Metformin and other anti-diabetic medication use and breast cancer incidence in the Nurses' Health Studies

We aimed to examine the association between the use of metformin and other anti-diabetic medications and breast cancer incidence within two large prospective cohort studies. We followed 185,181 women who participated in the Nurses' Health Study (NHS; 1994–2016) and the NHSII (1995–2017), with baseline corresponding to the date metformin was approved for type 2 diabetes (T2D) treatment in the US Information on T2D diagnosis, anti-diabetes medications, and other covariates was self-reported at baseline and repeatedly assessed by follow-up questionnaires every 2 years. Breast cancer cases were self-reported and confirmed by medical record review. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between medication use and breast cancer were estimated using Cox proportional hazards regression models, adjusting for breast cancer risk factors. During 3,324,881 person-years of follow-up, we ascertained 9,192 incident invasive breast cancer cases, of which 451 were among women with T2D. Compared with women without T2D (n = 169,263), neither metformin use (HR = 0.97; 95% CI = 0.81–1.15) nor other anti-diabetic medications use (HR = 1.11; 95% CI = 0.90–1.36) associated with significantly lower breast cancer incidence. Among women with T2D (n = 15,918), compared with metformin never users, metformin ever use was not significantly inversely associated with breast cancer (HR = 0.92; 95% CI = 0.74–1.15). Although we observed that past use of metformin was inversely associated with breast cancer in the T2D population (HR = 0.67; 95% CI = 0.48–0.94), current use (HR = 1.01; 95% CI = 0.80–1.27) and longer duration of metformin use were not associated with breast cancer (each 2-year interval: HR = 1.01; 95% CI = 0.95–1.07). Overall, metformin use was not associated with the risk of developing breast cancer among the overall cohort population or among women with T2D.     

Concurrent use of tamoxifen with CYP2D6 inhibitors and the risk of breast cancer recurrence

Concurrent use of tamoxifen and cytochrome P450 2D6 (CYP2D6) inhibitors, such as selective serotonin reuptake inhibitors, has been shown to decrease plasma concentrations of tamoxifen metabolites. However, it is still unclear whether such concurrent use affects tamoxifen’s effectiveness. Thus, the objective of this study is to determine whether concurrent use of tamoxifen with CYP2D6 inhibitors increases the risk of recurrence in patients newly diagnosed with breast cancer. We conducted a nested case–control analysis within a population-based cohort from the UK General Practice Research Database. The cohort included women with a first-ever diagnosis of breast cancer who were prescribed tamoxifen between January 1, 1998 and June 30, 2008. Cases consisted of all patients with a breast cancer recurrence occurring during follow-up. Up to ten controls were matched to each case on year of birth, date of cohort entry, and duration of follow-up. Conditional logistic regression was used to estimate rate ratios (RR) of breast cancer recurrence in patients who concurrently used tamoxifen with CYP2D6 inhibitors, compared to patients who only used tamoxifen. The cohort included 9,209 incident users of tamoxifen, of whom 807 were diagnosed with a breast cancer recurrence. Concurrent use was not associated with an increased incidence of breast cancer recurrence (adjusted RR 1.07, 95% 0.88, 1.30). Type and strength of CYP2D6 inhibitors, as well as duration of concurrent use did not affect breast cancer recurrence. These results remained consistent after performing sensitivity analyses. The results of this large population-based study indicate that concurrent use of tamoxifen with CYP2D6 inhibitors does not increase the risk of recurrence.     

Metformin May Improve the Prognosis of Patients with Pancreatic Cancer

Background: Pancreatic cancer risk is increased in patients with type 2 diabetes, while being reduced bymetformin treatment. However, it is unclear whether metformin could be associated with clinical outcomes ofpatients with pancreatic cancer and concurrent type 2 diabetes. Materials and Methods: A pooled analysis of4 publications including 1,429 patients was performed to investigate the association of metformin and overallsurvival(OS) in patients with pancreatic cancer and concurrent type 2 diabetes. Results: A borderline significantrelative survival benefit was found in metformin treated patients compared with non-metformin treated patients(hazard ratio 0.80; 95% CI: 0.62-1.03). Conclusions: These results suggest that further investigation is warrantedof whether metformin may benefit the survival of patients with pancreatic cancer and concurrent type 2 diabetes.     

