Ali Shamseddine

Effects of young age at presentation on survival in breast cancer

BackgroundYoung age remains a controversial issue as a prognostic factor in breast cancer. Debate includes patients from different parts of the world. Almost 50% of patients with breast cancer seen at the American University of Beirut Medical Center (AUBMC) are below age 50.MethodsWe reviewed 1320 patients seen at AUBMC between 1990 and 2001. We divided them in three age groups: Below 35, 35–50, and above 50. Data and survival were analyzed using Chi-square, Cox regression analysis, and Kaplan Meier.ResultsMean age at presentation was 50.8 years. 107 patients were below age 35, 526 between 35–50 and 687 patients above age 50. Disease stages were as follows: stage I: 14.4%, stage II: 59.9%, stage III: 20% and stage IV: 5.7%. Hormone receptors were positive in 71.8% of patients below 35, in 67.6% of patients 35–50 and in 78.3% of patients above 50. Grade of tumor was higher as age at presentation was lower. More young patients received anthracycline-based adjuvant chemotherapy. Of hormone receptor-positive patients, 83.8% of those below age 35 years, 87.76% of those aged 35–50 years, and 91.2% of those aged above 50 years received adjuvant tamoxifen. The mean follow up time was 3.7 +/- 2.9 years. Time to death was the only variable analyzed for survival analysis. Excluding stage IV patients, tumor size, lymph node, tumor grade and negative hormone receptors were inversely proportional to survival. Higher percentage of young patients at presentation developed metastasis (32.4% of patients below 35, as compared to 22.9% of patients 35–50 and 22.8% of patients above 50) and had a worse survival. Young age had a negative impact on survival of patients with positive axillary lymph nodes, and survival of patients with positive hormonal receptors, but not on survival of patients with negative lymph nodes, or patients with negative hormonal receptors.ConclusionYoung age at presentation conferred a worse prognosis in spite of a higher than expected positive hormone receptor status, more anthracycline-based adjuvant chemotherapy and equivalent adjuvant tamoxifen hormonal therapy in younger patients. This negative impact on survival was seen in patients with positive lymph nodes and those with positive hormonal receptors.

Secondary bile acids: an underrecognized cause of colon cancer

Bile acids were first proposed as carcinogens in 1939. Since then, accumulated evidence has linked exposure of cells of the gastrointestinal tract to repeated high physiologic levels of bile acids as an important risk factor for gastrointestinal cancers. High exposure to bile acids may occur in a number of settings, but most importantly, is prevalent among individuals who have a high dietary fat intake.A rapid effect on cells of high bile acid exposure is the generation of reactive oxygen species and reactive nitrogen species, disruption of the cell membrane and mitochondria, induction of DNA damage, mutation and apoptosis, and development of reduced apoptosis capability upon chronic exposure. Here, we review the substantial evidence of the mechanism of secondary bile acids and their role in colon cancer.

Loss of CD20 expression in relapsed lymphomas after rituximab therapy

Abstract: The response rate at relapse to rituximab in prior responders B‐cell non‐Hodgkins lymphoma (NHL) patients is below 50%. Loss of CD20 expression after rituximab therapy may explain this secondary resistance. However, the frequency of CD20 negative relapses cannot be assessed since most patients that relapsed after rituximab therapy have not been re‐biopsied. Here, we present two patients with CD20 positive low grade B‐cell NHL that lost the cell surface and cytoplasmic expression at relapse after rituximab therapy. Our findings suggest that confirmation of CD20 expression on the malignant B cells is required whenever rituximab therapy is considered.

Hypoxia-inducible factor in cancer angiogenesis: Structure, regulation and clinical perspectives

Tumor hypoxia is a common feature of many cancers. A master regulator of hypoxic response is the transcription factor hypoxia-inducible factor-1 (HIF-1). It functions as a master regulator of oxygen and undergoes conformational changes in response to varying oxygen concentrations. In this paper, we review what has been described about HIF-1: its structure, its regulation and target genes, its role in cancer, and its implication for cancer therapy.

