Use of 5-alpha reductase inhibitors and risk of gastrointestinal cancers in men with benign prostatic hyperplasia: A population-based cohort study.

Pre-clinical evidence suggests that 5-alpha reductase inhibitors (5ARi's), prescribed in the treatment of benign prostatic hyperplasia, reduce colorectal and gastro-oesophageal cancer incidence via action on the male hormonal pathway. However, few studies to date have investigated this association at the population level. Our study aimed to investigate the risk of colorectal and gastro-oesophageal cancers with the use of 5ARi's. We conducted a retrospective cohort study of new users of 5ARi's and alpha-blockers among patients with benign prostatic hyperplasia in the UK Clinical Practice Research Datalink. Patients were followed until a first ever diagnosis of colorectal or gastro-oesophageal cancer, death from any cause or end of registration with the general practice or 31st of December 2017. Cox proportional hazards models with inverse probability of treatment weights were used to calculate weighted hazard ratios (HR) and 95% confidence intervals (CIs) of incident colorectal cancer or gastro-oesophageal cancer associated with the use of 5ARi's compared to alpha-blockers. During a mean follow-up of 6.6 years, we found no association between the use of 5ARi's and colorectal (HR: 1.13, 95% CI 0.91-1.41) or gastro-oesophageal (HR 1.14, 95% CI 0.76-1.63) cancer risk compared to alpha-blockers. Sensitivity analysis showed largely consistent results when varying lag periods, using multiple imputations, and accounting for competing risk of death. Our study found no association between the use of 5ARi's and risk of colorectal or gastro-oesophageal cancer in men with benign prostatic hyperplasia.

Hormone replacement therapy and cancer mortality in women with 17 site-specific cancers: a cohort study using linked medical records.

BACKGROUND: There is limited evidence on the safety of Hormone Replacement Therapy (HRT) in women with cancer. Therefore, we systematically examined HRT use and cancer-specific mortality in women with 17 site-specific cancers. METHODS: Women newly diagnosed with 17 site-specific cancers from 1998 to 2019, were identified from general practitioner (GP) records, hospital diagnoses or cancer registries in Scotland, Wales and England. Breast cancer patients were excluded because HRT is contraindicated in breast cancer patients. The primary outcome was time to cancer-specific mortality. Time-dependent Cox regression models were used to calculate adjusted hazard ratios (HR) and 95% confidence intervals (95% CIs) for cancer-specific mortality by systemic HRT use. RESULTS: The combined cancer cohorts contained 182,589 women across 17 cancer sites. Overall 7% of patients used systemic HRT after their cancer diagnosis. There was no evidence that HRT users, compared with non-users, had higher cancer-specific mortality at any cancer site. In particular, no increase was observed in common cancers including lung (adjusted HR = 0.98 95% CI 0.90, 1.07), colorectal (adjusted HR = 0.79 95% CI 0.70, 0.90), and melanoma (adjusted HR = 0.77 95% CI 0.58, 1.02). CONCLUSIONS: We observed no evidence of increased cancer-specific mortality in women with a range of cancers (excluding breast) receiving HRT.

Antiplatelet drugs and breast cancer risk in a large nationwide Danish case-control study.

Low-dose aspirin has been hypothesized to prevent cancer risk by inhibiting platelet aggregation. However, the anti-cancer effect of low-dose aspirin has recently been questioned and its effect on breast cancer development remains unclear. The impact of other antiplatelet drugs on breast cancer risk has rarely been evaluated. Thus, this study aimed to investigate the associations between breast cancer risk and antiplatelet drug use in a nationwide nested case-control study. From the Danish healthcare registries, we identified as cases all women with invasive breast cancer diagnosis between 2001 and 2018 (n = 68 852). The date of diagnosis corresponded to the index date. We matched cases to 10 population controls on age and calendar time, using risk set sampling. Controls were assigned the same index date as their matched case. We used the prescription registry to identify exposure to low-dose aspirin, clopidogrel and dipyridamole. We defined ever use of antiplatelet drugs as at least two prescriptions filled up to 1 year before the index date. We applied conditional logistic regression to calculate odds ratios (ORs) and 95% confidence intervals for breast cancer associated with the use of antiplatelet drugs, overall, by breast cancer subtype and by cumulative dose. Twelve percent of women had ever been exposed to low-dose aspirin, 2% to clopidogrel and 2% to dipyridamole. In multivariable models, breast cancer risk was not associated with ever use of low-dose aspirin (OR = 1.00 [0.97-1.03]), clopidogrel (OR = 0.93 [0.87-1.00]), and dipyridamole (OR = 1.02 [0.94-1.10]), compared with never use, and there was no evidence of a dose-response relation. However, we found an inverse association between dipyridamole use and breast cancer risk among women aged <55 years old, with suggestion of a dose-response relationship (OR per 1000 Defined Daily Doses = 0.72 [0.54-0.95]). Associations did not differ by breast cancer histological type, estrogen receptor status or clinical stage at diagnosis. Overall, the findings from this study do not support the use of antiplatelet drugs for breast cancer prevention.

