Inflammatory breast cancer: As surgical oncologists, what can we do?

Breast cancer surgery is the primary treatment for early-stage breast cancer. However, inflammatory breast cancer (IBC), with its specific presentation characterized by skin invasion, is unfit for primary surgery. According to the different guidelines, the management of IBC is trimodal with the coordination of oncologists, surgeons, and radiation therapists. Advances in breast cancer imaging and the development of more targeted therapies make new challenges for this aggressive cancer. This chapter aims to provide an update on the role of surgery in IBC. Radical surgery is still considered the standard surgical treatment in IBC. Some authors suggest a conservative surgery in patients with a clinical response to chemotherapy without affecting survival. For lymph node surgery, the sentinel lymph node biopsy (SLNB) is not feasible in IBC patients, according to the existing studies. However, prospective studies on SLNB are needed to verify its reliability after chemotherapy for a specific group of patients. In the metastatic IBC, surgery can be considered if there is a good response after chemotherapy or for uncontrolled symptoms. Existing studies showed that surgery may impact survival for these patients. Prospective studies are mandatory to optimize IBC management, considering factors such as tumor's molecular profile.

SMAD3, Cell proliferation and lymph nodes metastasis in breast cancer hormone-dependent.

INTRODUCTION: Tumor Growth Factor-ß (TGF-ß) is a multifunctional cytokine that plays a crucial role in various biological processes. TGF-ß is also involved in various pathologies including breast cancer (BC). BC is strongly dependent on hormone receptors such as Estrogen receptors (ERa, ERb) and Progesterone Receptor (PR). AIM: To audit the potential cross-talk between TGF-ß and the molecular distribution of hormone receptors (ERs and PR). METHODS: The current study analyzes the expression patterns of SMAD3, ERα, ERß and PR in 40 breast tumor tissues using qRT-PCR. Furthermore, the Ki-67 and HER2/neu status have been detected by Immunohistochemistry. RESULTS: Our results show a decrease in the SMAD3 expression in 27 of the 40 cases while its expression is increased in the remaining 13 cases (p=0.003). The over-expression of SMAD3 is associated with high tumor grades. Moreover, there is a significant positive correlation between SMAD3+ with a high proliferative index and metastases (p=0.001 and p=0.01respectevely). The SMAD3 expression relative to (ERα, ERß) subgroups shows a significant association of SMAD3+ with the (ERα+, ERß+) subgroups (p=0.009). The same is true for PR, our results show a significant association of SMAD3+ with PR+ (p=0.02). Moreover, analysis of the expression of molecular subgroups (SMAD3+, ERα+, ERß+) and (SMAD3+, PR+) compared to clinical and pathological information shows a significant association with high grade tumors, a high proliferation index (p=0.02, p= 0.01 respectively) and lymph node infiltration. CONCLUSION: It is concluded that SMAD3 can promote cell proliferation and metastases in (ERα+, ERß+) and PR+ breast cancer.

Surgical resection of a massive residual retroperitoneal mass after chemotherapy for a paratesticular rhabdomyosarcoma: a case report.

INTRODUCTION: Paratesticular rhabdomyosarcoma is a rare and aggressive mesenchymal tumor, accounting for only 7% of all rhabdomyosarcomas. It is mainly encountered in children and adolescents. The standard treatment consists of radical orchidectomy with negative surgical margins. However, chemotherapy is recommended to control retroperitoneal micrometastasis. The place of surgery for progressive retroperitoneal lymph node metastases remains controversial. We present a case of paratesticular rhabdomyosarcoma with progressive retroperitoneal lymph node metastases treated with surgery. CASE REPORT: We report a case of a 17-year-old North African male with no particular medical history who presented with a left scrotal mass that had been evolving for several months. Beta-human chorionic gonadotropin, alpha-fetoprotein, and lactate dehydrogenase were normal. Scrotal ultrasonography revealed the presence of a 6 cm heterogeneous hypoechogenic tissular mass with cystic areas adherent to the left scrotal wall, which was thickened in some places and vascularized by color Doppler. It exerted a mass effect on the homolateral testicle, which was of average volume. The thoracic-abdominal-pelvic computed tomography scan showed the presence of suspicious paraaortic lymph nodes. The most voluminous one measured 16 × 23 mm2. A left orchidectomy was performed. The final pathology report revealed an 8 cm paratesticular rhabdomyosarcoma of the embryonic type that displaced the testicle without invading it. Without going beyond it, it infiltrated the epididymis, the rete testis, and the albuginea. The surgical margin at the level of the spermatic cord was free. The patient had adjuvant chemotherapy (ifosfamide, vincristine, and dactinomycin). The patient had a challenging paraaortic lymph node dissection since the mass enlaced the left ureter and renal vessels. On histological examination, the paraaortic lymph nodes were metastatic. CONCLUSION: Rhabdomyosarcoma is an aggressive malignancy with high metastatic potential. Therefore, only an accurate diagnosis and early treatment can ensure better survival. Surgery in expert hands seems to be a good option for progressive retroperitoneal nodes. However, further studies are needed to determine the place of surgery in this setting.

