Current Problems

Information for Readers Publication date: April 2019 Source: Current Problems in Cancer, Volume 43, Issue 2 Author(s):

A six-microRNA signature predicts survival of patients with uterine corpus endometrial carcinoma Publication date: April 2019 Source: Current Problems in Cancer, Volume 43, Issue 2 Author(s): Yue Wang, Mu Xu, Qing Yang Abstract Uterine corpus endometrial carcinoma (UCEC) is one of the most common female gynecological malignant tumors that threaten women health seriously. MicroRNAs (miRNAs) has been proved to play critical roles in tumor pathogenesis and malignant progression. In this study, we aimed to explore a novel signature of microRNA expression for predicting the overall survival (OS) of patients with UCEC. The genome-wide miRNA expression profiles and relevant clinical characteristics of 348 patients with UCEC were downloaded from the Cancer Genome Atlas (TCGA) data portal and analyzed comprehensively. A total of 144 miRNAs were confirmed to be expressed differentially in tumor tissues. Among them, 6 miRNAs (hsa-mir-15a.MIMAT0000068, hsa-mir-142.MIMAT0000433, hsa-mir-142.MIMAT0000434, hsa-mir-3170.MIMAT0015045, hsa-mir-1976.MIMAT0009451, and hsa-mir-146a.MIMAT0000449) were validated to be significantly correlated with the OS of patients with UCEC. The risk indictor established by the 6-microRNA signature was proved be an independent prognostic factor (Hazard ratio = 0.391; 95% CI: 0.195-0.783; P = 0.008). In conclusion, we identified miRNAs that were correlated with the occurrence and progression of UCEC and established a 6-microRNA expression signature as a predictor for the OS of patients with UCEC.

Causal effect of obesity on gynecologic malignancies Publication date: April 2019 Source: Current Problems in Cancer, Volume 43, Issue 2 Author(s): Courtney Griffiths, Edward Jimenez, Eva Chalas Abstract Introduction Gynecologic malignancies are estimated to affect 110,070 women and will be the cause of death in approximately 32,120 in 2018. Endometrial cancer is among the most prevalent with 63,320 estimated new cases and approximately 11,350 deaths, followed by ovarian cancer with an estimate of 22,000 new cases and 14,000 deaths annually. Obesity is one of the most modifiable risk factors. Providers should engage in a multifaceted approach to patient education and healthcare to decrease the projected cases of obesity-related cancers. Background The literature demonstrates a significant link between obesity and the development of certain malignancies such as endometrial, pancreatic, and renal cancer. Specific mechanisms found to play a role in the development of these malignancies include alterations of the metabolic pathway attributed to lipid accumulation as well as a chronic inflammatory process. Obesity also predisposes patients to other medical comorbidities as well as a poorer prognosis once a diagnosis of cancer is established. Factors contributing to poorer prognosis include challenges with treatment planning, specifically pertaining to inappropriate chemotherapy dosing and delivery of radiation therapy. Surgical approach and perioperative management are similarly challenging in obese patients and are associated with increased risk of complications. Conclusion Obesity is a modifiable factor which is associated with an increased risk of cancer and poorer outcomes. Providers should educate patients on all health hazards of obesity, including increased risk of cancer, and encourage them to participate in a structured weight loss plan.

Comparison of CA125, HE4, and ROMA index for ovarian cancer diagnosis Publication date: April 2019 Source: Current Problems in Cancer, Volume 43, Issue 2 Author(s): Lei Zhang, Ying Chen, Ke Wang Abstract Objective In view of the high rate of misdiagnosis of ovarian cancer, our study aimed to compare the performances of serum levels of human epididymis secretory protein 4 (HE4) and cancer antigen 125 (CA125), as well as ROMA index in the diagnosis of ovarian cancer. Methods Three hundred and seventy-three patients who suffered ovarian cancer were selected in Tianjin Medical University Cancer Institute and Hospital from July 2016 to July 2017. Patients were divided into premenopause group and postmenopause group. Based on the results of pathologic examinations, patients were divided into malignant, benign, and borderline groups, which were further divided into different pathologic type groups. HE4 and CA125 serum levels in each patient were detected and the ROMA index was analyzed. ROC curve analysis was conducted to compare the performances of serum CA125, serum HE4, and ROMA index in the diagnosis of ovarian cancer. Results Proportion of postmenopausal patients in malignant group (65.2%) was significantly higher than that in the benign group (34.3%). Serum levels of CA125 and HE4, and ROMA index were higher in patients with different types of malignant tumor than those in corresponding benign group. Serum HE4, serum CA125, and ROMA index had better performance in the diagnosis of postmenopausal ovarian cancer than that of premenopausal ovarian cancer. The overall performance of ROMA and HE4 was better than that of CA125, but it was affected by pathologic types. Conclusions Serum HE4, serum CA125, and ROMA can be used to predict ovarian cancer. HE4 and ROMA have better performance than CA125 in most cases, but pathologic types can also affect them.