Exposure to Ranitidine and Risk of Bladder Cancer: A Nested Case-Control Study.

INTRODUCTION: Ranitidine has been shown to contain the carcinogen N-nitrosodimethylamine and increase urinary N-nitrosodimethylamine in humans. We investigated whether ranitidine use is associated with increased bladder cancer risk. METHODS: A nested case-control study was conducted within the Primary Care Clinical Informatics Unit Research database which contains general practice records from Scotland. Bladder cancer cases, diagnosed between 1999 and 2011, were identified and matched with up to 5 controls (based on age, sex, general practice, and date of registration). Ranitidine, other histamine-2 receptor agonists, and proton pump inhibitors were identified from prescribing records. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression after adjusting for comorbidities and smoking. RESULTS: There were 3,260 cases and 14,037 controls. There was evidence of an increased risk of bladder cancer in ranitidine users, compared with nonusers (fully adjusted OR = 1.22; 95% CI 1.06-1.40), which was more marked with use for over 3 years of ranitidine (fully adjusted OR = 1.43; 95% CI 1.05-1.94). By contrast, there was little evidence of any association between proton pump inhibitor use and bladder cancer risk based on any use (fully adjusted OR = 0.98; 95% CI 0.88-1.11) or over 3 years of use (fully adjusted OR = 0.98; 95% CI 0.80-1.20). DISCUSSION: In this large population-based study, the use of ranitidine particularly long-term use was associated with an increased risk of bladder cancer. Further studies are necessary to attempt to replicate this finding in other settings.

Hormone replacement therapy in women with cancer and risk of cancer-specific mortality and cardiovascular disease: a protocol for a cohort study from Scotland and Wales.

BACKGROUND: Hormone replacement therapy (HRT) is widely used and has proven benefits for women with menopausal symptoms. An increasing number of women with cancer experience menopausal symptoms but the safety of HRT use in women with cancer is unclear. There are particular concerns that HRT could accelerate cancer progression in women with cancer, and also that HRT could increase the risk of cardiovascular disease in such women. Therefore, our primary aim is to determine whether HRT use alters the risk of cancer-specific mortality in women with a range of common cancers. Our secondary objectives are to investigate whether HRT alters the risk of second cancers, cardiovascular disease, venous thromboembolism and all-cause mortality. METHODS: The study will utilise independent population-based data from Wales using the SAIL databank and Scotland based upon the national Prescribing Information System. The study will include women newly diagnosed with common cancers from 2000 to 2016, identified from cancer registries. Women with breast cancers will be excluded. HRT will be ascertained using electronic prescribing in Wales or dispensing records in Scotland. The primary outcome will be time to cancer-specific mortality from national mortality records. Time-dependent cox regression models will be used to calculate hazard ratios (HR) and 95% confidence intervals (95% CIs) for cancer specific death in HRT users compared with non-users after cancer diagnosis after adjusting for relevant confounders, stratified by cancer site. Analysis will be repeated investigating the impact of HRT use immediately before cancer diagnosis. Secondary analyses will be conducted on the risk of second cancers, cardiovascular disease, venous thromboembolism and all-cause mortality. Analyses will be conducted within each cohort and pooled across cohorts. DISCUSSION: Our study will provide evidence to inform guidance given to women diagnosed with cancer on the safety of HRT use and/or guide modifications to clinical practice.