Diabetes,metformin and cancer risk in myotonic dystrophy type I

Myotonic dystrophy type I (DM1) is an autosomal dominant multisystem disorder characterized by myotonia and muscle weakness. Type 2 diabetes (T2D) and cancer have been shown to be part of the DM1 phenotype. Metformin, a well-established agent for the management of T2D, is thought to have cancer-preventive effects in the general population. In our study, we aimed to assess the association between T2D, metformin use and the risk of cancer in DM1 patients. We identified a cohort of 913 DM1 patients and an age-, sex- and clinic-matched cohort of 12,318 DM1-free controls from the UK Clinical Practice Research Datalink, a large primary care records database. We used Cox regression models to assess cancer risk in T2D patients who were metformin users or nonusers compared to patients without T2D. Separate analyses were conducted for DM1 patients and controls. T2D was more prevalent in DM1 than in controls (8% vs. 3%, p < 0.0001). DM1 patients with T2D, compared to those without T2D, were more likely to develop cancer (hazard ratio [HR] = 3.60, 95% confidence interval [CI] = 1.18–10.97; p = 0.02), but not if they were treated with metformin (HR = 0.43, 95% CI = 0.06–3.35; p = 0.42). Among controls, we observed no significant associations between T2D and cancer risk in either users or nonusers of Metformin (HR = 1.28, 95% CI = 0.91–1.79; p = 0.16 and HR = 1.13, 95% CI = 0.72–1.79; p = 0.59, respectively). These results show an association between T2D and cancer risk in DM1 patients and may provide new insights into the possible benefits of Metformin use in DM1.     

The risk of prostate cancer for men on aspirin,statin or antidiabetic medications

BackgroundA decreased risk of prostate cancer (PCa) has been suggested in men taking aspirin, statins and metformin, although the evidence has been conflicting. We estimated the association between prescribed medications, prostate specific antigen (PSA) levels and the risk of either any PCa or high-grade PCa.MethodsThis population-based cohort study included 185,667 men having a first recorded PSA test and 18,574 men having a first prostate biopsy in Stockholm County, Sweden for the period 2007–2012. Detailed clinical information including PSA levels, biopsy results, comorbidities and educational level were obtained from population-based registers. High-grade prostate cancer was defined as a Gleason score of seven or higher. Differences in PSA levels by medication status were estimated using linear regression on log PSA values. PCa risk was estimated using multivariate logistic regression.ResultsCompared with men who were not on medication, the PSA level at the first PSA test was lower among men using 75 mg/dose aspirin (−3.9% change in PSA concentration; 95% confidence interval (CI): −5.8 to −2.1), statin (−4.6%; 95% CI: −6.2 to −2.9), metformin (−14%; 95% CI: −17 to −12) and insulin (−16%; 95% CI: −18 to −14). Men using any statins had an increased risk of both high-grade PCa (odds ratio (OR) 1.25; 95% CI: 1.10–1.42) and PCa of any grade (OR 1.16; 95% CI 1.04–1.29). There were no significant associations between aspirin or any antidiabetic medication and the risk of PCa.ConclusionWe found no protective effect of aspirin, statins or antidiabetics in terms of risk for any PCa or high-grade PCa. Use of any statins was associated with an elevated risk of being diagnosed with high-grade prostate cancer.     

Metformin Is Associated With Survival Benefit in Cancer Patients With Concurrent Type 2 Diabetes: A Systematic Review and Meta‐Analysis

Purpose.

Patients with type 2 diabetes have increased cancer risk and cancer-related mortality, which can be reduced by metformin treatment. However, it is unclear whether metformin can also modulate clinical outcomes in patients with cancer and concurrent type 2 diabetes.

Patients and Methods.

A meta-analysis of 20 publications that included 13,008 subjects was performed to investigate the association between metformin and overall survival (OS) as well as cancer-specific survival (CSS) in patients with cancer and concurrent type 2 diabetes.

Results.

We found that there was a relative survival benefit associated with metformin treatment compared with treatment with other glucose-lowering medications in both OS and CSS (hazard ratio [HR] = 0.66; 95% confidence interval [CI]: 0.55–0.79 and HR = 0.62; 95% CI: 0.46–0.84, respectively). These associations were also observed in subgroups by cancer type and country.

