MicroRNA Expression Profiling on Paired Primary and Lymph Node Metastatic Breast Cancer Revealed Distinct microRNA Profile Associated With LNM.

Breast cancer (BC) is the foremost cause of cancer-related deaths in women. BC patients are oftentimes presented with lymph node metastasis (LNM), which increases their risk of recurrence. Compelling data have recently implicated microRNAs in promoting BC metastasis. Therefore, the identification of microRNA (miRNA)-based molecular signature associated with LNM could provide an opportunity for a more personalized treatment for BC patients with high risk of LNM. In current study, we performed comprehensive miRNA profiling in matched primary breast and LNM and identified 40 miRNAs, which were differentially expressed in LNM compared to primary tumors. The expression of 14 miRNAs (Up: hsa-miR-155-5p, hsa-miR-150-5p, hsa-miR-146a-5p, hsa-miR-142-5p and down: hsa-miR-200a-3p, hsa-miR-200b-3p, hsa-miR-200c-3p, hsa-miR-205-5p, hsa-miR-210-3p, hsa-miR-214-3p, hsa-miR-141-3p, hsa-miR-127-3p, hsa-miR-125a-5p, and hsa-let-7c-5p) was subsequently validated in a second cohort of 32 breast and 32 matched LNM tumor tissues. Mechanistically, forced expression of hsa-miR-205-5p, or hsa-miR-214-3p epigenetically inhibited MDA-MB-231 cell proliferation, colony formation, and cell migration. Global gene expression profiling on MDA-MB-231 cells overexpressing hsa-miR-205-5p, or hsa-miR-214-3p in combination with in silico target prediction and ingenuity pathway analyses identified multiple bona fide targets for hsa-miR-205-5p, hsa-miR-214-3p affecting cellular proliferation and migration. Interestingly, interrogation of the expression levels of hsa-miR-205 and hsa-miR-214 in the METABRIC breast cancer dataset revealed significantly poor overall survival in patients with downregulated expression of miR-205 [HR = 0.75 (0.61-0.91)], p = 0.003 and hsa-miR-214 [HR = 0.74 (0.59-0.93) p = 0.008]. Our data unraveled the miRNA-transcriptional landscape associated with LNM and provide novel insight on the role of several miRNAs in promoting BC LNM, and suggest their potential utilization in the clinical management of BC patients.

Atypical diffuse bilateral cystic lung changes secondary to erlotinib treatment in a patient with metastatic non-small cell lung carcinoma: A case report and literature review.

Erlotinib is a first-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) approved in the first-line treatment of advanced non-small-cell lung cancer (NSCLC) patients with sensitizing epidermal growth factor receptor (EGFR) mutations. The response rate to erlotinib is ~60% and the incidence of erlotinib-induced interstitial lung disease (ILD) is ~1-4%. The Response Evaluation Criteria in Solid Tumours (RECIST) tool is commonly used to assess response to erlotinib; however, evaluation of response and subsequent progression in the presence of atypical cystic lung changes may be challenging. We herein present a rare case of diffuse cystic lung changes secondary to erlotinib treatment in a patient with EGFR mutation-positive metastatic NSCLC. Challenges in assessing atypical tumour response to erlotinib, pitfalls in using RECIST and differential diagnosis of TKI-related ILD are discussed in detail.

Efficacy of Nivolumab in a Patient with Metastatic Renal Cell Carcinoma and End-Stage Renal Disease on Dialysis: Case Report and Literature Review.