Weight-lowering Effects of Glucagon-like Peptide-1 Receptor Agonists and Detection of Breast Cancer Among Obese Women with Diabetes.

BACKGROUND: It has been proposed that the weight loss associated with glucagon-like peptide-1 receptor agonists (GLP-1 RAs) may improve detection of breast cancer in patients undergoing this treatment. We aimed to determine whether the weight-lowering effects of GLP-1 RAs are associated with an increased detection of breast cancer among obese women with type 2 diabetes. METHODS: Using the UK Clinical Practice Research Datalink, we conducted a propensity score-matched cohort study among female obese patients with type 2 diabetes newly treated with antidiabetic drugs between 1 January 2007 and 31 January 2018. New users of GLP-1 RAs (n = 5,510) were matched to new users of second- to third-line noninsulin antidiabetic drugs (n = 5,510). We used time-dependent Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of breast cancer associated with different GLP-1 RA maximal weight loss categories (<5%, 5%-10%, >10%). RESULTS: Breast cancer incidence gradually increased with GLP-1 RA maximal weight loss categories, with the highest HR observed for patients achieving at least 10% weight loss (HR = 1.8, 95% CI = 1.1, 2.8). In secondary analyses, the HR for >10% weight loss was highest in the 2-3 years since treatment initiation (HR = 2.9, 95% CI = 1.2, 6.9). CONCLUSIONS: In this population-based study, the detection of breast cancer gradually increased with GLP-1 RA weight loss categories, particularly among those achieving >10% weight loss. These results are consistent with the hypothesis that substantial weight loss with GLP-1 RAs may improve detection of breast cancer among obese patients with type 2 diabetes.

The Risk of Cardiovascular Disease in Prostate Cancer Patients Receiving Androgen Deprivation Therapies.

BACKGROUND: Androgen deprivation therapy (ADT), with a proven role in prostate cancer management, has been associated with various cardiovascular diseases. However, few studies have investigated these associations by type of ADT, particularly for newer ADTs such as the gonadotropin-releasing hormone (GnRH) antagonist degarelix. We investigated the risk of cardiovascular disease by type of ADT in a real-world setting. METHODS: We identified men newly diagnosed with prostate cancer, from 2009 to 2015, from the Scottish Cancer Registry and ADTs from the nationwide Prescribing Information System. Cardiovascular events were based upon hospitalization (from hospital records) or death from cardiovascular disease (from death records). We used Cox regression to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for cardiovascular events with time-varying ADT exposure, comparing ADT users with untreated patients, after adjusting for potential confounders, including prior cardiovascular disease. RESULTS: The cohort contained 20,216 prostate cancer patients, followed for 73,570 person-years, during which there were 3,853 cardiovascular events. ADT was associated with a 30% increase in cardiovascular events (adjusted HR = 1.3; 95% CI = 1.2, 1.4). This reflected increases in cardiovascular events associated with GnRH agonists (adjusted HR = 1.3; 95% CI = 1.2, 1.4), degarelix (adjusted HR = 1.5; 95% CI = 1.2, 1.9), but not bicalutamide monotherapy (adjusted HR = 1.0; 95% CI = 0.82, 1.3). CONCLUSIONS: There were increased risks of cardiovascular disease with the use of GnRH agonists and degarelix, but not with bicalutamide monotherapy. This is the first study to observe increased cardiovascular risks with degarelix, but the cause of this association is unclear and merits further investigation.

Post-diagnostic antipsychotic use and cancer mortality: a population based cohort study.

