Decreased risk of breast cancer associated with oral bisphosphonate therapy

Preclinical studies and adjuvant trials using bisphosphonates have found them to have an antitumor effect. Although major advances have been made in chemoprevention strategies with selective estrogen receptor modulators and aromatase inhibitors, their use has been fraught with significant adverse effects such as venous thromboembolic events and an increased risk for endometrial cancer. In this context, several recent observational studies have investigated a chemoprevention role for oral bisphosphonates in decreasing risk for breast cancer. This review will aim to summarize these studies and present a critical evaluation of the association between oral bisphosphonate use and breast cancer risk reduction. © 2012 Mathew and Brufsky, publisher and licensee Dove Medical Press Ltd

Possible Roles for Essential Oils in Chemoprevention and Suppression of Cancer

Cancer represents one of the costliest and most prevalent diseases to afflict the modern world, even though treatments have evolved steadily over the years and produce an increasingly positive outlook with each development and innovation. Essential oils have been used medicinally- among other purposes- for thousands of years and have begun to attract attention for possible applications to the field of oncology. Numerous investigations and publications have shed light on the possible chemopreventative (antioxidant and antimetastatic) uses of these oils, alongside cancer suppressive (apoptosis-inducing and cytotoxic) abilities that they may possess. With the high annual incidence of cancer and the ever-rising price of treatment, clinical application of essential oils may transform into a viable and effective compliment to current treatments

Novel applications of COX-2 inhibitors, metformin, and statins for the primary chemoprevention of breast cancer

Recent evidence shows that commonly prescribed drugs, such as non-steroidal anti-inflammatory drugs (NSAIDs), metformin, and statins, may have beneficial roles in the primary chemoprevention of breast cancer. Therefore, these drugs could potentially be used in addition to the hormonal drugs currently used for this purpose (namely, selective estrogen receptor modulators and aromatase inhibitors) due to their alternative mechanisms of action.peer-reviewe

Germline genetic variation in prostate susceptibility does not predict outcomes in the chemoprevention trials PCPT and SELECT

Background The development of prostate cancer can be influenced by genetic and environmental factors. Numerous germline SNPs influence prostate cancer susceptibility. The functional pathways in which these SNPs increase prostate cancer susceptibility are unknown. Finasteride is currently not being used routinely as a chemoprevention agent but the long term outcomes of the PCPT trial are awaited. The outcomes of the SELECT trial have not recommended the use of chemoprevention in preventing prostate cancer. This study investigated whether germline risk SNPs could be used to predict outcomes in the PCPT and SELECT trial. Methods Genotyping was performed in European men entered into the PCPT trial (n = 2434) and SELECT (n = 4885). Next generation genotyping was performed using Affymetrix® Eureka™ Genotyping protocols. Logistic regression models were used to test the association of risk scores and the outcomes in the PCPT and SELECT trials. Results Of the 100 SNPs, 98 designed successfully and genotyping was validated for samples genotyped on other platforms. A number of SNPs predicted for aggressive disease in both trials. Men with a higher polygenic score are more likely to develop prostate cancer in both trials, but the score did not predict for other outcomes in the trial. Conclusion Men with a higher polygenic risk score are more likely to develop prostate cancer. There were no interactions of these germline risk SNPs and the chemoprevention agents in the SELECT and PCPT trials

Chemoprevention of aberrant crypt foci in the colon of rats by dietary onion

Onion intake might reduce the risk of colorectal cancer, according to epidemiology. However, Femia showed in 2003 that diets with a 20% onion intake increase carcinogenesis in rats. We speculated this dose was too high. Prevention of initiation was thus tested in 60 rats given a 5% dried onion diet or AIN76 diet, and initiated 12 days later with azoxymethane (AOM, 1 × 20 mg/kg i.p.), 2-amino-3-methylimidazo[4,5-f]quinoline (IQ, 2 × 200 mg/kg p.o.), or N-nitroso–N–methylurea (2 × 50 mg/kg p.o.). Prevention of promotion was tested in 38 rats given AOM, then randomised to: AIN76 diet; 5% onion diet; phytochemicals diet (supplemented with propyl-disulfide, quercetine-glycosides and oligofructose); 1% pluronic F68 diet (a potent chemopreventive PEG-like block-polymer, used as a positive control). Aberrant crypt foci (ACF) were scored 30 days (initiation) or 100 days (promotion) after carcinogen injection. The onion diet given during initiation reduced the number of AOM-induced ACF (60 versus 86, p = 0.03), and the size of IQ-induced ACF (1.33 versus 1.97, p = 0.02). Given post-initiation, the onion diet reduced the number of ACF (34 versus 59, p = 0.008) and of large ACF (6 versus 15, p = 0.02). Phytochemicals diet and pluronic diet reduced ACF growth similarly. Data show that a 5% onion diet reduced carcinogenesis during initiation and promotion stages, and suggest this chemoprevention is due to known phytochemicals

