Improve Cancer Prognosis Research Articles

The TAT-RasGAP317-326 anti-cancer peptide can kill in a caspase-, apoptosis-, and necroptosis-independent manner.

Tumor cell resistance to apoptosis, which is triggered by many anti-tumor therapies, remains a major clinical problem. Therefore, development of more efficient therapies is a priority to improve cancer prognosis. We have previously shown that a cell-permeable peptide derived from the p120 Ras GTPase-activating protein (RasGAP), called TAT-RasGAP317-326, bears anti-malignant activities in vitro and in vivo, such as inhibition of metastatic progression and tumor cell sensitization to cell death induced by various anti-cancer treatments. Recently, we discovered that this RasGAP-derived peptide possesses the ability to directly kill some cancer cells. TAT-RasGAP317-326 can cause cell death in a manner that can be either partially caspase-dependent or fully caspase-independent. Indeed, TAT-RasGAP317-326-induced toxicity was not or only partially prevented when apoptosis was inhibited. Moreover, blocking other forms of cell death, such as necroptosis, parthanatos, pyroptosis and autophagy did not hamper the killing activity of the peptide. The death induced by TAT-RasGAP317-326 can therefore proceed independently from these modes of death. Our finding has potentially interesting clinical relevance because activation of a death pathway that is distinct from apoptosis and necroptosis in tumor cells could lead to the generation of anti-cancer drugs that target pathways not yet considered for cancer treatment.

Combination treatment with flavonoid morin and telomerase inhibitor MST‑312 reduces cancer stem cell traits by targeting STAT3 and telomerase.

Colorectal cancer (CRC) is one of the most commonly diagnosed cancers worldwide. The malignant CRC that undergoes metastasis in the advanced stage is usually refractory to existing chemotherapy and shows a poor prognosis. However, to date, efficient targeted-therapy for metastatic CRC is ill-defined. We tested the hypothesis that combined treatment of flavonoid morin and telomerase inhibitor MST-312 may reduce the cancer stem cell (CSC) traits. To characterize CSC phenotype, we performed the CD133/CD44 subpopulation profiling, tumorsphere formation assay, cell invasion assay and wound healing assay. We have examined the augmenting effects of the combined treatment of morin and MST-312 for 5-FU (5-fluorouracil) efficacy in human colorectal cancer. Morin and MST-312 combined treatment reduced CD133 (+) and CD44 (+) subpopulations in human colorectal and breast cancer cells, respectively. Tumorsphere formation and cell invasiveness were decreased with the morin and MST-312 combination treatment. Consistent with these data, morin and MST-312 treatment decreased the wound healing capacity of human breast cancer cells. Stress and apoptosis antibody arrays revealed that there were specific upregulated and downregulated proteins resulting from different treatments. Phosphorylation levels of BAD, p53 and Chk1 were enhanced upon morin/MST-312 treatments in HT-29 cells, whereas caspase-3 cleavage level and expression of IκBα were down-regulated by combined morin/MST-312 treatment in SW620 cells. Finally, morin and MST-312 co-treatment further augmented the 5-FU efficacy, chemosensitizing the 5-FU resistant human colorectal cancer cells. Taken together, our study suggests that novel targeted-therapy can be implemented by using flavonoid morin and telomerase inhibitor MST-312 for improved cancer prognosis.

Incidence and mortality of gynaecological cancers: Secular trends in urban Shanghai, China over 40 years

AimAppraisal of cancer trends is essential for future cancer control, but relevant studies in China are scarce due to a lack of long-term data. With 40-years of cancer registry data, we sought to evaluate secular time trends in incidence and mortality of gynaecological cancers in an urban Chinese population. Materials and methodsData on incidence and mortality of invasive cervical, uterine and ovarian cancer were collected by the Shanghai Cancer Registry. Age-standardised incidence and mortality rates were calculated for women aged 20–84 in urban Shanghai between 1973 and 2012. Age-period-cohort Poisson regression models were used to evaluate age, period and cohort effects. Overall linear trends, interpreted as the estimated annual percentage change (EAPC), were derived from the net drift in age-drift models. ResultsOverall, cervical cancer incidence and mortality substantially decreased (EAPC = −4.5% and −5.5%, respectively); however, an upward trend was apparent among younger women (age <60). Uterine cancer incidence increased slightly (EAPC = 1.8%), while mortality decreased over time (EAPC = −2.4%). Ovarian cancer incidence and mortality both increased, although the increase in incidence (EAPC = 1.8%) was larger than mortality (EAPC = 0.6%). While cohort effects were most evident for cervical cancer incidence and mortality, significant age, period, and cohort effects were found for all three gynaecological cancers evaluated. ConclusionsThese secular trends in incidence and mortality of gynaecological cancers in Shanghai likely reflect changing risk factor profiles and improved cancer prognosis over time, and suggest new priorities and call for additional efforts for gynaecological cancer prevention and control for women in China.