BACKGROUND: Many antipsychotics elevate prolactin, a hormone implicated in breast cancer aetiology however no studies have investigated antipsychotic use in patients with breast cancer. This study investigated if antipsychotic use is associated with an increased risk of cancer-specific mortality among breast cancer patients. METHODS: A cohort of 23,695 women newly diagnosed with a primary breast cancer between 1st January 1998 and 31st December 2012 was identified from the UK Clinical Practice Research Datalink linked to English cancer-registries and followed for until 30th September 2015. Time-dependent Cox proportional hazards models were used to calculate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of breast cancer-specific mortality comparing use of antipsychotics with non-use, overall, and by prolactin elevating activitiy. Analyses were repeated restricting to patients with a history of severe mental illness to control for potential confounding by indication. RESULTS: In total 848 patients were prescribed an antipsychotic and of which 162 died due to their breast cancer. Compared with non-use, antipsychotic use was associated with an increased risk of breast-cancer specific mortality (HR 2.25, 95%CI 1.90-2.67), but this did not follow a dose response relation. Restricting the cohort to patients with severe mental illness attenuated the association between antipsychotic use and breast cancer-specific mortality (HR 1.11, 95%CI 0.58-2.14). CONCLUSIONS: In this population-based cohort of breast cancer patients, while the use of antipsychotics was associated with increased breast cancer-specific mortality, there was a lack of a dose response, and importantly null associations were observed in patients with severe mental illness, suggesting the observed association is likely a result of confounding by indication. This study provides an exemplar of confounding by indication, highlighting the importance of consideration of this important bias in studies of drug effects in cancer patients.

Prognosis following surgical resection versus local excision of stage pT1 colorectal cancer: A population-based cohort study.

AIMS: To evaluate patient management following stage pT1 colorectal cancer (CRC) diagnosis, and to determine if surgical resection improved outcome compared with local excision, within a population-based study. METHODS: Data were collected from the Northern Ireland Cancer Registry. Cases of stage pT1 CRC diagnosed from 2007 to 2012 were identified. Analyses were conducted using Cox proportional hazard models to calculate hazard ratios (HR) and 95% confidence intervals (CI) for cancer-specific and all-cause mortality for individuals undergoing formal surgery versus local excision. RESULTS: 394 patients with pT1 CRC were included. Of these, 37.1% were treated by local resection, 36.8% had biopsy followed by surgery and 26.1% had local excision followed by surgery. There were 60 deaths over a mean 4.8 years of follow-up, including 10 CRC-specific deaths. An additional 12 patients had a CRC recurrence or metastases during follow-up. Of the CRC-specific deaths or recurrences, 27.3% had local excision only. Individuals treated by formal surgery did not have a reduced risk of CRC-specific death (adjusted HR = 1.51, 95% CI 0.29, 7.89), but did have a reduced risk of all-cause mortality (adjusted HR = 0.51 95% CI 0.30, 0.87) compared with those undergoing local excision only. CONCLUSIONS: Patients with stage pT1 CRC undergoing formal surgery had a reduced risk of all-cause mortality compared with those treated by local excision only. However, this was not explained by a reduced risk of recurrence/disease-free survival or CRC death, and suggests that the observed benefits may simply reflect selection of a healthier patient population in the formal surgery group.

Use of proton pump inhibitors and risk of pancreatic cancer.

PURPOSE: Preclinical studies have suggested that proton pump inhibitors (PPIs) may increase pancreatic cancer risk; however, epidemiological studies are few, with conflicting results. This spurred us to evaluate whether PPI use is associated with an increased risk of pancreatic cancer in a large population-based study. METHODS: We conducted a nationwide case-control study using data from Danish demographic and health care registries. All patients with a first cancer diagnosis of pancreatic cancer between 2000 and 2015 were identified from the Danish Cancer Registry and age-matched, sex-matched, and calendar-matched 1:20 to population controls using risk set sampling. Conditional logistic regression was applied to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for pancreatic cancer associated with PPI use, adjusting for potential confounders. Secondary analyses examined dose-response patterns and associations with individual PPIs as well as with histamine-2-receptor antagonists. RESULTS: Ever use of PPIs occurred among 27.8% of 6921 pancreatic cancer cases and 25.4% of 34 695 matched controls, yielding a neutral adjusted OR of 1.04 (95% CI 0.97-1.11). Odds ratios were also close to unity in analyses of high use of PPIs (≥1000 DDDs; OR, 0.92 95% CI 0.80-1.07). There was no evidence of a dose-response relationship, with ORs close to unity across categories, including for those with the highest cumulative use (>2000 DDDs; OR, 1.03 95% CI 0.84-1.26). Analyses of subgroups as well as individual types of PPI and of histamine-2-receptor antagonists use also returned neutral associations. CONCLUSIONS: In this large nationwide case-control study, PPI use was not associated with an increased risk of pancreatic cancer.