STAT-5 and STAT-6 in Breast Cancer: Potential Crosstalk With Estrogen and Progesterone Receptors Can Affect Cell Proliferation and Metastasis.

Background: Signal transducers and activators of transcription 5a and 6 (STAT5a and STAT6) play a critical role in tumorigenesis of mammary glands. Based on previous studies, the breast cancer is largely dependent on hormone receptors. Consequently, it is very interesting to decipher the relationship between the STAT5a and STAT6 expression and the molecular distribution of estrogen receptors (ERs) and progesterone receptors (PRs) in mammary tumors. Methods: Our study analyzed the expression of STAT5a and STAT6, ERα, ERß and PR in 40 breast tumor tissues using quantitative real-time polymerase chain reaction (qRT-PCR). Furthermore, the Ki-67 and HER2 status were detected using immunohistochemistry. Results: STAT5a and STAT6 were retained in the majority of the cases studied. Increasing of STAT5a and STAT6 is significantly associated with ERs and PR. The coexpression of both STAT5a and STAT6 with ERs and PR is associated with high tumor grades. Moreover, the coexpression of STAT5a and STAT6 with ERα and PR is associated with a high proliferation index. In addition, (STAT6 + ERß+) and (STAT6 + PR+) breast cancer subgroups are associated with lymph node infiltration (P = 0.001 and P = 0.03, respectively). Conclusions: Our study results provide an interaction between STAT5a and STAT6 with ERs and PR inducing cell proliferation. Coexpression of STAT5a and STAT6 with ERs and PR can predict sensibility to hormonal therapy.

MARCKS as a Potential Therapeutic Target in Inflammatory Breast Cancer.

Inflammatory breast cancer (IBC) is the most pro-metastatic form of breast cancer (BC). We previously demonstrated that protein overexpression of Myristoylated Alanine-Rich C Kinase Substrate (MARCKS) protein was associated with shorter survival in IBC patients. MARCKS has been associated with the PI3K/AKT pathway. MARCKS inhibitors are in development. Our objective was to investigate MARCKS, expressed preferentially in IBC that non-IBC (nIBC), as a novel potential therapeutic target for IBC. The biologic activity of MPS, a MARCKS peptide inhibitor, on cell proliferation, migration, invasion, and mammosphere formation was evaluated in IBC (SUM149 and SUM190) and nIBC (MDA-MB-231 and MCF7) cell lines, as well as its effects on protein expression in the PTEN/AKT and MAPK pathways. The prognostic relevance of MARCKS and phosphatase and tensin homolog (PTEN) protein expression as a surrogate marker of metastasis-free survival (MFS) was evaluated by immunohistochemistry (IHC) in a retrospective series of archival tumor samples derived from 180 IBC patients and 355 nIBC patients. In vitro MPS impaired cell proliferation, migration and invasion, and mammosphere formation in IBC cells. MARCKS inhibition upregulated PTEN and downregulated pAKT and pMAPK expression in IBC cells, but not in nIBC cells. By IHC, MARCKS expression and PTEN expression were negatively correlated in IBC samples and were associated with shorter MFS and longer MFS, respectively, in multivariate analysis. The combination of MARCKS-/PTEN+ protein status was associated with longer MFS in IBC patient only (p = 8.7 × 10-3), and mirrored the molecular profile (MARCKS-downregulated/PTEN-upregulated) of MPS-treated IBC cell lines. In conclusion, our results uncover a functional role of MARCKS implicated in IBC aggressiveness. Associated with the good-prognosis value of the MARCKS-/PTEN+ protein status that mirrors the molecular profile of MPS-treated IBC cell lines, our results suggest that MARCKS could be a potential therapeutic target in patients with MARCKS-positive IBC. Future preclinical studies using a larger panel of IBC cell lines, animal models and analysis of a larger series of clinical samples are warranted in order to validate our results.