Preliminary qualitative screening for cancer chemopreventive agents in Telfairia occidentalis Hook.f., Gnetum africanum Welw., Gongronema latifolium Benth. and Ocimum gratissimum L. from Nigeria

The leaves of four plant foods commonly consumed in Nigeria namely Gnetum africanum (Igbo name: Ukazi), Gongronema latifolium (Igbo name: Utazi), Telfairia occidentalis (Igbo name: Ugu), Ocimum gratissimum (Igbo name: Nchoanwu), were each screened for the presence of known potential chemopreventive agents using paper chromatography, thin layer chromatography and various chemical tests. All four vegetables showed the presence of phenolic compounds, flavonoids, phytosterols, tannins, saponins, chlorophyll and glycosides. Only Telfairia occidentalis and Gnetum africanum showed traces of alkaloids

How good are rodent models of carcinogenesis in predicting efficacy in humans? A systematic review and meta-analysis of colon chemoprevention in rats, mice and men

Tumours in rodent and human colon share many histological and genetic features. To know if rodent models of colon carcinogenesis are good predictors of chemopreventive efficacy in humans, we made a meta-analysis of aspirin, beta-carotene, calcium, and wheat bran studies. Controlled intervention studies of adenoma recurrence in human volunteers were compared with chemoprevention studies of carcinogen-induced tumours in rats, and of polyps in Min (Apc(+/-)) mice: 6714 volunteers, 3911 rats and 458 mice were included in the meta-analyses. Difference between models was small since most global relative risks were between 0.76 and 1.00. A closer look showed that carcinogen-induced rat studies matched human trials for aspirin, calcium, carotene, and were compatible for wheat bran. Min mice results were compatible with human results for aspirin, but discordant for calcium and wheat bran (no carotene study). These few results suggest that rodent models roughly predict effect in humans, but the prediction is not accurate for all agents. Based on three cases only, the carcinogen-induced rat model seems better than the Min mouse model. However, rodent studies are useful to screen potential chemopreventive agents, and to study mechanisms of carcinogenesis and chemoprevention

Point: From animal models to prevention of colon cancer. Systematic review of chemoprevention in min mice and choice of the model system.

The Apc(Min/+) mouse model and the azoxymethane (AOM) rat model are the main animal models used to study the effect of dietary agents on colorectal cancer. We reviewed recently the potency of chemopreventive agents in the AOM rat model (D. E. Corpet and S. Tache, Nutr. Cancer, 43: 1-21, 2002). Here we add the results of a systematic review of the effect of dietary and chemopreventive agents on the tumor yield in Min mice. The review is based on the results of 179 studies from 71 articles and is displayed also on the internet http://corpet.net/min.(2) We compared the efficacy of agents in the Min mouse model and the AOM rat model, and found that they were correlated (r = 0.66; P < 0.001), although some agents that afford strong protection in the AOM rat and the Min mouse small bowel increase the tumor yield in the large bowel of mutant mice. The agents included piroxicam, sulindac, celecoxib, difluoromethylornithine, and polyethylene glycol. The reason for this discrepancy is not known. We also compare the results of rodent studies with those of clinical intervention studies of polyp recurrence. We found that the effect of most of the agents tested was consistent across the animal and clinical models. Our point is thus: rodent models can provide guidance in the selection of prevention approaches to human colon cancer, in particular they suggest that polyethylene glycol, hesperidin, protease inhibitor, sphingomyelin, physical exercise, epidermal growth factor receptor kinase inhibitor, (+)-catechin, resveratrol, fish oil, curcumin, caffeate, and thiosulfonate are likely important preventive agents

Specialist recommendation for chemoprevention medications in patients at familial risk of breast cancer: a cross-sectional survey in England

In England, the National Institute for Health and Care Excellence guideline for familial breast cancer recommends chemoprevention for women at high and moderate familial risk of breast cancer. However, prescribing of chemoprevention has not improved since the introduction of the guideline in 2013. The study aims to identify the current practice, in England, of familial cancer specialists offering chemoprevention and recommending prescribing in primary care. This was an anonymised national cross-sectional survey of familial breast cancer risk services in England. Lead clinicians were sent an online survey link. The survey questions included whether chemoprevention was offered/considered for high and moderate risk women, when chemoprevention prescribing and recommendation to primary care started, medications prescribed, age groups considered for chemoprevention and existence of a shared prescribing protocol with primary care. The survey was sent to 115 hospital services, responses from 50 services (43%) were included in the analysis. Of the 40 services offering chemoprevention for high risk women, 15 (38%) did not prescribe but 31 (78%) recommended prescribing to primary care. Of the 31 services considering chemoprevention for moderate risk, eight (26%) did not prescribe with 26 (84%) recommended prescribing to primary care. Only three services reported having a shared protocol with primary care. Within three years of the guidelines, many services recognised the role of chemoprevention for both high and moderate risk with a key role for primary care to initiate prescribing. However, there is still room for improvement