Laryngeal metastases from breast cancer: A rare clinical entity Publication date: April 2019 Source: Current Problems in Cancer, Volume 43, Issue 2 Author(s): Ritesh Kumar, Sumit Kumar, Ajay Gogia, Aanchal Kakkar, Sandeep R Mathur Breast cancer is the most common malignancy in females. The common site for metastases is bone, lungs, liver, and regional lymph nodes. Larynx as a metastatic site from breast cancer is extremely rare. The authors report a 63-year-old female treated for carcinoma of right breast 5 years back who presented with hoarseness of voice. Clinicoradiological examination revealed a soft tissue lesion in larynx. Pathological evaluation of the laryngeal lesion revealed metastases secondary to breast cancer. The patient received systemic chemotherapy and local radiotherapy. Patients with a history of breast cancer presenting with hoarseness and shortness of breath should not only be evaluated for laryngeal primary but also for metastases. This case is reported in view of rarity of the case with laryngeal metastases from breast cancer masquerading as primary laryngeal disease. To the best of our knowledge, less than 20 cases of laryngeal metastases from breast cancer had been reported in literature till date. Patients with a history of breast cancer presenting with hoarseness and shortness of breath should not only be evaluated for laryngeal primary but also for metastases. Once the diagnosis is confirmed, the treatment of laryngeal metastases is multidisciplinary. Recognizing metastatic disease and prompt early treatment are very important to improve the quality of life.

Association of elevated levels of C-reactive protein with breast cancer, breast cancer subtypes, and poor outcome Publication date: April 2019 Source: Current Problems in Cancer, Volume 43, Issue 2 Author(s): Raman Preet Kaur, Rubal, Raja Paramjeet Singh Banipal, Rajesh Vashistha, Monisha Dhiman, Anjana Munshi Abstract Background and Purpose: Inflammation and caner are linked in a bidirectional manner. C-reactive protein (CRP) is an important inflammatory marker. The aim of the study was to test whether the inflammatory marker, CRP at the time of diagnosis of breast cancer is associated with metastasis, recurrence, and death in breast cancer patients from Malwa region of Punjab where breast cancer is widely feared. Material and Methods: Two hundred and forty-two breast cancer patients and 242 age and sex matched controls were included in the study. CRP levels were estimated using fully automated bio analyzer Erba200. Follow up interviews were conducted at an interval of 3, 6, 9, 12, 15, 18, 21, 24, and 27 months to determine the outcome among breast cancer patients. Results: Elevated levels of CRP were found among the diseased in comparison with controls (P < 0.0001). Higher CRP levels associated significantly with poor outcome including metastasis and recurrence among breast cancer patients [P = 0.03; 95% confidence interval; odds ratio: 2.954 (0.9125-9.561)]. Conclusion: Elevated levels of CRP associated significantly with increased risk of breast cancer and poor outcome. CRP estimation may be a simple and inexpensive tool for the risk assessment and outcome of the disease in Malwa region of Punjab where incidence of breast cancer is reported to be very high.

Are preoperative serum CA15-3 levels different in breast cancer subgroups? Publication date: April 2019 Source: Current Problems in Cancer, Volume 43, Issue 2 Author(s): Murat Araz, Ismail Beypinar, Sinan Kazan, Fatih Inci, Mesut Celiker, Mukremin Uysal Purpose Breast cancer classifies to 4 major subgroups according to immunohistochemistry staining features as Luminal A, Luminal B, human epidermal growth factor receptor 2 overexpression, and Triple Negative. Cancer Antigen15-3 (CA15-3) is used as a tumor marker in breast cancer while its value in early stage and in breast cancer subgroups is still controversial. In this study, we aimed to investigate that whether it is or not differences of the serum preoperative CA15-3 levels in early breast cancer subgroups. Methods We retrospectively investigated medical records of 751 breast cancer patients who admitted to Afyon Kocatepe University Department of Medical Oncology between January 2010 and December 2016. Total 361 patients were included in this study. The cut off value of Ki-67 was used as 20 to distinguish between Luminal A from Luminal B subgroups. Cutoff values of CA15-3 were evaluated as 25U/mL. Results CA15-3 levels were not significantly different according to clinical features. Molecular subgroups were similar in CA15-3 levels (P = 0.666). Elevated levels of CA15-3 ≥ 25 U/mL were found 34 patients (20.5%) in Luminal A, 15 patients (28.3%) in Luminal B1, 15 patients (20.3%) in Luminal B2, 7 patients (25%) in human epidermal growth factor receptor 2 overexpressed and 9 patients (22.5%) in triple negative groups. Conclusion There was no relationship preoperative CA15-3 levels and breast cancer subgroups.