Gayet-Wernicke's encephalopathy complicating prolonged parenteral nutrition in patient treated for colonic cancer - a case report.

BACKGROUND: Gayet-Wernicke's encephalopathy (GWE) is a neurological pathology caused by a Thiamine deficiency. While it is most often related to chronic alcoholism, GWE can occur in any situation that results in thiamine deficiency. It is a fairly common pathology that is frequently underdiagnosed and therefore under-treated, and is associated with a high mortality and morbidity rate. In the absence of pathognomonic signs, the diagnosis of GWE relies on a range of clinical, biological and radiological assessments. GWE is considered a medical emergency. We present a case of Gayet-Wernicke's Encephalopathy resulting from complete parenteral nutrition in an undernourished North African male operated for a left colon tumor. Through this report, our aim was to put the light on this often underknown disease and to remind the interest of thinking about this pathology in patients at risk of undernourishment especially in oncology. CASE PRESENTATION: A 66-year-old North African male with no personal or family history was operated for a sigmoid colon tumor. He was put on exclusive parenteral nutrition on day thirteen post-operatively and presented with a GWE on day sixteen post-operatively. The patient was treated with intravenous vitamin B1 on day eighteen post-operatively and deceased on day twenty-four post-operatively. CONCLUSIONS: Although most often associated with chronic alcoholism, GWE occurs in any situation where there is an increased energy demand or decreased nutritional intake especially in oncology. GWE is common but under-diagnosed and remains lethal if not treated urgently, hence the importance of prophylactic treatment.

Association of ZEB1 and Vimentin with poor prognosis in metaplastic breast cancer.

Zinc finger E-box binding homeobox factor 1 (ZEB1) is a transcription factor involved in the epithelial to mesenchymal transition (EMT) process of metaplastic breast cancer (MBC). This study aimed to assess the expression of ZEB1 in MBC and explore its association with clinicopathological factors and prognosis. We analyzed the immunohistochemical expression of ZEB1 in 50 MBC tissue samples. ZEB1 was overexpressed in 36% (18/50) of cases. ZEB1 overexpression was significantly correlated to fibromatosis-like and spindle cell sarcoma subtypes (P < 0.001) and tended to be correlated to metastatic status (P = 0.069). Using the Kaplan-Meier method, ZEB1 expression was significantly associated with poor 5-years overall survival (OS) (P = 0.001) and relapse-free survival (RFS) (P = 0.0001). The multivariate Cox regression analysis showed that ZEB1 positive remained a significantly independent adverse prognostic factor for RFS and OS (HR = 4.9 [2.14-11.53]; P < 0.0001) and (HR = 4 [1.05-15.18]; P = 0.042), while Vimentin was an independent poor prognostic factor only for RFS (HR = 5.69 [1.79-18.11], P = 0.003). Our results indicated that ZEB1 and Vimentin overexpression might serve as adverse prognostic factors and potential therapeutic targets for MBC patients.

Survival After Pelvic Exenteration for Cervical Cancer.

BACKGROUND: The purpose of this work was to identify the results of pelvic exenteration for recurrent, persistent or locally advanced cervical cancer in terms of survival performed for 41 patients in Salah Azaiez Institute. PATIENTS AND METHODS: We conducted a retrospective unicentric study. The association between PE and OS was estimated using the method of Kaplan-Meier using SPSS ver 24. RESULTS: Median age at the time of intervention was 53.9 years old. FIGO stage IIB was the most frequent (46.3%). Eighteen patients had pelvic exenteration after neoadjuvant treatment. Resection margins were free of tumor in 83.3% of cases. Twenty-three patients underwent pelvic exenteration for recurrence of cervical cancer treated. The median time of recurrence was 23.4 months. Free resection margins were obtained in 69.5% of cases. Postoperative complications were noted in 61% of patients. Two deaths were seen in the early postoperative period. After a median follow-up of 40.5 months, 24.4% of recurrences were noted. Overall survival at 5 years was 51% and recurrence-free survival at one year was 39%. Prognostic factors which impact overall and recurrence-free survival were the size of recurrence and resection margins after exenteration. The time between the end of initial treatment and recurrence was the only predictive factor of recurrence after pelvic exenteration. CONCLUSION: Pelvic exenteration remains a curative treatment of cervical cancer in certain indications despite high morbidity. A rigorous preoperative selection of candidate may reduce the morbidity and improve the survival of patients.

