Time and again, various substances are praised as “anticancer agents,” both in scientific circles and in the lay press. A symposium at this year’s ASCO Congress in Chicago was dedicated to this topic. Is there scientific evidence to swallow aspirin, vitamin D, or metformin to prevent cancer?
(ee) There is a great interest in using already existing substances as “anticancer agents”. Agents that have been in use for some time have important advantages, such as known safety and toxicity profiles and lower costs compared to newly developed substances.
With regard to their anti-cancer effects, metfomine, acetylsalicylic acid, beta-blockers, folic acid and vitamin D, among others, are being studied. Such analyses are often triggered by observational studies or epidemiological studies that show that the active ingredient in question is not present in people who take or use the active ingredient in question. taking, the risk of cancer or cancer mortality is reduced. Often, however, these observations cannot be verified because of methodological flaws in the original studies. Pamela Jean Goodwin, MD, Toronto, Canada, and John Baron, University of North Carolina, USA, presented the current data on various substances in their talks.
Metformin
Metformin is an orally taken substance for the treatment of type 2 diabetes that improves glucose metabolism. There was a real hype around metformin as an anti-cancer agent, based mainly on data from observational studies. Metformin could in principle have a direct (insulin-independent) or indirect (by lowering glucose and insulin levels) anticancer effect [1]. In several meta-analyses, metformin use was associated with a reduced risk of colorectal cancer, breast cancer, pancreatic cancer, and hepatocellular carcinoma. Other studies showed that diabetics treated with metformin had lower cancer-specific and overall mortality than diabetics who did not take metformin. However, the follow-up time was very short in most studies, exceeding 2.5 years in only five studies.
The best evidence is for the association with breast cancer [2]. Chlebowsi et al. found a lower incidence of breast cancer in diabetic women who had received metformin than in non-diabetic women and diabetic women who had been treated without metformin. In addition, there is evidence that women who have taken metfomin and who already have breast cancer have a higher response rate to neoadjuvant cancer therapy than other women. The hypothesis that metformin can improve the outcome of breast cancer is currently being tested in a phase III trial: Around 3700 patients with early-stage breast cancer are receiving metformin or placebo for five years in addition to standard therapy. Results are expected in three years.
Although there are some studies linking metformin to reduced cancer risk, the formal shortcomings of the relevant studies are nevertheless large. Currently, metformin cannot be recommended as an anticancer agent, either for the prevention or treatment of cancer. The potential anti-cancer effect of metformin is currently being investigated in two other phase III studies in addition to the breast cancer study already mentioned. In the first, patients with early-stage prostate cancer will receive metformin or placebo, with the endpoint being the duration to disease progression. In the second, the chemopreventive effect of metformin regarding endometrial cancer is investigated. Women with obesity or high insulin levels will be recruited.
Vitamin D
Vitamin D is absorbed in the intestine on the one hand, and is also produced in the skin under the influence of sunlight on the other. Interest in vitamin D as an anticancer agent stems primarily from environmental studies that showed that cancer incidence was higher in countries with low sun exposure than in countries near the equator. In addition to low sun exposure, inadequate vitamin D intake and low blood levels of vitamin D have been associated with increased cancer risk. Two years ago, the Institute of Medicine reviewed the existing literature and postulated that there is no association between vitamin D and cancer risk [3].
Most existing studies examining blood levels of vitamin D and cancer risk have focused on individual cancer types. Increased cancer risk at low vitamin D levels was found for pancreatic cancer, colorectal cancer, and breast cancer. Few studies have examined the effect of vitamin D supplementation on cancer risk – the results are conflicting. Whether vitamin D administration in pre-existing cancer can positively influence outcome is also controversial.
Non-steroidal anti-inflammatory drugs
Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit proliferation and increase apoptosis in vitro. Several observational and case-control studies showed that regular use of acetylsalicylic acid reduces the risk of colorectal cancer. However, this requires that the active ingredient be taken continuously over a long period of time. High doses are not necessary, but it is possible that higher doses also produce greater risk reduction. It takes five to ten years (latency period) before there is a demonstrable reduction in risk. It remains to be seen whether cancer risk is reduced equally in all people or whether the effect is stronger in certain high-risk populations. However, the toxic side effects of acetylsalicylic acid must not be forgotten. It is not currently recommended as a cancer prevention agent.
Source: 50th Annual Meeting of the American Society of Clinical Oncology (ASCO), May 30-June 3, 2014, Chicago.
Literature:
- Dowling RJ, et al: Metformin in cancer: translational challenges. J Mol Endocrinol 2012; 48(3): R31-43. doi: 10.1530/JME-12-0007. print 2012 Jun. Review.
- Chlebowski RT, et al: Diabetes, metformin, and breast cancer in postmenopausal women. J Clin Oncol 2012; 30(23): 2844-2852. doi: 10.1200/JCO.2011.39. 7505. epub 2012 Jun 11.
- Rosen CJ, et al: IOM committee members respond to Endocrine Society vitamin D guideline. J Clin Endocrinol Metab 2012; 97(4): 1146-1152. doi: 10.1210/jc. 2011-2218. epub 2012 Mar 22.