Conclusion.

These results suggest that metformin is the drug of choice in the treatment of patients with cancer and concurrent type 2 diabetes.     

Can transanal endoscopic microsurgery effectively treat T1 or T2 rectal cancer?A systematic review and meta-analysis

AimWe aimed to compare the safety and oncological outcomes of transanal endoscopic microsurgery (TEM) and radical surgery (RS) for patients with T1 or T2 rectal cancer.MethodWe searched Pubmed, Embase, Cochrane Library databases for relevant studies comparing TEM with RS in rectal cancer published until April 2020. We focused on safety and oncological outcomes.ResultsThis meta-analysis included 3526 patients from 12 studies. Compared with RS, TEM had a shorter operative time (weighted mean difference [WMD] −110.02, 95% confidence interval [CI]: 143.98, −76.06), less intraoperative blood loss (WMD -493.63, 95% CI: 772.66, −214.59), lower perioperative morality (risk ratio [RR] 0.25, 95% CI: 0.06, 0.99), and fewer postoperative surgical complications (RR 0.23, 95% CI: 0.11,0.45). TEM was associated with more patients with a positive margin or a doubtfully complete margin than RS (RR 7.36, 95% CI: 3.66, 14.78). TEM was associated with higher local recurrence (RR 2.63, 95% CI: 1.60, 4.31) and overall recurrence (RR 1.60, 95% CI: 1.09, 2.36). TEM had a negative effect on 5-year overall survival (hazard ratio [HR] 1.51, 95% CI: 1.16, 1.96), especially in the T2 without neoadjuvant therapy (NAT) subgroup (HR 2.02, 95% CI: 1.32, 3.09), but in the subgroups of T1 or T2 with NAT before TEM, TEM did not yield a significantly lower overall survival than RS.ConclusionTEM seems appropriate for T1 rectal cancer with favourable histopathology. For patients with T2 rectal cancer, NAT before TEM may contribute to achieving oncological outcomes equivalent to that achieved with RS.     

The rs1050450 C > T polymorphism of GPX1 is associated with the risk of bladder but not prostate cancer: evidence from a meta-analysis

Glutathione peroxidase (GPX) is an endogenous antioxidant enzyme counteracting oxidative stress. Accumulating evidence has demonstrated that the GPX1 rs1050450 C?>?T polymorphism may modulate cancer risk, but the association of GPX1 rs1050450 polymorphism with bladder cancer (BC) and prostate cancer (PCa) is still inconclusive. This meta-analysis was designed to determine the exact association of GPX1 rs1050450 C?>?T polymorphism with the risk of bladder cancer and prostate cancer. Odds ratios (ORs) and 95 % confidence intervals (CI) were calculated to estimate the association strength. Databases of PubMed, EMBASE, and China National Knowledge Infrastructure were searched to retrieve eligible studies. In total, ten eligible studies with 6,194 participants were included. By pooling all eligible studies, we found that carriers of the variant T allele were associated with a significantly increased risk of urinary tract cancer (T vs. C: OR?=?1.459 and 95 % CI, 1.086–1.962; CT/TT vs. CC: OR?=?1.411 and 95 % CI, 1.053–1.891). In stratified analysis, we observed that the rs1050450 C?>?T polymorphism was significantly associated with an increased risk of BC (T vs. C: OR?=?2.111 and 95 % CI, 1.020–4.368; CT/TT vs. CC: OR?=?1.876 and 95 % CI, 1.011–3.480), while the association was not significant for PCa. Egger’s test and Begg’s test revealed no publication bias. The present meta-analysis provides evidence that the GPX1 rs1050450 C?>?T polymorphism leads to an increased risk of BC but not the risk of PCa.     

Can We Improve the Preoperative Prediction of Prostate Cancer Recurrence With Multiparametric MRI?