Cancer Risk and Eicosanoid Production: Interaction between the Protective Effect of Long Chain Omega-3 Polyunsaturated Fatty Acid Intake and Genotype.

Dietary inclusion of fish and fish supplements as a means to improve cancer prognosis and prevent tumour growth is largely controversial. Long chain omega-3 polyunsaturated fatty acids (LCn-3 PUFA), eicosapentaenoic acid and docosahexaenoic acid, may modulate the production of inflammatory eicosanoids, thereby influencing local inflammatory status, which is important in cancer development. Although in vitro studies have demonstrated inhibition of tumour cell growth and proliferation by LCn-3 PUFA, results from human studies have been mainly inconsistent. Genes involved in the desaturation of fatty acids, as well as the genes encoding enzymes responsible for eicosanoid production, are known to be implicated in tumour development. This review discusses the current evidence for an interaction between genetic polymorphisms and dietary LCn-3 PUFA in the risk for breast, prostate and colorectal cancers, in regards to inflammation and eicosanoid synthesis.

Telomere length assessment in leukocytes presents potential diagnostic value in patients with breast cancer.

Telomere shortening is associated with cancer development, primarily through the induction of genomic instability. The majority of studies have indicated that individuals with shorter blood telomeres may be at a higher risk of developing various types of cancer. There is increasing evidence that the study of the alterations in telomere length may improve cancer prognosis. The aim of the present study was to verify the use of telomere length parameters in the diagnostics of breast cancer stage. Telomere length was analyzed in the blood leukocytes of 52 patients with breast cancer relative to 47 control subjects using quantitative polymerase chain reaction. The effects of stage, grade, estrogen receptor, progesterone receptor and human epidermal growth factor 2 (HER2) status were assessed. The current study demonstrated that the average telomeric sequence length was significantly shorter in leukocytes from individuals diagnosed with a more severe stage of breast cancer (T2N1M0) than in leukocytes in the early stages of the disease (T1N0M0) (P=0.0207). Furthermore, the data indicated that telomeres in leukocytes derived from patients with HER2+ breast cancer were significantly longer compared with those with the HER2- type (P=0.0347). These results suggest that the assessment of telomeres in blood leukocytes may, at least partially, correspond with breast cancer staging and HER2 receptor status.

A specific photoimmunotheranostics agent to detect and eliminate skin cancer cells expressing EGFR.

The term "theranostics" represents a new paradigm in medicine especially for cancer treatment. This term was coined by Funkhouser in 2002 and defines a reagent that combines therapeutic and diagnostic properties. It is widely believed that theranostics agents will have considerable impact on healthcare before, during, and after disease by improving cancer prognosis and management simultaneously. Current theranostics approaches still rely on passive tumor targeting strategies, which have scattergun effects and tend to damage both neoplastic and non-neoplastic cells. Here we describe a simple, controlled, and efficient method to generate homogeneous photoimmunotheranostics reagents. This method combines molecular optical imaging, photodynamic therapy, and immunotherapy using SNAP-tag technology. SNAP-tag is a derivative of the O(6)-alkylguanine-DNA alkyltransferase (AGT) which has the ability to efficiently conjugate to O(6)-benzylguanine (BG) molecules under physiological conditions depending on its folding pattern. The theranostics agent was able to specifically recognize various epidermal growth factor receptor (EGFR)-expressing skin cancer cell lines using flow cytometry analysis and confocal microscopy and eliminate them at EC50's of 32-55 nM. These experiments provide a framework for using SNAP-tag technology to generate homogeneous photoimmunotheranostics reagents with unified pharmacokinetic and therapeutic profiles. Furthermore, the reagent generated in this work could be used to simultaneously monitor and suppress the growth of skin squamous carcinoma and melanoma cells expressing EGFR.