Treatment of patients with metastatic renal cell carcinoma (mRCC) and end-stage renal disease (ESRD) on dialysis poses a therapeutic challenge, particularly as this patient group was excluded from the pivotal clinical trials. In addition, there is uncertainty regarding drug dosing/pharmacokinetics, lack of safety and efficacy data, and potential for increased toxicity when using targeted therapy or immunotherapy for the management of patients with mRCC on dialysis. Nivolumab, an anti-programmed death-1 immune checkpoint inhibitor antibody, is indicated for the treatment of patients with mRCC who have received prior antiangiogenic therapy. Given the above-mentioned uncertainties, clinicians may be reluctant to use nivolumab for this patient population, leading to potential denial of life-prolonging medications. We report the case of a 72-year-old gentleman with mRCC and ESRD on dialysis who received second-line nivolumab therapy and achieved an excellent symptomatic and radiological response, remaining progression-free for over 22 months. In addition, we have reviewed the pharmacokinetic data and published retrospective case studies to review the management options for patients with mRCC and ESRD on dialysis.

Rare Case of Intracardiac Renal Cell Carcinoma Metastasis with Response to Nivolumab: Case Report and Literature Review.

Intracardiac metastases in the absence of inferior vena cava involvement is a rare occurrence in patients with metastatic renal cell carcinoma (mRCC). There is limited evidence regarding the efficacy and safety of standard treatment modalities for mRCC patients with intracardiac metastases. Presence of intracardiac metastases is known to indicate poor prognosis and may potentially increase risk of treatment-related complications. Recent advances in RCC management have integrated nivolumab, a programmed death-1 (PD-1) receptor inhibitor, as a preferred treatment option in the second-line setting after failure of prior anti-angiogenic therapy; or in combination with ipilimumab, an anti-Cytotoxic T-lymphocyte antigen-4 antibody as first-line therapy for intermediate to poor risk patients with mRCC. The efficacy and toxicity of nivolumab in patients with mRCC and intracardiac metastases has never been reported previously. We herein present the first reported case of mRCC with intracardiac metastasis and a resultant excellent response to nivolumab treatment and discuss the imaging techniques and treatment options for this rare presentation.

Triple Negative Breast Cancer: A Tale of Two Decades.

Triple negative breast cancer (TNBC) is a heterogeneous disease entity constituting about 15% of breast cancer cases worldwide. TNBC is associated with poor prognosis and lack of sustained response to conventional chemotherapeutic agents. Tumoral heterogeneity and the presence of several subtypes of TNBC such as Basal like (BL)-1, BL-2, immune-modulatory, luminal androgen receptor, mesenchymal, and mesenchymal/stem like subtype and claudin low subtype, may explain some of the difficulties faced in managing this challenging disease subgroups. Although no approved targeted therapy is available for TNBCs, molecular-profiling efforts have revealed promising molecular targets such as the vascular endothelial growth factor (VEGF), epidermal growth factor receptor (EGFR), polyadenosine ribose polymerase inhibitors (PARPi) and DNA repair pathway, androgen pathway, and NOTCH pathway. TNBC is subject to intense research activities aiming at dissecting potential pathways, identifying potential molecular signatures and biomarkers in order to properly develop new targeted biologic modifiers. Despite this, there is a lack of approved predictive and prognostic biomarkers, and keeping in view the complexity of TNBC biology, research should be targeted towards identifying multi-factorial signatures rather than single markers. This review aims to summarize the current evidence, ongoing research and discuss future strategies for the treatment of patients with TNBC. In addition we have reviewed the recent advances in detecting predictive and prognostic biomarkers and identifying surrogate markers for early identification of potential responders to the new therapies.

microRNA expression profiling on individual breast cancer patients identifies novel panel of circulating microRNA for early detection.