IntroductionThe use of multiparametric magnetic resonance imaging (mpMRI) to assess prostate cancer (PCa) has increased over the past decade. We aimed to assess if preoperative mpMRI lesion score, a variable routinely available for men undergoing pre-biopsy MRI, improves the performance of commonly used preoperative predictive models for PCa recurrence.Patients and MethodsWe analyzed data from 372 patients with PCa treated with radical prostatectomy in 2012 to 2017 and assessed with pre-biopsy mpMRI within 6 months prior to surgery. Suspicious areas for cancer were scored on a standardized 5-point scale. Cox regression was used to assess the association between mpMRI score and the risk of postoperative biochemical recurrence. Two different models were tested accounting for factors included in the Kattan nomogram and in the D’Amico risk-classification.ResultsOverall, 53% and 30% of patients were found with a lesion scored 4 or 5 at pre-biopsy mpMRI, respectively. Risk varied widely by mpMRI (29% 2-year risk of biochemical recurrence for a score of 5 vs. 5% for a score of 1-2), and mpMRI score was associated with large hazard ratios after adjusting for stage, grade, and prostate-specific antigen: 1.66, 1.96, and 2.71 for scores 3, 4, and 5, respectively. However, 95% confidence intervals were very wide (0.19-14.20, 0.26-14.65, and 0.36-20.55, respectively) and included 1.ConclusionsOur data did not show that preoperative models, commonly used to assess PCa risk, were improved after including the pre-biopsy mpMRI score. However, the value of pre-biopsy mpMRI to improve preoperative risk models should be investigated in larger data sets.     

Effect of metformin on survival outcomes in diabetic patients with triple receptor-negative breast cancer

BACKGROUND:

Recent observational studies have shown that metformin use in diabetic patients decreases both cancer incidence and mortality. Metformin use is also independently predictive of pathologic complete response. In the current study, the authors explored the association between metformin use and survival outcomes in patients with triple receptor‐negative breast cancer (TNBC) who were receiving adjuvant chemotherapy.

METHODS:

The Breast Cancer Management System database of The University of Texas MD Anderson Cancer Center identified 1448 women who received adjuvant chemotherapy for TNBC between 1995 and 2007. Patients were categorized by diabetes status and metformin use. The Kaplan‐Meier product‐limit method was used to calculate distant metastasis‐free survival (DMFS), recurrence‐free survival (RFS), and overall survival (OS). Cox proportional hazards models were fit to determine the association between metformin use and survival outcomes.

RESULTS:

The study cohort was comprised of 63 diabetic patients receiving treatment with metformin, 67 diabetic patients not receiving metformin, and 1318 nondiabetic patients. Patients in the diabetic groups tended to be older (P = .005); more diabetic patients were postmenopausal (P = .0007), black (P = .0001), and obese (P < .0001). At a median follow‐up of 62 months, there were no significant differences with regard to 5‐year DMFS (P = .23), RFS (P = .38), and OS (P = .58) between the 3 groups. Compared with the metformin group, patients who did not receive metformin (hazard ratio [HR], 1.63; 95% confidence interval [95% CI], 0.87‐3.06 [P = .13]) and nondiabetic patients (HR, 1.62; 95% CI, 0.97‐2.71 [P = .06]) tended to have a higher risk of distant metastases.

CONCLUSIONS:

The findings of the current study suggest that metformin use during adjuvant chemotherapy does not significantly impact survival outcomes in diabetic patients with TNBC. Cancer 2012;. © 2011 American Cancer Society.     

The effects of metformin on the survival of colorectal cancer patients with diabetes mellitus

Metformin use has been associated with decreased cancer risk and mortality. However, the effects of metformin on clinical outcomes of colorectal cancer (CRC) are not defined. This study aimed to evaluate the association between metformin use and mortality of CRC in diabetic patients. We identified 595 patients who were diagnosed both CRC and diabetes mellitus. Patients were compared by two groups; 258 diabetic patients taking metformin and 337 diabetic patients not taking metformin. Patient's demographics, clinical characteristics, overall mortality and CRC-specific mortality were analyzed. After a median follow-up of 41 months, there were 71 total deaths (27.5%) and 55 CRC-specific deaths (21.3%) among 258 patients who used metformin, compared with 136 total deaths (40.4%) and 104 CRC-specific deaths (30.9%) among 337 patients who did not use metformin. Metformin use was associated with decreased overall mortality (p = 0.018) and CRC-specific mortality (p = 0.042) by univariate analysis. After adjustment for clinically relevant factors, metformin use showed lower risk of overall mortality (HR, 0.66; 95% CI 0.476-0.923; p = 0.015) and CRC-specific mortality (HR, 0.66; 95% CI 0.45-0.975; p = 0.037) in CRC patients with diabetes. Metformin use in CRC patients with diabetes is associated with lower risk of CRC-specific and overall mortality.     