Mechanism of Metformin: A Tale of Two Sites

Metformin (dimethylbiguanide) features as a current first-line pharmacological treatment for type 2 diabetes (T2D) in almost all guidelines and recommendations worldwide. It has been known that the antihyperglycemic effect of metformin is mainly due to the inhibition of hepatic glucose output, and therefore, the liver is presumably the primary site of metformin function. However, in this issue of Diabetes Care , Fineman and colleagues (1) demonstrate surprising results from their clinical trials that suggest the primary effect of metformin resides in the human gut. Metformin is an orally administered drug used for lowering blood glucose concentrations in patients with T2D, particularly in those overweight and obese as well as those with normal renal function. Pharmacologically, metformin belongs to the biguanide class of antidiabetes drugs. The history of biguanides can be traced from the use of Galega officinalis (commonly known as galega) for treating diabetes in medieval Europe (2). Guanidine, the active component of galega, is the parent compound used to synthesize the biguanides. Among three main biguanides introduced for diabetes therapy in late 1950s, metformin (Fig. 1 A ) has a superior safety profile and is well tolerated. The other two biguanides, phenformin and buformin, were withdrawn in the early 1970s due to the risk of lactic acidosis and increased cardiac mortality. The incidence of lactic acidosis with metformin at therapeutic doses is rare (less than three cases per 100,000 patient-years) and is not greater than with nonmetformin therapies (3). Major clinical advantages of metformin include specific reduction of hepatic glucose output, with subsequent improvement of peripheral insulin sensitivity, and remarkable cardiovascular safety, but without increasing islet insulin secretion, inducing weight gain, or posing a risk of hypoglycemia. Moreover, metformin has also shown benefits in reducing cancer risk and improving cancer prognosis (4,5), as well as counteracting the cardiovascular complications …

Impact of Treatment Duration on Cervical Cancer Outcomes: Results from a Single Institution

Introduction: Treatment duration has always been related to treatment outcomes in cervical cancer. Our study is aiming to evaluate this parameter and its effect on treatments’ results in patients with locally advanced cervical cancer treated with concurrent chemo radiation. Patients and methods: Between January 2011 and December 2011, all patients diagnosed with cervical cancer and treated with concurrent chemo radiotherapy were retrieved. Treatment duration was calculated from the first day of EBRT to the last day of brachytherapy or EBRT, whichever was last to complete, Fifty-six days (8 weeks) was used as a limit, we analyzed the impact of treatment duration on the overall survival and local control. Results: The median time to complete pelvis RT was 37 days (34-42 days). A median of 15 days (13-26 days) between the last day of Pelvic RT and the start of the first Brachytherapy fraction (Pelvis RT-BT interval) was noted. The median time to complete EBRT in association with BT was55 days (50-69 days) while the median total treatment duration was 61 days (53-71 days). At 3 years the overall survival (OS) rate of the studied cohort was 89.8% and local control (LC) rate was 80.8%. In the univariate analysis, total treatment duration (>56 days) was found to be a significant factor impacting both OS (P=0.014)), and LC (P=0.014). Also in the multivariate analysis, total treatment duration was associated independently with prognosis, and affected both OS (hazard ratio [HR], 2.8; 95% CI, 1.07-7.54, P=0.035) and LC (hazard ratio [HR] 3.2; 95% CI, 1.57-6.64, P=0.001). Conclusion: Extended treatment duration significantly affects treatment outcomes in cervical cancer, efforts should be made to shorten it in a way to improve cancer prognosis.

Anti-VEGF Therapy Induces Proteinuria through Endothelial Disorganization Leading to Nephrin Decrease in Podocytes

Background: VEGF is involved in cancer development by stimulating neo-angiogenesis and tumor proliferation. Anti-angiogenic therapies, especially tyrosine kinase inhibitors such as sunitinib, have significantly improved cancer prognosis. Nevertheless, renal side effects, such as proteinuria and thrombotic microangiopathy, have been reported. The underlying physiopathological mechanisms remain unclear, but animal models and clinical similarities with preeclampsia suggest that such therapies affect the function of the endothelial and epithelial layers of the glomerular basement membrane, with activation of the endothelin signaling system and loss of glomerular slit diaphragm integrity. The aim of this in vitro study was to determine sunitinib effects on normal podocytes and glomerular endothelial cells. Methods: The glomerular microvascular endothelial (GMVEC) and human glomerular visceral epithelial (hGVE) cell lines were incubated with various doses of sunitinib. The MTT Cell Proliferation Assay was used to assess cell proliferation. Expression of nephrin (a major slit diaphragm protein) and endothelin was evaluated by immunofluorescence or western blotting assays. Results: Sunitinib inhibited GMVEC and hGVE cell proliferation in a dose-dependent manner. In GMVEC cells, endothelin transcription and secretion were increased after incubation with sunitinib. Conversely, in hGVE cells, sunitinib did not affect nephrin expression. However, conditioned medium from GMVEC cells incubated with sunitinib modified nephrin expression when added to the culture medium of hVGE cells. This effect was inhibited by pre-incubating hGVE cells with an endothelin inhibitor.