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.

Identification of BRCA2 Cis Double Heterozygous Breast Cancer Cases Using Whole Exome Sequencing: Phenotypic Expression and Impact on Personalized Oncology.

BRCA1 and BRCA2 are the most commonly mutated breast cancer susceptibility genes that convey a high risk of breast and ovarian cancer. Most BRCA1 or BRCA2 mutation carriers have inherited a single heterozygous mutation. In recent years, very rare cases with biallelic or trans double heterozygous mutations on BRCA1 and or BRCA2 have been identified and seem to be associated with distinctive phenotypes. Given that this genotype-phenotype correlation in cancer predisposing hereditary conditions is of relevance for oncological prevention and genetic testing, it is important to investigate these rare BRCA genotypes for better clinical management of BRCA mutation carriers. Here we present the first report on Cis double heterozygosity (Cis DH) on BRCA2 gene identified using Whole exome sequencing (WES) in a Tunisian family with two BRCA2 mutations namely: c.632-1G>A and c.1310_1313DelAAGA that are both reported as pathogenic in ClinVar database. Subsequent analysis in 300 high-risk Tunisian breast cancer families detected this Cis double heterozygous genotype in 8 additional individuals belonging to 5 families from the same geographic origin suggesting a founder effect. Moreover, the observed Cis DH seems to be associated with an early age of onset (mean age = 35.33 years) and severe phenotype of the disease with high breast cancer grade and multiple cancer cases in the family. The identification of unusual BRCA genotypes in this Tunisian cohort highlights the importance of performing genetic studies in under-investigated populations. This will also potentially help avoiding erroneous classifications of genetic variants in African population and therefore avoiding clinical misdiagnosis of BRCA related cancers. Our findings will also have an impact on the genetic testing and the clinical management of North African breast cancer patients as well as patients from different other ethnic groups in regard to several emerging target therapies such as PARP inhibitors.

Chemoradiotherapy or chemotherapy as adjuvant treatment for resected gastric cancer: should we use selection criteria?

BACKGROUND: The management of gastric adenocarcinoma is essentially based on surgery followed by adjuvant treatment. Adjuvant chemotherapy (CT) as well as chemoradiotherapy (CTRT) have proven their effectiveness in survival outcomes compared to surgery alone. However, there is little data comparing the two adjuvant approaches. This study aimed to compare the prognosis and survival outcomes of patients with gastric adenocarcinoma operated and treated by adjuvant radio-chemotherapy or chemotherapy. MATERIALS AND METHODS: We retrospectively evaluated 80 patients with locally advanced gastric cancer (LGC) who received adjuvant treatment. We compared survival outcomes and patterns of recurrence of 53 patients treated by CTRT and those of 27 patients treated by CT. RESULTS: After a median follow-up of 38.48 months, CTRT resulted in a significant improvement of the 5-year PFS (60.9% vs. 36%, p = 0.03) and the 5-year OS (55.9% vs. 33%, p = 0.015) compared to adjuvant CT. The 5-year OS was significantly increased by adjuvant CTRT (p = 0.046) in patients with lymph node metastasis, and particularly those with advanced pN stage (p = 0.0078) and high lymph node ratio (LNR) exceeding 25% (p = 0.012). Also, there was a significant improvement of the PFS of patients classified pN2-N3 (p = 0.022) with a high LNR (p = 0.018). CTRT was also associated with improved OS and PFS in patients with lymphovascular and perineural invasion (LVI and PNI) compared to chemotherapy. CONCLUSION: There is a particular survival benefit of adding radiotherapy to chemotherapy in patients with selected criteria such as lymph node involvement, high LNR LVI, and PNI.

Intraabdominal lesser sac metastasis from Ewing's sarcoma: An exceptional localization.

