Study: Statins may reduce cancer-related mortality

reference

Nielsen SF, Nordestgaard BG, Bojesen SE. Statin use and reduced cancer-related mortality.N Engl J Med. November 8, 2012;367(19):1792-1802.

design

Danish researchers examined whether taking statins before a cancer diagnosis is associated with reduced cancer-related mortality. They examined the mortality of patients from the entire Danish population who received a cancer diagnosis between 1995 and 2007, with follow-up until December 31, 2009. Of the patients aged 40 years or older, 18,721 had taken statins regularly before the cancer diagnosis and 277,204 had never used statins.

Results

Statin users were 15% less likely to die from any cause or cancer. Reduced cancer-related mortality among statin users was observed for each of the 13 cancer types.

Effects on practice

This study, along with several other recent works, deserves our attention. If these results are real, we should consider prescribing statins to many more of our patients rather than discouraging their use.

In particular, we should consider prescribing statins to patients with breast cancer. In April 2013, Dr. Teemu Murtola said at the annual meeting of the American Association for Cancer Research that statin use was associated with a reduction in the risk of death from breast cancer by up to 66%.

Murtola et al. conducted their retrospective study examining statin use and breast cancer mortality in 31,114 women with breast cancer diagnosed between 1995 and 2003 in Finland. During follow-up, 6,011 of the women died; 3,169 due to breast cancer. The mortality rate was 7.5% for statin users, while it was 21% for non-statin users.
In other words, women with localized disease who took statins had a 67% lower risk of death than non-users (risk ratio 0.33). In patients with metastatic disease, statins reduced the risk of death by 48% (HR 0.52). Finland's national health database enabled detailed analysis so that the reduced risk of death could be calculated based on the type of statin taken: including simvastatin (HR 0.47), atorvastatin (HR 0.27), fluvastatin (HR 0.35) and pravastatin (HR 0.47). 0.50). The median follow-up time was approximately 3 years but varied from less than 1 year to 9 years.¹

Statins have an image in alternative medicine circles that is hard to shake. They are often considered the best example of everything that is wrong with Big Pharma. They are considered overpriced drugs that are over-marketed and over-prescribed while the risks associated with consumption are underestimated. Therefore, we are obliged to look for other explanations for these results.

Nielsen argues that their results "...are plausible because statins inhibit cholesterol synthesis in cells by inhibiting 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCoA), the rate-limiting enzyme in the mevalonate and cholesterol synthesis pathway. Many of these downstream products are involved in the Cell proliferation is used because they are required for critical cellular functions such as maintaining membrane integrity, signal transduction, protein synthesis, and cell cycle progression. Disturbances of these processes in malignant cells lead to inhibition of cancer growth and metastasis.”

Plausible yes, but they are still not easy for us to accept. Statins have an image in alternative medicine circles that is hard to shake. They are often considered the best example of everything that is wrong with Big Pharma. They are considered overpriced drugs that are over-marketed and over-prescribed while the risks associated with consumption are underestimated. Therefore, we are obliged to look for other explanations for these results.

Siddarth Singh of the Mayo Clinic writes in the May issue ofWorld Journal of Clinical Oncologyprovides several alternative explanations for Nielsen's results, suggesting that several confounding factors were not taken into account. Firstly, data on smoking were not taken into account. Patients may have stopped smoking when they started taking statins, possibly after having recently suffered a myocardial infarction. Reducing or stopping smoking among statin users could lead to a lower risk of mortality.
Another possible explanation is the so-called “healthy user effect” and also the “healthy adherer effect”. Doctors may unknowingly but selectively underprescribe statins to obese patients or smokers due to their unhealthy lifestyles. This could also change mortality.

The third option is to take other medicines with anti-cancer effects at the same time.

In Nielsen's study, women who took statins had higher rates of cardiovascular disease (70% vs. 21%) and diabetes (18% vs. 3%) than women who didn't take statins. This may have led to a disproportionately higher use of aspirin and metformin among statin users. Both are associated with reduced cancer-related mortality. Nielsen re-examined the data for this possible aspirin use and excluded any participants with cardiovascular disease (the only indication in Denmark for routine aspirin use). The analysis gave the same results.²

Still, it is hard to forget that the meta-analysis of 51 randomized controlled trials by Rothwell et al. in 2012 found that aspirin users had a 15% lower risk of dying from cancer (OR = 0.85; 95% CI: 0.76-0.96).

There are other studies that provide data that contradicts both the Nielsen and Murtola studies.

A 2012 meta-analysis of statin use and the risk of developing breast cancer found no significant benefit. “A total of 24 (13 cohort and 11 case-control studies) with more than 2.4 million participants, including 76,759 breast cancer cases, contributed to this analysis... Statin use and long-term statin use had no significant effect on breast cancer risk (RR = 0.99, 95% CI = 0.94, 1.04 and RR =, respectively 1.03, 95% CI = 0.96, 1.11).”⁴Obviously, these results relate to the risk of developing breast cancer, not the risk of dying from it.

It could be argued that statins are actually beneficial after a breast cancer diagnosis.

Swedish data published in April 2013 suggests that there may be a way to predict which cancers will respond to statin treatment. Bjarnadottir et al. treated 50 women diagnosed with invasive breast cancer with high-dose atorvastatin (i.e., 80 mg/day) for two weeks before cancer surgery. Tissue samples before and after statin therapy were compared. On average, when considering all paired samples, Ki67 expression did not significantly decrease after statin treatment by only 7.6% (P=0.39), but in tumors expressing HMG-CoA reductase (HMGCR), the rate-limiting enzyme of the mevalonate signaling pathway, Ki67 decreased significantly by 24% (P=0.02). Statins have the strongest antiproliferative effect in HMGCR-positive tumors. Thus, testing for HMGCR may provide an opportunity to selectively treat cancer patients who respond favorably to statins and benefit from treatment.5

The studies by Nielsen and Murtola are exciting. In the long run, their results may or may not hold up. The question now is whether we encourage patients, particularly breast cancer patients, to take statin drugs or wait a few years in the hope that large, definitive, prospective, randomized, controlled trials provide definitive answers.

Murtola's data in particular is convincing. If this is true, statins may reduce the risk of death from breast cancer more than other adjuvant therapies used. Although statins pose risks, these appear to be of a lower magnitude than those currently considered routine cancer therapies. When we weigh risk and benefit, the scales begin to tip toward statins.

For more research on integrative oncology, click here Here.