Abstract 629: Label-free isolation of circulating tumor cells for cytomorphological analysis

Abstract INTRODUCTION: The isolation of circulating tumor cells (CTCs) from the bloodstream is a promising tool for improving cancer prognosis, targeted therapies, and to understand the biology of metastatic processes. CTC analysis could benefit from conventional cytology staining procedures and cytopathologist expertise in classifying malignant cells from body fluids, to monitor CTC levels in patients in a low-cost system. However, CTCs are very rare with usually only 1-10 CTCs per mL of blood, which limited their use by cytopathologists in the past. Many current approaches for CTC isolation lead to high backgrounds of non-malignant cells (low purity) and/or capture over large areas, which are difficult to analyze microscopically. METHODS: Vortex is a label-free approach for rare malignant cell enrichment from bodily fluids. This technology requires no prior sample preparation, is cost effective and able to deliver viable and pure cells in a small volume. 21 blood samples were processed through our Vortex device. Larger CTCs are trapped within an array of micro-scale fluid vortices that form in simple rectangular reservoirs, while smaller erythrocytes and leukocytes pass through. The tumor cells are released into a small volume of buffer (&amp;lt; 500uL) and collected directly on a chamber slide for fixation and cytological staining using cytopathology standard operating procedures. After Papanicolaou staining, the slides are examined by cytopathologists. RESULTS: Our CTC collection method was optimized to reduce the loss of rare atypical cells during the cytology procedure (&amp;gt;70% cell recovery), improve the cytological staining quality (defined as good by cytopathologists), with an overall fast workflow (&amp;lt;12H). The collection protocol was designed to be cost-effective, and compatible with commercially available reagents and consumables to facilitate the broad use of our platform by research and clinical labs. Atypical cell populations were isolated by Vortex and identified through conventional Papanicolaou staining in the blood of 15/16 patients with metastatic lung (N = 10) and breast cancer (N = 6). No atypical cells were identified in the blood of 5/5 healthy donors. For 2 lung cancer patients, similar morphological features were seen in the corresponding primary tumors. CONCLUSION: Vortex CTC enrichment is compatible with existing cytology staining and analysis procedures, with significant advantages in terms of processing time, low cost, simplicity, cell integrity and purity. The detection of atypical cells in 15/16 metastatic cancer patient blood samples demonstrates the utility of Vortex enrichment combined with cytological staining as a non-invasive and cost effective method to monitor disease progression and help guide clinical decision-making. Citation Format: Corinne Renier, Edward Pao, Derek E. Go, James Che, Jianyu Rao, Nagesh Rao, Edward Garon, Jonathan Goldman, Rajan P. Kulkarni, Stefanie S. Jeffrey, Elodie Sollier, Dino Di Carlo. Label-free isolation of circulating tumor cells for cytomorphological analysis. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 629. doi:10.1158/1538-7445.AM2015-629

Helping cancer patients quit smoking by increasing their risk perception: a study protocol of a cluster randomized controlled trial.

BackgroundDespite smoking cessation can largely improve cancer prognosis and quality of life, many patients continued smoking after the diagnosis of cancer. This study aims to test the effectiveness of a smoking cessation intervention using risk communication approach to help cancer patients quit smoking, and to improve their health related quality of life.MethodsA cluster randomized controlled trial will be employed. Cancer patients who continued smoking after the diagnosis of cancer and have medical follow-up at the out-patient clinics of the five acute hospitals in Hong Kong will be invited to participate. Subjects in the experimental group will receive (1) health warnings of smoking based on a special designed leaflet; and (2) a patient-centred counseling from nurse counselors with emphasis on risk perceptions of smoking to cancer prognosis. Additionally, they will receive two more telephone counseling at 1-week and 1-month. Control group receive standard care and a generic self-help smoking cessation booklet. Outcomes measure include (a) self-reported and the biochemically validated quit rate, (b) patient’s smoking reduction by at least 50 % compared to baseline, (c) quit attempt(s), (d) change in the intention to quit, (e) change in risk perceptions of smoking, and (f) change in health related quality of life.DiscussionThis study will make an important contribution to evidence-based practice by testing the effectiveness of a tailored smoking cessation intervention for cancer patients. The results will support the development of clinical practice guidelines to promote smoking cessation in cancer patients to improve their prognosis and quality of life.Trial registrationClinicalTrials.gov NCT01685723. Registered 9 November 2012.