Impact of Concomitant Medications on Biochemical Outcome in Localised Prostate Cancer Treated with Radiotherapy and Androgen Deprivation Therapy

AimsSeveral classes of concomitant medications have been shown to affect oncological outcomes in patients with prostate cancer (PCa). We assessed the association between the use of commonly prescribed concomitant medications and biochemical relapse-free survival (bRFS) in patients with localised PCa treated with radiotherapy and androgen deprivation therapy (ADT).Materials and methodsA secondary pooled analysis of two phase III randomised trials was carried out. In the first trial, patients with localised PCa with clinical stage T1b-T3, prostate-specific antigen <30 ng/ml and Gleason score ≤7 were treated with radical radiotherapy and 6 months of ADT starting 4 months before or concomitantly with radiotherapy. In the second trial, patients with high-risk PCa were treated with radical radiotherapy and 36 months of ADT with randomisation to three-dimensional conformal or intensity-modulated radiotherapy. Information on concomitant medications was collected from the medical record. Univariable and multivariable Cox regression was used to identify factors associated with bRFS.ResultsOverall, 486 patients were evaluable. The median follow-up was 125 months; 10-year bRFS was 83.7%. On univariable analysis, receipt of metformin was significantly associated with worse bRFS. Ten-year bRFS was 73% and 85% for patients with and without concomitant metformin (adjusted hazard ratio 2.11, 95% confidence interval 1.03–4.33). Similar evidence of an association was observed with sulfonamide-based α1-receptor blockers (adjusted hazard ratio 2.72, 95% confidence interval 1.31–5.66). However, no such association was seen with receipt of quinazoline-based α1-receptor blockers (adjusted hazard ratio 1.09, 95% confidence interval 0.42–2.82). There was no significant association between bRFS and receipt of all other medication classes considered.ConclusionsIn this population of patients with localised PCa treated with radiotherapy and ADT, receipt of concomitant metformin and sulfonamide-based α1-receptor blockers was associated with inferior biochemical outcome. Randomised trials are required to assess the true effect of these medications on oncological outcomes in localised PCa.     

Metformin increases survival in hormone receptor-positive,HER2-positive breast cancer patients with diabetes

Introduction

Metformin use has recently been observed to decrease both the rate and mortality of breast cancer. Our study was aim to determine whether metformin use is associated with survival in diabetic breast cancer patients by breast cancer subtype and systemic treatment.

Methods

Data from the Asan Medical Center Breast Cancer Database from 1997 to 2007 were analyzed. The study cohort comprised 6,967 nondiabetic patients, 202 diabetic patients treated with metformin, and 184 diabetic patients that did not receive metformin. Patients who were divided into three groups by diabetes status and metformin use were also divided into four subgroups by hormone receptor and HER2-neu status.

Results

In Kaplan-Meier analysis, the metformin group had a significantly better overall and cancer specific survival outcome compared with non metformin diabetic group (P <0.005 for both). There was no difference in survival between the nondiabetic and metformin groups. In multivariate analysis, Compared with metformin group, patients who did not receive metformin tended to have a higher risk of metastasis with HR 5.37 (95 % CI, 1.88 to 15.28) and breast cancer death with HR 6.51 (95 % CI, 1.88 to 15.28) on the hormone receptor-positive and HER2-negative breast cancer. The significant survival benefit of metformin observed in diabetic patients who received chemotherapy and endocrine therapy (HR for disease free survival 2.14; 95 % CI 1.14 to 4.04) was not seen in diabetic patients who did not receive these treatments.

Conclusion

Patients receiving metformin treatment when breast cancer diagnosis show a better prognosis only if they have hormone receptor-positive, HER2-positive tumors. Metformin treatment might provide a survival benefit when added to systemic therapy in diabetic patients.     