Metformin and the incidence of viral associated cancers in patients with type 2 diabetes.

Limited studies have associated metformin with a reduced risk of viral associated cancers, however these had a number of methodological shortcomings. This study investigated whether the use of metformin is associated with a reduced risk of viral associated cancers in patients with type 2 diabetes. A cohort of 137,754 patients newly-prescribed non-insulin antidiabetic drugs between January 1, 1988 and March 31, 2016 was identified from the UK Clinical Practice Research Datalink and followed until a first-ever diagnosis of a viral associated cancer, death from any cause, end of registration with the practice, or March 31, 2016. Time-varying use of metformin was compared with use of other antidiabetic drugs, with exposures lagged by one year for latency purposes. Time-dependent Cox proportional hazards models were used to estimate adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) of incident viral associated cancer with use of metformin overall, by cumulative duration of use and viral etiology. Overall, there were 424 viral associated cancers during 759,810 person-years of follow-up (crude rate of 5.6 per 10,000 person-years). Metformin was not associated with a decreased rate of viral associated cancer (HR: 0.93, 95% CI: 0.65-1.32). There was no evidence of a duration-response relationship in terms of cumulative duration of use (p trend = 0.69), including with use of metformin for more than 10 years (HR 1.02, 95% CI: 0.52-1.99), or by viral etiology. In this large population-based cohort study, the use of metformin was not associated with a reduced risk of viral associated cancer.

Androgen deprivation therapy for prostate cancer and the risk of hospitalisation for community-acquired pneumonia.

BACKGROUND: Androgens have been shown to influence both the immune system and lung tissue, raising the hypothesis that androgen deprivation therapy (ADT) for prostate cancer may increase the risk of pneumonia. Thus, the aim of this study was to determine whether ADT is associated with an increased risk of hospitalisation for community-acquired pneumonia in patients with prostate cancer. METHODS: This was a population-based cohort study using the United Kingdom Clinical Practice Research Datalink linked to the Hospital Episode Statistics repository. The cohort consisted of 20 310 men newly diagnosed with non-metastatic prostate cancer between 1 April 1998 and 31 March 2015. Time-dependent Cox proportional hazards models were used to estimate adjusted HRs and 95% CIs for hospitalisation for community-acquired pneumonia associated with current and past use of ADT compared with non-use. RESULTS: During a mean follow-up of 4.3 years, there were 621 incident hospitalisations for community-acquired pneumonia (incidence rate: 7.2/1000 person-years). Current ADT use was associated with an 81% increased risk of hospitalisation for community-acquired pneumonia (12.1 vs 3.8 per 1000 person-years, respectively; HR 1.81, 95% CI 1.47 to 2.23). The association was observed within the first six months of use (HR 1.73, 95% CI 1.23 to 2.42) and remained elevated with increasing durations of use (≥25 months; HR 1.79, 95% CI 1.39 to 2.30). In contrast, past ADT use was not associated with an increased risk (HR 1.23, 95% CI 0.95 to 1.60). CONCLUSIONS: The use of ADT is associated with an increased risk of hospitalisation for community-acquired pneumonia in men with prostate cancer.

Androgen Deprivation Therapy and the Risk of Anemia in Men with Prostate Cancer.

