coupled with Color Doppler and Pap smear must be performed as first-line examinations knowing that their screening performance in patients with ovarian masses is deemed low. An increase in CA 15-3 and CEA tumor markers must lead clinicians to investigate for metastases, but it doesn't provide diagnostic orientation toward a specific metastatic site. Finally, only anatomo-athological examination allows certain diagnosis. We here report 3 cases of genital metastases from primary breast cancer (two patients with ovarian metastases and one patient with cervico-uterine metastasis) in order to highlight the role of accurate and regular genital examination in the monitoring of patients with breast cancer and to discuss the predictive factors for their occurrence.

Adenosquamous carcinoma of the right colon: A case report and review of the literature.

INTRODUCTION: Adenosquamous carcinoma is a rare colorectal tumor with both an adenocarcinoma and a squamous cell carcinoma component. To the best of our knowledge, only few cases have been reported in the literature. CASE PRESENTATION: We report a case of a 46-year-old woman, hospitalized for large bowel obstruction syndrome. Computed tomography scan showed an irregular mass of the right colic angle, responsible for an occlusive syndrome with distension of the right colon, the appendix and the terminal ileum. The patient underwent right hemicolectomy with D2 lymphadenectomy. Histopathological examination revealed mixed adenocarcinoma and squamous carcinoma. Adjuvant chemotherapy was prescribed for the patient. DISCUSSION: Adenosquamous carcinoma is a rare colorectal neoplasm revealed by non-specific complaints. Its clinicopathology is not yet understood. Preoperative diagnosis is often difficult. Surgical resection remains the mainstay of treatment. CONCLUSION: Adenosquamous carcinoma is a malignant tumor with poorer prognosis than adenocacinomas.

Factors Predictive of Quality of Life among Breast Cancer Patients

Background: Due to progress in medical care, the number of survivors from cancer has increased significantly during recent years and this raises the question of the quality of life (QoL), especially of the many women treated for a breast cancer. This paper focuses on correlations of QoL with anxiety and depression on the one hand and with socio demographic, anatomo-clinical and therapeutic parameters on the other. Methods: In this cross-sectional study, seventy patients were enrolled and filled in two auto-questionnaires, both in validated Arabic versions: The SF-36 for assessment of QoL and the Hospital Anxiety and Depression Scale (HAD-S) for evaluation of anxiety and depression. The statistical approaches used to determine predictive factors were bivariate correlations to determine relationships between quantitative variables, and T-tests and one-way Anova to analyze links between qualitative and quantitative variables. Results: The QoL of patients was altered with an SF-36 mean total score of 54.0 ± 22.7, and the alteration affects the different aspects. The mean scores for anxiety and depression in patients were 6.91 ± 4.72 and 6.24 ± 3.88, respectively. The results of this study suggested an association between the QoL and chemotherapy (p= 0.014) and its adverse effects (p=0.01), as well as anxiety (p= 0.0001) and depressive symptoms (p= 0.0001). Socio-demographic factors, the stage of the cancer, and surgery, radiotherapy or hormone therapy did not appear to have significant effects. Conclusion: The management of breast cancer patients needs a collaborative approach between oncologists, gynecologists, psychologist and psychiatrists.

Differential association of ESR1 and ESR2 gene variants with the risk of breast cancer and associated features: A case-control study.

BACKGROUND: Estrogen is key to breast cancer pathogenesis, and acts by binding its receptor (ER), which exists as ERα and ERß, encoded by ESR1 and ESR2 genes, respectively. Studies that investigated the association of ESR1 and ESR2 variants with breast cancer yielded mixed outcome, and ethnic contribution was proposed. We evaluated the association between ESR1 and ESR2 variants and breast cancer and associated features in Tunisian women. METHODS: Retrospective case-control study involving 207 female breast cancer patients, and 284 control women. Genotyping was done by real-time PCR. RESULTS: Minor allele frequencies (MAF) of tagging SNPs rs2234693 and rs3798577 (ESR1) were significantly higher, while MAF of rs1256049 (ESR2) was significantly lower in breast cancer patients vs. CONTROLS: Patients carrying rs3798577 genotypes had higher risk, while rs1256049 genotype carriers had reduced risk of breast cancer. The association of ESR1 and ESR2 gene variants with breast cancer depended on ER and Her-2 status. ESR1 rs3798577 and ESR2 rs1256049 were associated with breast cancer in ER-positive cases, and ESR1 rs2234693, and rs3798577 were associated with breast cancer in Her-2-negative cases, while the association of ESR2 rs1256049 with breast cancer was seen in Her-2 positive cases. Haploview analysis identified 4-locus ESR1 haplotypes that were positively (CGTT, TACC, and TACT), and negatively (CGTC) associated with breast cancer. No ESR2 haplotypes associated with breast cancer were identified. CONCLUSION: ESR1 alleles and genotypes, and specific 3-locus ESR1 haplotypes are related with increased breast cancer susceptibility in Tunisian women. However, ESR2 variant and specific 1-locus ESR1 haplotype have a protective effect.

Breast diseases in women over the age of 65 in Monastir, Tunisia.

As life expectancy is on the rise, it is predicted that a growing number of people will live beyond the age of 65 and therefore a higher number of elderly women will have breast diseases requiring significant health care and services. This study is aimed at investigating the characteristics, the treatment and outcomes of women older than 65 years old treated for breast diseases at our institution. This was a retrospective study covering the period from January 2003 to December 2011. It involved 92 patients aged over 65 and treated for breast disease in the Maternity Center of Monastir, Tunisia. The data included characteristics of patients and tumors, treatment and outcomes that were obtained through data extraction sheets. We reported a study of 92 women over the age of 65 of whom 77 women had malignant breast disease (83.6%) and 15 benign breast diseases (16.4%). Breast cancer was discovered at a mean age of 72.5 ± 6.6 years. Distant metastases were found in 5.3% of cases and infiltrative ductal carcinoma was detected in 85.7% of patients. Hormonal receptors were positive for estrogens in 64.7% of cases. Surgical treatment was performed in 73 patients and adjuvant treatment was prescribed for 67 women (86%). The complication rate was 16.6% among the 73 patients who underwent surgery. Benign breast diseases represented 16.3% of the mammary pathologies. Abscesses and fibrocystic mastopathy were the most frequent histological diagnoses. Despite great interest in geriatric gynecological pathology worldwide, many questions related to how optimally treat this patient population remain unanswered. In this study, a surgical treatment was performed in 94.8% of breast cancer patients and the complication rate was 16.6%.

[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.