Breast cancer (BC) is the most common cancer type and the second cause of cancer-related death among women. Therefore, better understanding of breast cancer tumor biology and the identification of novel biomarkers is essential for the early diagnosis and for better disease stratification and management choices. Herein we developed a novel approach which relies on the isolation of circulating microRNAs through an enrichment step using speed-vacuum concentration which resulted in 5-fold increase in microRNA abundance. Global miRNA microarray expression profiling performed on individual samples from 23 BC and 9 normals identified 18 up-regulated miRNAs in BC patients (p(corr) < 0.05). Nine miRNAs (hsa-miR-4270, hsa-miR-1225-5p, hsa-miR-188-5p, hsa-miR-1202, hsa-miR-4281, hsa-miR-1207-5p, hsa-miR-642b-3p, hsa-miR-1290, and hsa-miR-3141) were subsequently validated using qRT-PCR in a cohort of 46 BC and 14 controls. The expression of those microRNAs was overall higher in patients with stage I, II, and III, compared to stage IV, with potential utilization for early detection. The expression of this microRNA panel was slightly higher in the HER2 and TN compared to patients with luminal subtype. Therefore, we developed a novel approach which led to the identification of a novel microRNA panel which was upregulated in BC patients with potential utilization in disease diagnosis and stratification.

Breast cancer correlates in a cohort of breast screening program participants in Riyadh, KSA.

BACKGROUND: Breast cancer is the first cancer among females in the Kingdom of Saudi Arabia, accounting for 27.4% of all newly diagnosed female cancers in 2010. There are several risk factors affecting the incidence of breast cancer where some factors influence the risk more than the others. AIM: We aimed to identify the different risk factors related to breast cancer among females participating in the breast-screening program in Riyadh, KSA. METHODS: Based on data from phase-I of the breast-screening program, a case-control study was conducted on women living in Riyadh, KSA. A sample of 349 women (58 cases and 290 controls) was recruited to examine the different breast cancer correlates. Multivariate regression model was built to investigate the most important risk factors. RESULTS: The mean age of cases was 48.5±7.1 years. Age at marriage, number of pregnancy, age at menopause, oral contraceptive pills, breast feeding and family history of breast cancer in first-degree relative were identified as the most important correlates among the studied cohort. CONCLUSIONS: The findings of the current work suggested that age at marriage, age at menopause ⩾50 years and 1st degree family history of breast cancer were risk factors for breast cancer, while, age at menopause <50 years, number of pregnancies and practicing breast feeding were protective factors against breast cancer. There was no effect of body mass index or physical inactivity. Further studies are needed to explore the hereditary, familial and genetic background risk factors in Saudi population.

Determining circulating endothelial cells using CellSearch system during preoperative systemic chemotherapy in breast cancer patients.

BACKGROUND: Circulating endothelial cells (CECs) have been studied as a biomarker for tumour progression and monitoring therapeutic effects. The CellSearch system is a semi-automated system that allows standardised analysis of CECs. This study assessed the clinical implications of CECs determined by the CellSearch system in breast cancer patients. METHODS: Seventy-six consecutive breast cancer patients (53 operable and 23 metastatic or recurrent) were enrolled for the study. Thirty-five patients with operable breast cancer received preoperative chemotherapy with a regimen based on anthracycline and/or taxane. CECs are defined as CD146(+)CD105(+)CD45(-)DAPI(+) cells in the system. CD34 expression was examined using the additional channel in the system. RESULTS: A majority (4539 of 5183 cells, 88%) of CECs from patients with operable breast cancer were CD34-positive. Triple-negative cancers showed higher baseline CEC and CD34(+)CEC counts than the other types (P=0.0387 and 0.0377, respectively). Low baseline CEC and CD34(+)CEC counts, and a low CD34 positive rate were associated with pathological complete response (pCR) of preoperative chemotherapy in patients with primary breast cancer (P=0.046, 0.027 and 0.01, respectively). In multivariate analyses, the CD34 positive rate was significant for pCR (P=0.021). During preoperative chemotherapy, CEC and CD34(+)CEC counts before each cycle of chemotherapy increased with taxane-based regimens (P=0.0018 and 0.0008, respectively) but not with anthracycline-based regimens. CONCLUSIONS: Baseline CEC, in particular CD34(+)CEC, counts and the CD34 positive rate might be useful for the prediction of treatment response of preoperative chemotherapy in patients with operable breast cancer.