BACKGROUND: The use of androgen deprivation therapy in prostate cancer may be associated with an increased risk of anemia, but the evidence remains limited. This study aimed to determine if androgen deprivation is associated with increased risk of anemia in patients newly diagnosed with prostate cancer. METHODS: This was a population-based cohort study using the United Kingdom Clinical Practice Research Datalink linked to the Hospital Episode Statistics repository. The cohort consisted of 10,364 men newly diagnosed with nonmetastatic prostate cancer between 1 April 1998 and 30 September 2015. We used time-dependent Cox proportional hazards models to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for anemia (hemoglobin <130 g/L) associated with current and past use of androgen deprivation therapy, compared with nonuse. RESULTS: There were 3,651 incident anemia events during 31,574 person-years of follow-up (rate: 11.6/100 person-years). Current androgen deprivation therapy use was associated with a nearly three-fold increased hazard of anemia, compared with nonuse (23.5 vs. 5.9 per 100 person-years, respectively; HR: 2.90, 95% CI: 2.67, 3.16). The HR was elevated in the first 6 months of use (HR: 2.20, 95% CI: 1.95, 2.48) and continued to be elevated with longer durations of use. Past androgen deprivation therapy use was associated with a lower estimate (HR: 1.27, 95% CI: 1.12, 1.43), which returned closer to the null ≥25 months after treatment discontinuation (HR: 0.95, 95% CI: 0.79, 1.15). CONCLUSIONS: The use of androgen deprivation therapy is associated with increased risk of anemia, which reverses upon treatment discontinuation.

Adenocarcinoma risk in gastric atrophy and intestinal metaplasia: a systematic review.

BACKGROUND: Gastric cancer (GC) has a poor prognosis with wide variation in survival rates across the world. Several studies have shown premalignant lesions gastric atrophy (GA) and intestinal metaplasia (IM) influence gastric cancer risk. This systematic review examines all available evidence of the risk of GC in patients with GA or IM and explores the geographical variation between countries. METHODS: EMBASE, MEDLINE, Web of Science and the Cochrane Library were searched for relevant articles published to June 2016 investigating the risk of GC in individuals with GA or IM. Analysis was performed to determine variation based on geographical location. Study quality was assessed using the Newcastle-Ottawa Scale and heterogeneity between studies was also evaluated. RESULTS: Fifteen relevant articles were identified, in which there were eight studies of GC incidence in GA and nine in IM cohorts (two articles investigated both GA and IM). The incidence rate of GC in patients with GA ranged from 0.53 to 15.24 per 1000 person years, whereas there was more variation in GC incidence in patients with IM (0.38 to 17.08 per 1000 person years). The greatest GC incidence rates were in Asian countries, for patients with GA, and the USA for those with IM (15.24 and 17.08 per 1000 person years, respectively). The largest studies (four over 25,000 person years) had an incidence rate range of 1.0-2.5 per 1000 person years, however, in general, study quality was poor and there was marked heterogeneity. CONCLUSION: Overall there is a wide variation in annual incidence rate of GC from premalignant lesions. With the recent introduction of surveillance guidelines for gastric atrophy and intestinal metaplasia in the Western world, future assessment of this risk should be performed. Furthermore, substantial heterogeneity supports the need for more robust studies in order to pool results and determine the overall incidence rate of gastric cancer for patients with these premalignant lesions.

Oesophageal adenocarcinoma and prior diagnosis of Barrett's oesophagus: a population-based study.

OBJECTIVE: Endoscopic surveillance of Barrett's oesophagus (BO) provides an opportunity to detect early stage oesophageal adenocarcinoma (OAC). We sought to determine the proportion of OAC patients with a prior diagnosis of BO on a population basis and to evaluate the influence of a prior diagnosis of BO on survival, taking into account lead and length time biases. DESIGN: A retrospective population-based study of all OAC patients in Northern Ireland between 2003 and 2008. A prior BO diagnosis was determined by linkage to the Northern Ireland BO register. Stage distribution at diagnosis and histological grade were compared between patients with and without a prior BO diagnosis. Overall survival, using Cox models, was compared between patients with and without a prior BO diagnosis. The effect of adjusting the survival differences for histological grade and estimates of lead and length time bias was assessed. RESULTS: There were 716 OAC cases, 52 (7.3%) of whom had a prior BO diagnosis. Patients with a prior BO diagnosis had significantly lower tumour stage (44.2% vs. 11.1% had stage 1 or 2 disease; p<0.001), a higher rate of surgical resection (50.0% vs. 25.5%; p<0.001) and had a higher proportion of low/intermediate grade tumours (46.2% vs. 26.5%; p=0.011). A prior BO diagnosis was associated with significantly better survival (HR for death 0.39; 95% CI 0.27 to 0.58), which was minimally influenced by adjustment for age, sex and tumour grade (adjusted HR 0.44; 95% CI 0.30 to 0.64). Correction for lead time bias attenuated but did not abolish the survival benefit (HR 0.65; 95% CI 0.45 to 0.95) and further adjustment for length time bias had little effect. CONCLUSIONS: The proportion of OAC patients with a prior diagnosis of BO is low; however, prior identification of BO is associated with an improvement in survival in OAC patients.