Ewing's sarcoma/primitive neuroectodermal tumor is rare and aggressive with a poor prognosis. Intraabdominal metastases are an uncommon condition. Metastasis in the lesser sac is an exceptional occurrence. To the best of our knowledge, this location has not been described previously. We report a case of a 15-year-old patient treated for Ewing's sarcoma of the left arm 6 years back. She had developed a suspicious mass in the lesser sac 6 years following her primary tumor. The histopathologic exam revealed a tumor with "small round cells" that were positive for CD99, confirming the relapse of Ewing's sarcoma. The relapse was successfully managed with chemotherapy and surgery. Intraabdominal, extraintestinal masses in patients treated previously for Ewing's sarcoma should be considered as Ewing's sarcoma relapse in the differential diagnosis. We fully describe the management of this atypical relapse, with different components of clinical, radiological, and histological findings.

Colo-colic intussusception secondary to colon lipoma: A case report.

INTRODUCTION AND IMPORTANCE: Intestinal intussusception is rare in adults and it is associated with lead points affecting the colon in around 17% of patients. Lipomas are very rare benign tumors which may act as lead points for intestinal intussusception. Indeed, the incidence of intestinal intussusception is much rare when caused by lipomas. CASE PRESENTATION: Our patient is a 29-year-old male, previously healthy and admitted for severe right lower quadrant abdominal pain of 2-day duration. Computed tomography (CT) scan of the abdomen and pelvis showed large mass of fat consistency containing colon structure. CLINICAL DISCUSSION: Urgent laparotomy was opted during which colo-colic intussusception was diagnosed and right hemicolectomy with primary ileocolic anastomosis was performed. Pathology report showed that intussusception was induced by a colon lipoma. Patient had an uneventful hospital stay and was discharged on post-operative day 5. CONCLUSION: Thus we recommend that colo-colic intussusception caused by lipoma be considered in the differential when diagnosing adults with right lower quadrant pain.

Germline copy number variations in BRCA1/2 negative families: Role in the molecular etiology of hereditary breast cancer in Tunisia.

Hereditary breast cancer accounts for 5-10% of all breast cancer cases. So far, known genetic risk factors account for only 50% of the breast cancer genetic component and almost a quarter of hereditary cases are carriers of pathogenic mutations in BRCA1/2 genes. Hence, the genetic basis for a significant fraction of familial cases remains unsolved. This missing heritability may be explained in part by Copy Number Variations (CNVs). We herein aimed to evaluate the contribution of CNVs to hereditary breast cancer in Tunisia. Whole exome sequencing was performed for 9 BRCA negative cases with a strong family history of breast cancer and 10 matched controls. CNVs were called using the ExomeDepth R-package and investigated by pathway analysis and web-based bioinformatic tools. Overall, 483 CNVs have been identified in breast cancer patients. Rare CNVs affecting cancer genes were detected, of special interest were those disrupting APC2, POU5F1, DOCK8, KANSL1, TMTC3 and the mismatch repair gene PMS2. In addition, common CNVs known to be associated with breast cancer risk have also been identified including CNVs on APOBECA/B, UGT2B17 and GSTT1 genes. Whereas those disrupting SULT1A1 and UGT2B15 seem to correlate with good clinical response to tamoxifen. Our study revealed new insights regarding CNVs and breast cancer risk in the Tunisian population. These findings suggest that rare and common CNVs may contribute to disease susceptibility. Those affecting mismatch repair genes are of interest and require additional attention since it may help to select candidates for immunotherapy leading to better outcomes.

Identification of Novel BRCA1 and RAD50 Mutations Associated With Breast Cancer Predisposition in Tunisian Patients.

BACKGROUND: Deleterious mutations on BRCA1/2 genes are known to confer high risk of developing breast and ovarian cancers. The identification of these mutations not only helped in selecting high risk individuals that need appropriate prevention approaches but also led to the development of the PARP-inhibitors targeted therapy. This study aims to assess the prevalence of the most frequent BRCA1 mutation in Tunisia, c.211dupA, and provide evidence of its common origin as well as its clinicopathological characteristics. We also aimed to identify additional actionable variants using classical and next generation sequencing technologies (NGS) which would allow to implement cost-effective genetic testing in limited resource countries. PATIENTS AND METHODS: Using sanger sequencing, 112 breast cancer families were screened for c.211dupA. A set of patients that do not carry this mutation were investigated using NGS. Haplotype analysis was performed to assess the founder effect and to estimate the age of this mutation. Correlations between genetic and clinical data were also performed. RESULTS: The c.211dupA mutation was identified in 8 carriers and a novel private BRCA1 mutation, c.2418dupA, was identified in one carrier. Both mutations are likely specific to North-Eastern Tunisia. Haplotype analysis supported the founder effect of c.211dupA and showed its recent origin. Phenotype-genotype correlation showed that both BRCA1 mutations seem to be associated with a severe phenotype. Whole Exome Sequencing (WES) analysis of a BRCA negative family revealed a Variant of Unknown Significance, c.3647C > G on RAD50. Molecular modeling showed that this variant could be classified as deleterious as it is responsible for destabilizing the RAD50 protein structure. Variant prioritization and pathway analysis of the WES data showed additional interesting candidate genes including MITF and ANKS6. CONCLUSION: We recommend the prioritization of BRCA1-c.211dupA screening in high risk breast cancer families originating from the North-East of Tunisia. We also highlighted the importance of NGS in detecting novel mutations, such as RAD50-c.3647C > G. In addition, we strongly recommend using data from different ethnic groups to review the pathogenicity of this variant and reconsider its classification in ClinVar.