Epidemioclinical Feature of Early-Onset Colorectal Cancer at-Risk for Lynch Syndrome in Central Iran

Colorectal cancer (CRC) is becoming one of the most complicated challenges of human health, particularly in developing countries like Iran. In this paper, we try to characterize CRC cases diagnosed < age 50 at-risk for Lynch syndrome within central Iran. We designed a descriptive retrospective study to screen all registered CRC patients within 2000-2013 in Poursina Hakim Research Center (PHRC), a referral gastroenterology clinic in central Iran, based on being early-onset (age at diagnosis ≤50 years) and Amsterdam II criteria. We calculated frequencies and percentages by SPSS 19 software to describe clinical and family history characteristics of patients with early-onset CRC. Overall 1,659 CRC patients were included in our study of which 413 (24.9%) were ≤50 years at diagnosis. Of 219/413 successful calls 67 persons (30.6%) were reported deceased. Family history was positive for 72/219 probands (32.9%) and 53 families (24.2%) were identified as familial colorectal cancer (FCC), with a history of at-least three affected members with any type of cancer in the family, of which 85% fulfilled the Amsterdam II Criteria as hereditary non-polyposis colorectal cancer (HNPCC) families (45/219 or 20.5%). Finally, 14 families were excluded due to proband tumor tissues being unavailable or unwillingness for incorporation. The most common HNPCC-associated extracolonic- cancer among both males and females of the families was stomach, at respectively 31.8 and 32.7 percent. The most common tumor locations among the 31 probands were rectum (32.3%), sigmoid (29.0%), and ascending colon (12.9%). Given the high prevalence of FCC (~1/4 of early-onset Iranian CRC patients), it is necessary to establish a comprehensive cancer genetic counseling and systematic screening program for early detection and to improve cancer prognosis among high risk families.

Integrative genomic and transcriptomic characterization of matched primary and metastatic liver and colorectal carcinoma.

Metastasis is the main cause of cancer mortality but its process remains poorly understood and thus hampers more effective treatment and improved cancer prognosis. To search for metastasis driver genes responsible for tumor spread, we integrated genomic and transcriptomic profiles of 61 matched primary tumors and distant metastases of liver or colorectal carcinoma isolated by laser-capture microdissection and assayed by array-based technologies. We found that primary tumor lesions and their matched distant metastases were largely similar at the genomic and transcriptomic levels, but substantial differences could be found between primary tumors with or without accompanying metastases. Interestingly, metastasis genes were principally tumor type and organ site-specific. Despite distinct pathway enrichment, different metastasis gene sets shared common prognostic capacity and were predictive of hepatocellular carcinoma survival in an independent cohort. Thus, the metastatic propensity is inherent to the primary tumor and the lack of general metastasis genes necessitates the development of specific treatment modalities.

The role of vitamin D in reducing cancer risk and progression

Vitamin D is not really a vitamin but the precursor to the potent steroid hormone calcitriol, which has widespread actions throughout the body. Calcitriol regulates numerous cellular pathways that could have a role in determining cancer risk and prognosis. Although epidemiological and early clinical trials are inconsistent, and randomized control trials in humans do not yet exist to conclusively support a beneficial role for vitamin D, accumulating results from preclinical and some clinical studies strongly suggest that vitamin D deficiency increases the risk of developing cancer and that avoiding deficiency and adding vitamin D supplements might be an economical and safe way to reduce cancer incidence and improve cancer prognosis and outcome.