Incidence and prophylaxis of venous thromboembolic events in multiple myeloma patients receiving immunomodulatory therapy

The diagnosis of multiple myeloma (MM) has been associated to an increased risk of venous thromboembolic events (VTE). Described risk factors that are not exclusive to MM include old age, chemotherapy, immobility, high levels of vascular endothelial growth factor, cancer procoagulant and paraproteinemia. Disease-specific risk factors unique to MM are production of procoagulant autoantibodies, a high incidence of acquired activated protein C resistance, increased levels of factor VIII and von Willebrand factor, and increased production of inflammatory cytokines, mainly IL-6, TNF and C-reactive protein. Treatment regimens that include thalidomide or related compounds such as lenalidomide combined with glucocorticoids and/or cytotoxic chemotherapy were associated with an increased risk of VTE. The risk appears to be particularly high when these immunomodulatory agents are combined with anthracyclines as treatment of newly-diagnosed disease. Combinations including thalidomide plus dexamethasone and/or alkylating agents are associated with an intermediate risk. The same regimens for relapsed/refractory myeloma seem to be associated with a lower risk. The use of newer immunomodulators such as brotezomib seem to reduce the thrombogenic potential. Several different thromboprophylaxis strategies have been effective in lowering the risk of VTE but the data are disputable. None of these VTE prevention strategies have been prospectively compared head-to-head.

Breast Cancer in Low- and Middle-Income Countries: An Emerging and Challenging Epidemic

Breast cancer is a major health care problem that affects more than one million women yearly. While it is traditionally thought of as a disease of the industrialized world, around 45% of breast cancer cases and 55% of breast cancer deaths occur in low and middle income countries. Managing breast cancer in low income countries poses a different set of challenges including access to screening, stage at presentation, adequacy of management and availability of therapeutic interventions. In this paper, we will review the challenges faced in the management of breast cancer in low and middle income countries.

Expression, prognostic and predictive impact of VEGF and bFGF in non-small cell lung cancer.

Despite major advances in cancer therapeutics, the prognosis for lung cancer patients is still poor and the median survival for patients presenting with advanced non-small cell lung cancer (NSCLC) is only 8-10 months. Angiogenesis is an important biological process and a relatively early event during lung cancer pathogenesis. Anti-angiogenic agents are used in treating patients with NSCLC, and their molecular biomarkers are also being assessed to predict response. A better understanding of the biology of angiogenesis in NSCLC may reveal new targets for treating this malignancy. In this article, we review the expression and prognostic impact of the angiogenic growth factors, vascular endothelial growth factor and basic fibroblast growth factor, in NSCLC.

Potential Targets for Colorectal Cancer Prevention

The step-wise development of colorectal neoplasia from adenoma to carcinoma suggests that specific interventions could delay or prevent the development of invasive cancer. Several key factors involved in colorectal cancer pathogenesis have already been identified including cyclooxygenase 2 (COX-2), nuclear factor kappa B (NF-κB), survivin and insulin-like growth factor-I (IGF-I). Clinical trials of COX-2 inhibitors have provided the “proof of principle” that inhibition of this enzyme can prevent the formation of colonic adenomas and potentially carcinomas, however concerns regarding the potential toxicity of these drugs have limited their use as a chemopreventative strategy. Curcumin, resveratrol and quercetin are chemopreventive agents that are able to suppress multiple signaling pathways involved in carcinogenesis and hence are attractive candidates for further research.

Update on totally implantable venous access devices

The use of totally implantable venous devices (TIVAD) has changed the care and quality of life for cancer patients, these devices allow chemotherapy administration, and blood sampling without the need for repeated venipuncture. These ports are used mainly when IV access is needed only intermittently over a long period of time. We are presenting a brief overview on TIVADs, with focus on the mid and long-term complications associated with these devices with their management.

Ratio Between Positive Lymph Nodes and Total Excised Axillary Lymph Nodes as an Independent Prognostic Factor for Overall Survival in Patients with Nonmetastatic Lymph Node-Positive Breast Cancer

Background.The status of the axillary lymph nodes in nonmetastatic lymph node-positive breast cancer (BC) patients remains the single most important determinant of overall survival (OS). Although the absolute number of nodes involved with cancer is important for prognosis, the role of the total number of excised nodes has received less emphasis. Thus, several studies have focused on the utility of the axillary lymph node ratio (ALNR) as an independent prognostic indicator of OS. However, most studies suffered from shortcomings, such as including patients who received neoadjuvant therapy or failing to consider the use of adjuvant therapy and tumor receptor status in their analysis.Methods.We conducted a single-center retrospective review of 669 patients with nonmetastatic lymph nodepositive BC. Data collected included patient demographics; breast cancer risk factors; tumor size, histopathological, receptor, and lymph node status; and treatment modalities used. Patients were subdivided into four groups according to ALNR value (<.25, .25–.49, .50–.74, .75–1.00). Study parameters were compared at the univariate and multivariate levels for their effect on OS.Results.On univariate analysis, both the absolute number of positive lymph nodes and the ALNR were significant predictors of OS. On multivariate analysis, only the ALNR remained an independent predictor of OS, with a 2.5-fold increased risk of dying at an ALNR of ≥.25.Conclusions.Our study demonstrates that ALNR is a stronger factor in predicting OS than the absolute number of positive axillary lymph nodes.