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It has long been hypothesised that aspirin prevents cancer deaths by preventing metastasis. A recent study demonstrates this to be mediated through inhibition of Thromboxane A 2 (TXA2) leading to reversal of suppression of T cell immunity. I appraise the context and future research implications of these findings.

A careful assessment of benefits and harms is required to assess suitability of aspirin as a prophylactic public health measure. However, comprehensive population-level data on harms are lacking. We collected and synthesized age and sex-specific data on harms relevant to aspirin use in average-risk individuals aged 50 years or older. We conducted systematic literature searches to identify baseline rates of gastrointestinal (GI) bleeding, peptic ulcer, major extra-cranial bleeding, and case-fatality rates due to GI bleeding or peptic ulcer in general population. The magnitude of aspirin-associated increase, the prevalence and attributable risk of Helicobacter pylori infection on these events in aspirin users was also assessed. Baseline rates of major extracranial bleeding events and GI complications increase with age; an almost threefold to fourfold increase is observed from age 50-54 to 70-74 years. Low or standard-dose aspirin use increases GI bleeding events by 60 % leading to an annual excess of 0.45 and 0.79 GI bleeding events per 1,000 women and men aged 50-54 years respectively. 5-10 % of major GI complications are fatal; a clear age dependence—higher fatality in older individuals, is seen. Eradication of H.pylori infection before aspirin use could reduce the incidence of upper GI complications by 25-30 %. GI complications are increased by about 60 % due to aspirin use but are fatal only in a very small proportion of individuals younger than 70 years of age. Major bleeding events that are comparable in severity to cancer or CVD, are infrequent. Screening and eradication of H. pylori infection could substantially lower aspirin-related GI harms.

Prostate cancer is a common malignancy in men and the worldwide burden of this disease is rising. Lifestyle modifications such as smoking cessation, exercise, and weight control offer opportunities to reduce the risk of developing prostate cancer. Early detection of prostate cancer by prostate-specific antigen (PSA) screening is controversial, but changes in the PSA threshold, frequency of screening, and the use of other biomarkers have the potential to minimise the overdiagnosis associated with PSA screening. Several new biomarkers for individuals with raised PSA concentrations or those diagnosed with prostate cancer are likely to identify individuals who can be spared aggressive treatment. Several pharmacological agents such as 5α-reductase inhibitors and aspirin could prevent development of prostate cancer. In this Review, we discuss the present evidence and research questions regarding prevention, early detection of prostate cancer, and management of men either at high risk of prostate cancer or diagnosed with low-grade prostate cancer.

Since its first synthesis in 1897, several medicinal roles and mechanisms of action of aspirin have become apparent; the latest among these being its role in cancer prevention and treatment. A large body of evidence supports aspirin’s effect in reducing cancer incidence and cancer mortality, but duration of use needs to be at least 5 years. The beneficial effects are particularly large for colorectal, oesophageal and gastric cancers, with apparently smaller reductions for breast, prostate and lung cancer. The major harm is gastrointestinal bleeding, but serious sequelae are minimal at ages <70 years. It is very likely that use of prophylactic aspirin in the general population aged 50–70+ years will result in net overall benefit. Outstanding issues are: whether standard dose (~300 mg/day) can lead to greater net benefits than low dose (75–100 mg/day), the optimum duration of use, and appropriate ages for use in average-risk individuals.