Everolimus plus endocrine vs endocrine therapy in treatment advanced ER+, HER2− breast cancer patients: A meta-analysis Publication date: April 2019 Source: Current Problems in Cancer, Volume 43, Issue 2 Author(s): Na Wang, Kai Wang, Ya-ting Liu, Fei-xue Song ABSTRACT The purpose of this review was to compare the efficacy and safety of everolimus plus endocrine therapy with endocrine therapy for hormone receptor-positive, human epidermal growth factor 2 negative advanced breast cancer patients. We comprehensively searched the PubMed, the Cochrane Library, EMBASE, Web of Science, Chinese biomedicine literature database, WanFang Data, CNKI, and VIP database for relevant articles. The retrieval time limit is from building the database to July 2018. The computer search was supplemented with a manual search of reference lists for all available review articles. We scanned references of all included studies for additional studies. We included 7 randomized trials involving 1527 patients. Meta-analysis results are as follows: Everolimus plus endocrine therapy group is significantly better than endocrine therapy group in progression-free survival and clinical benefit rate, (hazard ratio [HR] = 0.48, 95% confidence interval [CI 0.42-0.55], P < 0.00001) and (risk ratio = 1.9, 95% CI [1.60-2.26], P < 0.00001). But there was no significant difference between the 2 groups in overall response rate and time to definitive deterioration (risk ratio = 4.37, 95% CI [0.79-24.27], P = 0.21) and (HR = 0.74, 95% CI [0.49-1.11], P = 0.15). In terms of safety, the incidence rate in everolimus plus endocrine therapy was higher than that in endocrine therapy group. Most frequently reported adverse events associated with everolimus treatment were stomatitis, rash, fatigue, diarrhea, decreased appetite, cough, dyspnea, and pneumonitis. The incidences of grade 3-4 adverse events were stomatitis, fatigue, diarrhea, pneumonitis, and hyperglycemia. Everolimus increased the efficacy of endocrine therapy in treatment advanced endocrine receptor-positive, human epidermal growth factor 2 negative breast cancer patients, and the safety profile of the combination is acceptable.

Expressional analysis of MLH1 and MSH2 in breast cancer Publication date: April 2019 Source: Current Problems in Cancer, Volume 43, Issue 2 Author(s): Saima Shakil Malik, Nosheen Masood, Muhammad Asif, Parvez Ahmed, Zafar Ullah Shah, Jahangir Sarwar Khan Abstract Background Mismatch repair proteins are ubiquitous keys in diverse cellular functions and protects the genome by correcting mismatch as post replication error correction machinery. Mismatch repair deficiency was associated with tumor development and progression therefore, current study was aimed to investigate MLH1 and MSH2 expression in breast cancer and correlate patients' clinicopathological factors with status of mismatch repair genes. Material and methods Breast cancer tissues with adjacent normal tissue along with clinical details were collected during surgery from 80 cases. Immunohistochemistry was performed with primary and secondary antibodies for expressional analysis. Results were analyzed using SPSS version 24. Results Immunohistochemical analysis revealed that both MLH1 and MSH2 were crucial in maintaining DNA repair system and loss of these 2 mismatch repair proteins may lead to adverse outcomes in breast cancer. Statistically significant association was found between loss of MLH1 (P = 0.0004; odds ratio 13.8; 95% confidence interval 4.6-41.1), MSH2 (P = 0.0002; odds ratio 14.0; 95% confidence interval 4.7-42.2) and breast cancer. Statistical analysis demonstrated that MLH1 and MSH2 deficiency may lead breast cancer progression to advanced stage, correlated with tumor focality (MLH1 P = 0.001; MSH2 P = 0.002) and chemotherapy (MLH1 P = 0.01; MSH2 P = 0.04). Presence of CK7, GATA 3, and E cadherin tends to increase in mismatch repair deficient breast cancer. Whereas, no association of mismatch repair deficiency was observed with age, tumor grade, positive lymph nodes, menopause, and ER and/or PR status. Conclusion Loss of mismatch repair proteins in breast cancer highlights its potential role in DNA repair mechanisms and helps tumor cells to become resistant against chemotherapeutic drugs. Therefore, mismatch repair deficiency may contribute to breast cancer progression.

Table of Contents Publication date: April 2019 Source: Current Problems in Cancer, Volume 43, Issue 2 Author(s):