Surgical approach for duodenal diverticulum perforation: A case report.

INTRODUCTION: Duodenal Diverticula is not uncommon and it is mostly found in the 2nd part of the duodenum. Despite the fact that it is mostly found incidentally, it can complicate however it rarely complicates by perforation. Treatment is indicated only in complicated cases and it is divided into conservative and surgical arms. PRESENTATION OF CASE: It is a case of 78 years old Lebanese female that was diagnosed intra-operatively with a perforated duodenal diverticulum after presenting with post prandial abdominal pain, distention and pneumoperitoneum on imaging. Our case was consistent with previous reports where the diverticulum occurred in the second part of the duodenum. We opted for primary resection of the diverticulum and over-sewing. Moreover, patient had an uneventful post-operative course and progressed gradually to be discharged on day 10. CONCLUSION: Our case aims to draw attention to a rare complication of duodenal diverticula and to widen the differential diagnosis of pneumoperitoneum thus concluding about the better treatment option. Previous reports show that proper management is still a controversial topic; however surgical approach is indicated in case of systemic signs.

Tumor DNA hypomethylation of LINE-1 is associated with low tumor grade of breast cancer in Tunisian patients.

DNA hypomethylation of long interspersed repetitive DNA retrotransposon (LINE-1) and Alu repeats elements of short interspersed elements family (SINEs) is an early event in carcinogenesis that causes transcriptional activation and leads to chromosomal instability. In the current study, DNA methylation levels of LINE-1 and Alu repeats were analyzed in tumoral tissues of invasive breast cancer in a Tunisian cohort and its association with the clinicopathological features of patients was defined. DNA methylation of LINE-1 and Alu repeats were analyzed using pyrosequencing in 61 invasive breast cancers. Median values observed for DNA methylation of LINE-1 and Alu repeats were considered as the cut-off (59.81 and 18.49%, respectively). The results of the current study demonstrated a positive correlation between DNA methylation levels of LINE-1 and Alu repeats (rho=0.284; P<0.03). DNA hypomethylation of LINE-1 was also indicated to be associated with low grade (P=0.023). To the best of our knowledge, the current study is the first study regarding DNA methylation of LINE-1 and Alu repeats element in breast cancer of the Tunisian population. The results of the current study suggest that, since hypomethylation of LINE-1 is associated with low grade, it could be used as a biomarker for prognosis for patients with breast cancer.

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.

Generalized cutaneous metastases of breast cancer: An uncommon presentation.

Cutaneous metastases are rare and represent a sign of poor prognosis. They are a sign of widespread disease. Breast cancer is the most common neoplasm leading to their appearance. Palliative care is the treatment of choice.

Pure Ductal Carcinoma in Situ in The Male Breast: A Rare Entity.

Pure ductal carcinoma in situ of male breast (DCIS) is extremely rare. Only a few cases have been reported until now. Its treatment is not well established. Prognosis is as good as in women. In this study, we reported 3 cases of pure ductal carcinoma in situ in the male breast. The mean age of DCIS patients was 58.3 years. The main symptom was a breast mass. The median size of the tumor was 25 mm. Two patients had an axillary lymph node. The left side was reached in 2 cases. All of the patients underwent mastectomy. The histopathological assessment showed papillary, cribriform, and comedocarcinoma in situ. There was no evidence of invasive carcinoma. In one case, the DCIS was associated with Paget's disease of the nipple. One patient received hormonotherapy. The time of follow-up ranged between 6 and 117 months. One patient developed an invasive recurrence.