Background Oncotype DX (ODx) is a 12-gene assay assessing the recurrence risk (high, intermediate, and low) of ductal carcinoma in situ (pre-invasive breast cancer), which guides clinicians regarding prescription of radiotherapy. However, ODx is expensive, time-consuming, and tissue-destructive. In addition, the actual prognostic meaning for the intermediate ODx risk category remains unclear. Methods In this work, we evaluated the ability of quantitative nuclear histomorphometric features extracted from hematoxylin and eosin-stained slide images of 62 ductal carcinoma in situ (DCIS) patients to distinguish between the corresponding ODx risk categories. The prognostic value of the identified image signature was further evaluated on an independent validation set of 30 DCIS patients in its ability to distinguish those DCIS patients who progressed to invasive carcinoma versus those who did not. Following nuclear segmentation and feature extraction, feature ranking strategies were employed to identify the most discriminating features between individual ODx risk categories. The selected features were then combined with machine learning classifiers to establish models to predict ODx risk categories. The model performance was evaluated using the average area under the receiver operating characteristic curve (AUC) using cross validation. In addition, an unsupervised clustering approach was also implemented to evaluate the ability of nuclear histomorphometric features to discriminate between the ODx risk categories. Results Features relating to spatial distribution, orientation disorder, and texture of nuclei were identified as most discriminating between the high ODx and the intermediate, low ODx risk categories. Additionally, the AUC of the most discriminating set of features for the different classification tasks was as follows: (1) high vs low ODx (0.68), (2) high vs. intermediate ODx (0.67), (3) intermediate vs. low ODx (0.57), (4) high and intermediate vs. low ODx (0.63), (5) high vs. low and intermediate ODx (0.66). Additionally, the unsupervised clustering resulted in intermediate ODx risk category patients being co-clustered with low ODx patients compared to high ODx. Conclusion Our results appear to suggest that nuclear histomorphometric features can distinguish high from low and intermediate ODx risk category patients. Additionally, our findings suggest that histomorphometric features for intermediate ODx were more similar to low ODx compared to high ODx risk category.

Guidelines from different organisations regarding the use of aspirin for primary prevention vary despite being based on similar evidence. Translating these in practice presents a further major challenge. The benefit–harm balance tool developed by Puhan et al. ( BMC Med 13:250, 2015) for aspirin can overcome some of these difficulties and is therefore an important step towards personalised medicine. Although a good proof-of-concept, this tool has some important limitations that presently preclude its use in practice or for further research. One of the major benefits of aspirin that has become apparent in the last decade or so is its effect in preventing cancer and cancer-related deaths. However, this benefit is clear and consistent in randomised as well as observational evidence only for specific cancers. Additionally, it has long lag-time and carry-over periods. These nuances of aspirin’s effects demand a specific and a more sophisticated model such as a time-varying model. Further refinement of this tool with respect to these aspects is merited to make it ready for evaluation in qualitative and quantitative studies with the goal of clinical utility. Please see related article: http://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-015-0493-2

The concept of cancer cells being hierarchically organized and arising from their own progenitor stem cells will have important implications on cancer therapy. If this hypothesis were to be true then the paucity of estrogen receptors in stem cells as well as their inherent drug resistance mechanisms pose a challenge to current targeted therapies. In this study, we sought to examine the prognostic relevance of ALDH1, a putative cancer stem cell marker, by immunohistochemistry. The four cohorts analyzed included an adjuvantly treated series of 245 invasive cancers, a neoadjuvantly treated series of 34 cases, and two series of 58 and 40 triple negative cases, respectively. Both tumor cell and stromal expression for ALDH1 was evaluated, where possible. Tumor cell ALDH1 expression significantly correlated only with basal-like and HER2 tumor types in the adjuvant series and tumor grade in the neoadjuvant cohort. No significant enrichment for ALDH1 positive cells was observed in the postneoadjuvant therapy specimens compared to pretreatment samples. On the other hand, high degree of stromal expression was significantly associated with best disease-free survival as well as a trend for overall survival. The association of stromal expression was confirmed in an independent cohort of triple negative cases. The novel finding is that tumor microenvironment may play a significant role in determining the prognostic impact of stem/progenitor cells in human breast tumors.

Several medical therapies modify the risk of developing certain cancers in an individual. The aim of this paper was to provide the scientific justification for the 5th edition of the European Code Against Cancer (ECAC5) recommendation on the use of hormone replacement therapy (HRT) and other drugs used at population scale, such as hormonal contraceptives and aspirin. HRT modifies the risk of developing certain cancers in an individual. Except for vaginal oestrogens, all forms of HRT are associated with an increased breast cancer risk; the risk of serous ovarian cancer and endometrial cancer may also be increased. Despite such an increase in cancer risk, HRT often remains the only option for the management of certain menopausal symptoms for the restoration of quality of life and mental health. Therefore, the ECAC5 recommends using HRT for bothersome menopausal symptoms only after a thorough discussion with a healthcare professional and limiting its use for as short a duration as possible. On review of up‐to‐date evidence for hormonal contraceptives and aspirin, the ECAC5 Working Group elected not to make a recommendation for the average‐risk general population regarding the use of these therapies.