Biological characterization and analysis of metastasis-related genes in cell lines derived from the primary lesion and lymph node metastasis of a squamous cell carcinoma arising in the mandibular gingiva

Controlling metastatic lesions is an important part of improving cancer prognosis, in addition to controlling the primary lesion. There have been numerous histological studies on primary and metastatic lesions, but little basic research has been performed using cell lines from primary and metastatic lesions belonging to the same patient. In this study, we successfully established a cell line derived from lower gingival carcinoma (WK2) as well as a line derived from secondary cervical lymph node metastasis (WK3F) through primary cultures of tissue from a patient with oral squamous cell carcinoma. We then investigated the biological characteristics of the cancer cell lines from these primary and metastatic lesions and analyzed metastasis-related genes. Comparison of the biological characteristics in vitro showed that WK3F had higher cell proliferation ability and shorter cell doubling time than WK2. WK3F also had increased cell migratory ability and higher invasive and self-replication abilities. Heterotransplantation into nude mice resulted in high tumor formation rates in the tongue and high metastasis rates in the cervical lymph nodes. Changes in WK2 and WK3F gene expression were then comprehensively analyzed using microarrays. Genes with increased expression in WK3F compared to WK2 were extracted when the Z-score was ≥2.0 and the ratio was ≥5.0, while genes with reduced expression in WK3F compared to WK2 were extracted when the Z-score was ≤-2.0 and the ratio was ≤0.2; differences were found in 604 genes. From these, MAGEC1 (88.0-fold), MMP-7 (18.6-fold), SNAI1 (6.6-fold), MACC1 (6.2-fold), and HTRA1 (0.012-fold) were selected as metastasis-related candidate genes. The results suggest that these molecules could be important for clarifying the mechanisms that regulate metastasis and provide new therapeutic targets for inhibiting tumor invasion.

HIC1 Silencing in Triple-Negative Breast Cancer Drives Progression through Misregulation of LCN2

The tumor suppressor gene HIC1 is frequently deleted or epigenetically silenced in human cancer, where its restoration may improve cancer prognosis. Here, we report results illuminating how HIC1 silencing alters effect or signals in triple-negative breast cancer (TNBC), which are crucial for its pathogenesis. HIC1 expression was silenced only in TNBC compared with other molecular subtypes of breast cancer. Restoring HIC1 expression in TNBC cells reduced cell migration, invasion, and metastasis, whereas RNAi-mediated silencing of HIC1 in untransformed human breast cells increased their invasive capabilities. Mechanistic investigations identified the small-secreted protein lipocalin-2 (LCN2), as a critical downstream target of HIC1 in TNBC cells. Elevating LCN2 expression in cells expressing HIC1 partially rescued its suppression of cell invasion and metastasis. Notably, autocrine secretion of LCN2 induced by loss of HIC1 activated the AKT pathway through the neutrophil gelatinase-associated lipocalin receptor, which is associated with TNBC progression. Taken together, our findings revealed that the HIC1-LCN2 axis may serve as a subtype-specific prognostic biomarker, providing an appealing candidate target for TNBC therapy.

Therapeutic effect of β-blockers in triple-negative breast cancer postmenopausal women

Beta-blockers (BB) drugs have been used for decades worldwide, mainly to treat hypertension. However, in recent epidemiological studies, BBs were suggested to improve cancer prognosis. In the wake of this evidence, we evaluated the possible therapeutic effect of BBs in triple-negative breast cancer (TNBC) patients. We identified 800 postmenopausal women operated between 1997 and 2008 for early primary TNBC. The effect of BB intake on the risk of breast cancer (BC) recurrence and death was evaluated through competing risk and Cox regression survival models. At cancer diagnosis, 74 (9.3%) women out of 800 were BBs users. Median age was 62years in BB users and 59years in non-users (P=0.02). BB users and non-users were similarly distributed by all tumor characteristics. The 5-year cumulative incidence of BC-related events was 13.6% in BB users and 27.9% in non-users (P=0.02). The beneficial impact of BBs remained statistically significant at multivariable analysis (HR, 0.52; 95% CI 0.28-0.97), after the adjustment for age, tumor stage, and treatment, peritumoral vascular invasion and use of other antihypertensive drugs, antithrombotics, and statins. Adjusted HRs for metastases and for BC deaths were 0.32 (95% CI 0.12-0.90) and 0.42 (95% CI 0.18-0.97), respectively, in favor of BBs. Hypertension, other antihypertensive drugs, antithrombotics, and statins did not impact prognosis. In this series of postmenopausal TNBC patients, BB intake was associated with a significantly decreased risk of BC-related recurrence, metastasis, and BC death. Innovative therapeutic strategies including BBs should be urgently explored in cancer patients.