Impact of Caspase-8 (CASP8) -652 6N Del and D302H Polymorphisms on Prostate Cancer in Different Ethnic Groups

Background: Despite evidence suggesting roles for caspase-8 (CASP8) -652 6N del and D302H polymorphismsin prostate cancer (PCa), the association of these polymorphisms with PCa risk remains inconclusive. Therefore,a meta-analysis was performed to more precisely estimate the association of CASP8 -652 6N del and D302Hpolymorphisms with PCa susceptibility. Materials and Methods: A comprehensive literature search was conductedto identify all case-control studies of CASP8 D302H and -652 6N del polymorphisms and PCa risk. Odds ratios(ORs) and 95% confidence intervals (CIs) were used to assess the strength of the association and the precision ofthe estimate, respectively. Results: Nine -625 6N del studies and 4 D302H studies were included. CASP8 -652 6Ndel and D302H polymorphisms were not significantly associated with PCa risk in the overall analyses. However,in the subgroup analysis stratified by ethnicity, -625 6N del was significantly associated with PCa risk in theEast Asian and Indian populations under the recessive model. Furthermore, the subgroup analysis stronglysuggested that D302H was associated with lower PCa risk in the Non-Indian population under the dominantmodel. Conclusions: In our meta-analysis, ethnic-specific differences were evident in the association of CASP8-625 6N del and D302H polymorphisms with PCa risk.     

Impact of concurrent versus sequential tamoxifen with radiation therapy in early-stage breast cancer patients undergoing breast conservation treatment.

PURPOSE: To assess the impact of sequencing of tamoxifen and radiation therapy (RT) on outcomes in early-stage breast cancer. PATIENTS AND METHODS: This retrospective study evaluates the effect of the sequence of tamoxifen with RT on outcomes in stage I to II breast cancer patients who underwent breast-conservation treatment (BCT) and received adjuvant tamoxifen, with or without adjuvant chemotherapy. Patients were grouped as concurrent (tamoxifen given during RT followed by continued tamoxifen; 174 patients) and sequential (RT followed by tamoxifen; 104 patients). RESULTS: Median follow-up after RT was 8.6 years for both groups. The pathologic T and N stage, race, estrogen and progesterone status, number of positive nodes, and RT were comparable between the two groups (all P >/= .08). More women age 49 years or younger and women who received chemotherapy were in the sequential group than the concurrent group (6% and 25%, respectively; P < .0001). The sequence of tamoxifen therapy did not influence 10-year local recurrence rates (sequential, 7%; concurrent, 3%; P = .52), overall survival (sequential, 86%; concurrent, 81%; P = .64), or relapse-free survival (sequential, 76%; concurrent, 85%; P = .35). When adjusting age and chemotherapy use in the multivariable Cox model, hazard ratios comparing sequential versus concurrent tamoxifen therapy were 1.56 (95% CI, 0.87 to 2.79), 1.23 (95% CI, 0.63 to 2.41), and 1.22 (95% CI, 0.33 to 4.49) for the overall survival, relapse-free survival, and local recurrence, respectively. CONCLUSION: The therapeutic regimens of tamoxifen given concurrently or sequentially with RT both appear to be reasonable options for patients treated with BCT.     

Serum inflammatory markers in relation to prostate cancer severity and death in the Swedish AMORIS study

Inflammation is a well‐documented driver of cancer development and progression. However, little is known about its role in prostate carcinogenesis. Thus, we examined the association of C‐reactive protein (CRP), haptoglobin, albumin and white blood cells (WBC) with prostate cancer (PCa) severity (defined by PCa risk category and clinicopathological characteristics) and progression (defined by PCa death). We selected 8,471 Swedish men with newly diagnosed PCa who had exposure measurements taken approximately 14 years prior to diagnosis. We calculated odds ratio (OR) and 95% confidence interval (CI) for the associations between the inflammatory markers and PCa severity using logistic regression, while Cox proportional hazard regression was used for the associations with overall and PCa death. Serum CRP levels were associated with increased odds of high risk and metastatic PCa, and high PSA levels (≥20 µg/L) (OR: 1.29; 95% CI: 1.06–1.56, 1.32; 1.05–1.65 and 1.51; 1.26–1.81, respectively). Similarly, higher haptoglobin levels were associated with increased odds of metastatic PCa, high PSA level and possibly high grade PCa (1.38; 1.10–1.74, 1.50; 1.17–1.93 and 1.25; 1.00–1.56, respectively). Albumin was positively associated with Gleason 4 + 3 tumour (1.38; 1.02–1.86) and overall death (HR_{unit increase in log}: 1.60; 95% CI: 1.11–2.30), but inversely associated with high risk PCa and high PSA levels (≥20 µg/L) (0.71; 0.56–0.89 and 0.72; 0.5 9–0.90). WBC was associated with increased odds of T3–T4 PCa. Except for albumin, none of these markers were associated with PCa death or overall death. Systemic inflammation as early as 14 years prior to diagnosis may influence prostate cancer severity.     