Strategies to increase physical activity (PA) and improve nutrition would contribute to substantial health benefits in the population, including reducing the risk of several types of cancers. The increasing accessibility of digital technologies mean that these tools could potentially facilitate the improvement of health behaviours among young people. We conducted a review of systematic reviews to assess the available evidence on digital interventions aimed at increasing physical activity and good nutrition in sub-populations of young people (school-aged children, college/university students, young adults only (over 18 years) and both adolescent and young adults (<25 years)). Searches for systematic reviews were conducted across relevant databases including KSR Evidence (www.ksrevidence.com), Cochrane Database of Systematic Reviews (CDSR) and Database of Abstracts of Reviews of Effects (DARE; CRD). Records were independently screened by title and abstract by two reviewers and those deemed eligible were obtained for full text screening. Risk of bias (RoB) was assessed with the Risk of Bias Assessment Tool for Systematic Reviews (ROBIS) tool. We employed a narrative analysis and developed evidence gap maps. Twenty-four reviews were included with at least one for each sub-population and employing a range of digital interventions. The quality of evidence was limited with only one of the 24 of reviews overall judged as low RoB. Definitions of \"digital intervention\" greatly varied across systematic reviews with some reported interventions fitting into more than one category (i.e., an internet intervention could also be a mobile phone or computer intervention), however definitions as reported in the relevant reviews were used. No reviews reported cancer incidence or related outcomes. Available evidence was limited both by sub-population and type of intervention, but evidence was most pronounced in school-aged children. In school-aged children eHealth interventions, defined as school-based programmes delivered by the internet, computers, tablets, mobile technology, or tele-health methods, improved outcomes. Accelerometer-measured (Standardised Mean Difference [SMD] 0.33, 95% Confidence Interval [CI]: 0.05 to 0.61) and self-reported (SMD: 0.14, 95% CI: 0.05 to 0.23) PA increased, as did fruit and vegetable intake (SMD: 0.11, 95% CI: 0.03 to 0.19) (review rated as low RoB, minimal to considerable heterogeneity across results). No difference was reported for consumption of fat post-intervention (SMD: -0.06, 95% CI: -0.15 to 0.03) or sugar sweetened beverages(SSB) and snack consumption combined post-intervention (SMD: -0.02, 95% CI:-0.10 to 0.06),or at the follow up (studies reported 2 weeks to 36 months follow-up) after the intervention (SMD:-0.06, 95% CI: -0.15 to 0.03) (review rated low ROB, minimal to substantial heterogeneity across results). Smartphone based interventions utilising Short Messaging Service (SMS), app or combined approaches also improved PA measured using objective and subjective methods (SMD: 0.44, 95% CI: 0.11 to 0.77) when compared to controls, with increases in total PA [weighted mean difference (WMD) 32.35 min per day, 95% CI: 10.36 to 54.33] and in daily steps (WMD: 1,185, 95% CI: 303 to 2,068) (review rated as high RoB, moderate to substantial heterogeneity across results). For all results, interpretation has limitations in terms of RoB and presence of unexplained heterogeneity. This review of reviews has identified limited evidence that suggests some potential for digital interventions to increase PA and, to lesser extent, improve nutrition in school-aged children. However, effects can be small and based on less robust evidence. The body of evidence is characterised by a considerable level of heterogeneity, unclear/overlapping populations and intervention definitions, and a low methodological quality of systematic reviews. The heterogeneity across studies is further complicated when the age (older vs. more recent), interactivity (feedback/survey vs. no/less feedback/surveys), and accessibility (type of device) of the digital intervention is considered. This underscores the difficulty in synthesising evidence in a field with rapidly evolving technology and the resulting challenges in recommending the use of digital technology in public health. There is an urgent need for further research using contemporary technology and appropriate methods.