Statin use after diagnosis of breast cancer and survival: a population-based cohort study.

BACKGROUND: Preclinical studies have shown that statins, particularly simvastatin, can prevent growth in breast cancer cell lines and animal models. We investigated whether statins used after breast cancer diagnosis reduced the risk of breast cancer-specific, or all-cause, mortality in a large cohort of breast cancer patients. METHODS: A cohort of 17,880 breast cancer patients, newly diagnosed between 1998 and 2009, was identified from English cancer registries (from the National Cancer Data Repository). This cohort was linked to the UK Clinical Practice Research Datalink, providing prescription records, and to the Office of National Statistics mortality data (up to 2013), identifying 3694 deaths, including 1469 deaths attributable to breast cancer. Unadjusted and adjusted hazard ratios (HRs) for breast cancer-specific, and all-cause, mortality in statin users after breast cancer diagnosis were calculated using time-dependent Cox regression models. Sensitivity analyses were conducted using multiple imputation methods, propensity score methods and a case-control approach. RESULTS: There was some evidence that statin use after a diagnosis of breast cancer had reduced mortality due to breast cancer and all causes (fully adjusted HR = 0.84 [95% confidence interval = 0.68-1.04] and 0.84 [0.72-0.97], respectively). These associations were more marked for simvastatin 0.79 (0.63-1.00) and 0.81 (0.70-0.95), respectively. CONCLUSIONS: In this large population-based breast cancer cohort, there was some evidence of reduced mortality in statin users after breast cancer diagnosis. However, these associations were weak in magnitude and were attenuated in some sensitivity analyses.

Clopidogrel use and cancer-specific mortality: a population-based cohort study of colorectal, breast and prostate cancer patients.

PURPOSE: Concerns were raised about the safety of antiplatelet thienopyridine derivatives after a randomized control trial reported increased risks of cancer and cancer deaths in prasugrel users. We investigate whether clopidogrel, a widely used thienopyridine derivative, was associated with increased risk of cancer-specific or all-cause mortality in cancer patients. METHODS: Colorectal, breast and prostate cancer patients, newly diagnosed from 1998 to 2009, were identified from the National Cancer Data Repository. Cohorts were linked to the UK Clinical Practice Research Datalink, providing prescription records, and to the Office of National Statistics mortality data (up to 2012). Unadjusted and adjusted hazard ratios (HRs) for cancer-specific and all-cause mortality in post-diagnostic clopidogrel users were calculated using time-dependent Cox regression models. RESULTS: The analysis included 10 359 colorectal, 17 889 breast and 13 155 prostate cancer patients. There was no evidence of an increase in cancer-specific mortality in clopidogrel users with colorectal (HR = 0.98 95% confidence interval (CI) 0.77, 1.24) or prostate cancer (HR = 1.03 95%CI 0.82, 1.28). There was limited evidence of an increase in breast cancer patients (HR = 1.22 95%CI 0.90, 1.65); however, this was attenuated when removing prescriptions in the year prior to death. CONCLUSIONS: This novel study of large population-based cohorts of colorectal, breast and prostate cancer patients found no evidence of an increased risk of cancer-specific mortality among colorectal, breast and prostate cancer patients using clopidogrel.

Drugs affecting the renin-angiotensin system and survival from cancer: a population based study of breast, colorectal and prostate cancer patient cohorts.

