Evaluation of the outcome benefit conferred by intensive surveillance strategies in women with early-stage endometrial cancer

Introduction: The optimum follow-up regimen after treatment for early-stage endometrial cancer with curative intent is unknown. The National Comprehensive Cancer Network recommends a physical exam and vaginal cytology every three to six months for two years then at six to 12 month intervals with annual chest X-rays (CXR). However, there is debate as to whether intensive follow-up results in an improvement in outcomes for those with recurrent endometrial cancer. Objective: To determine if intensive surveillance for recurrent cancer in women with early-stage endometrial cancer improves their outcomes. Materials and Methods: The Roswell Park Cancer Institute tumor registry was used to identify patients with Stage I and II endometrial cancer initially diagnosed and treated over an 18-year period, who subsequently recurred. Clinico-pathological variables were abstracted. Patients were divided into two groups, depending on their mode of diagnosis of recurrent cancer: 1) routine screening, or 2) symptomatic. The outcomes between the two groups were compared. Results: Fifty-two patients met inclusion criteria. Twenty-three patients were diagnosed via routine screening methods and 29 were symptomatic at presentation. Groups were equally represented with respect to age, stage, grade, adjuvant therapy, site of recurrence (local, distant), and time to recurrence (p > 0.05). Median survival time was 79 months for those diagnosed during routine screening and 80 months for symptomatic patients (p > 0.05). Conclusion: Pap smear and CXR appear to be of limited utility as the present study has shown that women diagnosed as a result of intensive surveillance did not have a better outcome than those who presented when symptomatic

Clinicopathological characteristics and outcomes of rare histologic subtypes of gallbladder cancer over two decades: A population-based study.

BACKGROUND:There is limited literature about the clinicopathological characteristics and outcomes of rare histologic variants of gallbladder cancer (GBC). METHODS:Using SEER database, surgically managed GBC patients with microscopically confirmed adenocarcinoma, adenosquamous/squamous cell carcinoma and papillary carcinoma were identified from 1988 to 2009. Patients with second primary cancer and distant metastasis at presentation were excluded. The effect of clinicopathological variables on overall survival (OS) and disease specific survival (DSS) were analyzed using univariate and multivariate proportional hazards modeling. All associations were considered statistically significant at an alpha error of 0.01. RESULTS:Out of 4738 cases, 217 adenosquamous/squamous (4.6%), 367 papillary (7.7%), and 4154 adenocarcinomas (87.7%) were identified. Median age was 72 years. Higher tumor grade (grade 2, 3, 4 versus grade 1), higher T stage (T2, T3, T4 versus T1), lymph node positivity (N1 versus N0) and adenosquamous/squamous histology (versus adenocarcinoma) had worse OS and DSS (p < .001). Papillary GBC had better OS and DSS than adenocarcinoma (HR = 0.7; p < .001). Radical surgery (versus simple cholecystectomy) had better OS (HR = 0.83, p = 0.002) in multivariate analysis. OS rates at 3 and 5 years were 0.56 and 0.44 for papillary, 0.3 and 0.22 for adenocarcinoma, and 0.14 and 0.12 for adenosquamous/squamous histology, while DSS rates at 3 and 5 years were 0.67 and 0.61 for papillary, 0.38 and 0.31 for adenocarcinoma, and 0.17 and 0.16 for adenosquamous/squamous subtypes respectively. CONCLUSION:Papillary GBC had better survival outcomes while adenosquamous/squamous GBC had worse survival outcomes compared to gallbladder adenocarcinoma

Increased Expression Levels of WAVE3 Are Associated with the Progression and Metastasis of Triple Negative Breast Cancer

Background: Breast Cancer (BC) is a heterogeneous disease comprised of at least five genetically distinct subtypes, which together form the second leading cause of cancer death in women in the United States. Within BC subtypes, those classified as Triple Negative BCs (TNBCs) exhibit dismal survival rates due to their propensity to develop distant metastases. We have identified the WAVE3 protein, which is a critical regulator of actin cytoskeleton dynamics that are required for the motility and invasion of cancer cells through its activation of the Arp2/3 complex, as a key regulator of the different steps of the invasion-metastasis cascade in BC, especially in the more aggressive TNBCs. Our published studies have also shown that elevated expression levels of WAVE3 in the TNBC cell lines directly contribute to their increased invasion and metastasis potentials both in vitro and in vivo in murine models of BC metastasis.Methodology/Principal Findings: Herein, we utilized both immunohistochemistry (IHC) of primary human BC tumors as well as quantitative real-time RT-PCR of WAVE3 in the peripheral blood of BC patients to clearly establish that WAVE3 is a predictive marker of overall BC patients’ survival. High levels of WAVE3 were predictive for reduced distant recurrence-free survival as well as for decreased disease-specific mortality. Our analysis of WAVE3 expression levels in the peripheral blood of BC patients showed that WAVE3 is highly expressed in the blood of patients who developed metastatic breast cancer compared to those who did not. WAVE3 expression was also highly upregulated in the blood of BC patients with the more aggressive TNBC subtype.Conclusions: Together, these findings establish WAVE3 as a novel marker for increased risk of breast-cancer-specific mortality and for the metastatic potential of the TNBCs, and also identify WAVE3 as an attractive therapeutic target for the treatment of metastatic BC.</p