PTU-014 Impact of Primary Care Education on the Two Week wait Referral Process for GI Cancers

IntroductionThe two week wait referral process was introduced in 2000 to improve cancer prognosis in the UK with an anticipated 20% reduction in cancer-related deaths. The cancer yield has in...

Mo1113 Impact of Primary Care Education on the Two Week Wait Referral Process for GI Cancers

Introduction The two week wait referral process was introduced in 2000 to improve cancer prognosis in the UK with an anticipated 20% reduction in cancer-related deaths. The cancer yield has in fact been reported as 9–16%. Referrals should be made on the basis of NICE guidance. Previous studies have highlighted that as few as 53% of referrals from Primary Care have been within NICE guidance. The Government’s nine-week “Be clear on cancer” campaign launched in January 2012 via online, TV and radio adverts to increase public awareness of bowel cancer symptoms impacted our service. The proportion of colonoscopies done for the two-week wait service increased from 27% to 48% in the month after the campaign. It is clearly important that referrals made are appropriate to justify this service requirement. This study compares referrals and outcomes before and after a GP education session. Methods Two week wait GI Referrals to the Horton General Hospital between December 2011 and February 2012 were assessed. A presentation was given to Primary Care Practitioners in May highlighting NICE guidance and referrals were re-audited in June 2012. Results 100% of referrals met the two week wait target (to clinic, CT scan or endoscopy) and the mean time to first test was 9 days. The results are summarised below. 24% of Upper GI referrals did not meet NICE guidance, mostly patients referred with anaemia above the referral threshold or for dyspepsia without concerning features. The cancer pick-up was 8.6% (2 oesophageal, 2 gastric and 4 pancreatico-biliary). 26% of Lower GI referrals were non-compliant with guidance (mostly due to rectal bleeding or change in bowel habit shorter than the required time). Cancer pick-up was 5.1%. All but one GI cancer was detected in appropriately referred patients. In June 2012 compliance improved to 81% of upper GI and 79% of lower GI referrals. Reasons for referral outside NICE guidance were similar to the previous cohort. Cancer detection rose to 12.9% for Upper GI and 8.6% for Lower GI cancers. All cancers in the second audit were in appropriately referred patients. Conclusion The study highlights the importance of communication with Primary Care Practitioners who are responsible for referrals for GI cancer exclusion. There have been previous education sessions but despite this there remains an advantage in re-stating the message and keeping regular contact. The cancer detection rate improved with better compliance with NICE guidance and may indicate the value of adhering to this guidance. Larger studies are required to validate this. Disclosure of Interest None Declared

Hashimoto’s Thyroiditis as a Risk Factor of Papillary Thyroid Cancer May Improve Cancer Prognosis

Hashimoto's thyroiditis (HT) has been associated with an elevated risk of papillary thyroid cancer (PTC). To investigate the possible influence of HT on the prognosis of PTC patients, we assessed the related clinical factors linking these conditions, especially serum thyroid-stimulating hormone (TSH) concentration. Case-control study. The First Hospital of China Medical University. The demographic and histological characteristics of 2478 patients who underwent thyroidectomy at our center from 2004 to 2012 were analyzed. Compared with patients with benign thyroid nodular disease, patients with PTC showed a significantly higher prevalence of HT (18.8% vs 7.2%, P < .001), mean TSH concentrations (2.02 ± 1.76 vs 1.46 ± 1.21 mIU/L, P < .001), and positivity rates for anti-thyroglobulin antibodies (TGAB; 40.0% vs 20.4%, P < .001) and anti-thyroid peroxidase antibodies (24.8% vs 12.5%, P < .001). These differences remained after excluding all HT patients. The TSH concentrations were significantly higher in PTC patients with HT than in those without HT (2.54 ± 2.06 vs 1.90 ± 1.66 mIU/L, P = .001). Patients with PTC and HT were younger, with a female predominance, and had smaller sized tumors with less advanced TNM stage compared with those without HT, indicating a better prognosis. Multivariate analysis showed that HT, higher TSH concentration, male sex, and TGAB positivity were independent risk factors for PTC development. Histologically confirmed HT is associated with a significantly higher risk of PTC, due primarily to the higher serum TSH concentrations resulting from the tendency to hypothyroidism in HT. Autoimmunity is another independent risk factor for PTC but may be associated with a better prognosis.