BACKGROUND: Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) are commonly prescribed to the growing number of cancer patients (more than two million in the UK alone) often to treat hypertension. However, increased fatal cancer in ARB users in a randomized trial and increased breast cancer recurrence rates in ACEI users in a recent observational study have raised concerns about their safety in cancer patients. We investigated whether ACEI or ARB use after breast, colorectal or prostate cancer diagnosis was associated with increased risk of cancer-specific mortality. METHODS: Population-based cohorts of 9,814 breast, 4,762 colorectal and 6,339 prostate cancer patients newly diagnosed from 1998 to 2006 were identified in the UK Clinical Practice Research Datalink and confirmed by cancer registry linkage. Cancer-specific and all-cause mortality were identified from Office of National Statistics mortality data in 2011 (allowing up to 13 years of follow-up). A nested case-control analysis was conducted to compare ACEI/ARB use (from general practitioner prescription records) in cancer patients dying from cancer with up to five controls (not dying from cancer). Conditional logistic regression estimated the risk of cancer-specific, and all-cause, death in ACEI/ARB users compared with non-users. RESULTS: The main analysis included 1,435 breast, 1,511 colorectal and 1,184 prostate cancer-specific deaths (and 7,106 breast, 7,291 colorectal and 5,849 prostate cancer controls). There was no increase in cancer-specific mortality in patients using ARBs after diagnosis of breast (adjusted odds ratio (OR) = 1.06 95% confidence interval (CI) 0.84, 1.35), colorectal (adjusted OR = 0.82 95% CI 0.64, 1.07) or prostate cancer (adjusted OR = 0.79 95% CI 0.61, 1.03). There was also no evidence of increases in cancer-specific mortality with ACEI use for breast (adjusted OR = 1.06 95% CI 0.89, 1.27), colorectal (adjusted OR = 0.78 95% CI 0.66, 0.92) or prostate cancer (adjusted OR = 0.78 95% CI 0.66, 0.92). CONCLUSIONS: Overall, we found no evidence of increased risks of cancer-specific mortality in breast, colorectal or prostate cancer patients who used ACEI or ARBs after diagnosis. These results provide some reassurance that these medications are safe in patients diagnosed with these cancers.

Vaginal Estrogen Therapy Use and Survival in Females With Breast Cancer.

Importance: Genitourinary syndrome of menopause can be treated with vaginal estrogen therapy. However, there are concerns about the safety of vaginal estrogen therapy in patients with breast cancer. Objective: To determine whether the risk of breast cancer-specific mortality was higher in females with breast cancer who used vaginal estrogen therapy vs females with breast cancer who did not use hormone replacement therapy (HRT). Design, Setting, and Participants: This cohort study analyzed 2 large cohorts, one each in Scotland and Wales, of females aged 40 to 79 years with newly diagnosed breast cancer. These population-based cohorts were identified from national cancer registry records from 2010 to 2017 in Scotland and from 2000 to 2016 in Wales and were followed up for breast cancer-specific mortality until 2020. Females were excluded if they had a previous cancer diagnosis (except nonmelanoma skin cancer). Data analysis was performed between August 2022 and August 2023. Exposure: Use of vaginal estrogen therapy, including vaginal tablets and creams, was ascertained from pharmacy dispensing records of the Prescribing Information System for the Scotland cohort and from general practice prescription records for the Wales cohort. Main Outcomes and Measures: The primary outcome was time to breast cancer-specific mortality, which was obtained from national mortality records. Time-dependent Cox proportional hazards regression models were used to calculate hazard ratios (HRs) and 95% CIs for breast cancer-specific mortality, comparing vaginal estrogen therapy users with HRT nonusers and adjusting for confounders, including cancer stage and grade. Results: The 2 cohorts comprised 49 237 females with breast cancer (between 40 and 79 years of age) and 5795 breast cancer-specific deaths. Five percent of patients with breast cancer used vaginal estrogen therapy after breast cancer diagnosis. In vaginal estrogen therapy users compared with HRT nonusers, there was no evidence of a higher risk of breast cancer-specific mortality in the pooled fully adjusted model (HR, 0.77; 95% CI, 0.63-0.94). Conclusions and Relevance: Results of this study showed no evidence of increased early breast cancer-specific mortality in patients who used vaginal estrogen therapy compared with patients who did not use HRT. This finding may provide some reassurance to prescribing clinicians and support the guidelines suggesting that vaginal estrogen therapy can be considered in patients with breast cancer and genitourinary symptoms.