Impact of hospital procedure volume on surgical operation and long-term outcomes in high-risk curatively resected rectal cancer: findings from the Intergroup 0114 Study.

PURPOSE: Prior studies have demonstrated superior outcomes after a curative surgical resection of rectal cancer at hospitals where the volume of such surgeries is high. However, because these studies often lack detailed information on tumor and treatment characteristics as well as cancer recurrence, the true nature of this relation remains uncertain. PATIENTS AND METHODS: We studied a nested cohort of 1,330 patients with stage II and stage III rectal cancer participating in a multicenter, adjuvant chemoradiotherapy trial. We analyzed differences in rates of sphincter-preserving operations, overall survival, and cancer recurrence by hospital surgical volume. RESULTS: We observed a significant difference in the rates of abdominoperineal resections across tertiles of hospital procedure volume (46.3% for patients resected at low-volume, 41.3% at medium-volume, and 31.8% at high-volume hospitals; P <.0001), even after adjustment for tumor distance from the anal verge. However, this higher rate of sphincter-sparing operations at high-volume centers was not accompanied by any increase in recurrence rates. Hospital surgical volume did not predict overall, disease-free, recurrence-free, or local recurrence-free survival. However, among patients who did not complete the planned adjuvant chemoradiotherapy (270 patients), those who underwent surgery at low-volume hospitals had a significant increase in cancer recurrence (adjusted hazard ratio, 1.94; 95% CI, 1.01 to 3.72; P =.04 for the trend) and a nonsignificant trend toward increased overall mortality (P =.08) and local recurrence (P =.10). In contrast, no significant volume-outcome relation was noted among patients who did complete postoperative therapy. CONCLUSION: Using prospectively recorded data, we found that hospital surgical volume had no significant effect on rectal cancer recurrence or survival when patients completed standard adjuvant therapy. Sphincter-preserving surgery was more commonly performed at high-volume centers.     

Metformin use and prostate cancer in Caucasian men: results from a population-based case–control study

Purpose  

Metformin is a commonly used medication for type II diabetes mellitus. Epidemiologic studies have suggested a decreased relative risk of cancer with metformin use, and preclinical studies of prostate cancer (PCa) have shown antitumor activity with metformin. In this study, we explore the relationship between metformin use and PCa risk in a population-based case–control study.     

Therapeutic Use of Metformin in Diabetes and Survival Outcomes in Endometrial Cancer Patients with Diabetes

Objectives: To compare survival outcomes between endometrial cancer (EC) patients with diabetes who usedmetformin to those who did not use metformin. Materials and Methods: A retrospective cohort study was conductedof EC patients who were diabetes at the time of their cancer diagnosis and had been scheduled for elective surgeryat Rajavithi Hospital between 1 January 2003 and 31 December 2013. The patients were excluded if they had typeI diabetes mellitus and a history of other cancers. Results: Of 1,262 EC patients in the study period, there was 212(16.8%) patients who met the inclusion criteria. Among them, 90 (42.5%) were non-metformin users and 122 (57.5%)were metformin users. With a median follow-up of 47 months, the 5-year overall survivals (76.4% vs 77.9%, p=0.959)and the 5-year progression-free survivals (92.6% vs 84.7%, p=0.091) did not significantly differ between the bothgroups. On Cox proportional-hazards regression analysis, independent prognostic factors for overall survival (OS)were FIGO stage, depth of myometrial invasion, and cervical involvement. Patients with non-endometrioid histologyand advanced stage were found to have a significant effect on progression-free survival (PFS). However, metforminused did not predict either OS (HR, 0.99; 95%CI, 0.56-1.73; p=0.959) or PFS (HR, 2.19; 95%CI, 0.86-5.55; p=0.099).Conclusion: Overall, a significant effect of metformin on survival outcomes in EC patients with diabetes was not foundin the current study. Larger studies with a prospective randomized control design are needed to clarify the benefit ofmetformin as a strategy for endometrial cancer prevention and treatment.