Can breast cancer patients take statins?

After breast surgery ± chemotherapy and radiotherapy, ER+ breast cancer patients start antiestrogenic treatment. Some of these patients – either as a side effect of the antiestrogenic treatment, or also because of the eating beahaviour and  sedentariness – develop hypercholesterolemia. And hypercholesterolemia can be treated with statins (cholesterol lowering medication).

Among other side effects reported by patients during antiestrogenic treatment, the main complain is muscle and joint pain. And among other side effects reported by patients during statins treatment, the main complain is also muscle and joint pain. So – at least because of this shared side effect that can be co-amplified when both treatments are administrated simultaneously – we should first ask the question:

– Can ER+ breast cancer patients take statins during antiestrogenic treatment?

But first, let`s start with a far more important question:

– Can breast cancer patients take statins?

Of course, anyone can take a pill – the second question refering to statins’ carcinogenity and long term safety when administred to breast cancer patients and not to the kinetic ability to swallow a pill.

Epidemiological studies state that statins administration does not increase the risk of cancer – Browning si Martin, 2007. But we don’t have randomised controlled trials that prove statins safety for breast cancer patients.

All we have is a multitude of epidemiological studies with head-to-head contradictory results:

– statins administration in people without cancer:

• is not associated with increased risk of breast cancer – Cauley et al., 2006
• is not associated with decreased risk of breast cancer – Undela, Srikanth and Bansal, 2012
• is associated with increased risk of breast cancer – McDougall et al., 2013
• is associated with decreased risk of triple negative breast cancer – Kumar et al., 2008
• is not associated with decreased risk of triple negative breast cancer – Woditschka et al., 2010

– statins administration in breast cancer patients:

• is associated with a decreased risk of recurrence – Kwan et al., 2008
• is not associated with a decreased risk of recurrence – Nickels et al., 2013
• is associated with a decreased risk of breast cancer mortality – Murtola et al., 2014
• is not associated with a decreased risk of breast cancer mortality – Smith et al., 2016

Despite these contradictory results, one of the systematic reviews of the epidemiological studies on breast cancer and statins connection concluded that statins administration appears to be safe and potentially beneficial for breast cancer patients  (Manthravadi, Shrestha si Madhusudhana, 2016).

So, one: Epidemiological studies – in English, studies that do not prove causality but just raise questions about possible risk factors that should be further tested in randomised controlled trials – claim that statins seem to be safe from an oncological point of view when administered to breast cancer patients, even though we don’t know if this epidemiological hypothesis is true or not.

But – even though statins are among the most sold medications on the planet – paradoxically, the systematic review don by Ravnskov et al. in 2016 shows that people over 60 years of age with high LDL-cholesterol levels leave as much or more than people with low LDL-cholesterol levels.

So, two: The fact that lowering cholesterol by administering statins has a beneficial clinical impact is a generalization not a certainty.

And we know that statins administration side effects associate the main sarcopenic obesity causes:

• sarcopenia (gradual loss of muscle mass) – Wilke et al., 2007 ; Prado et al., 2011
• hyperinsulinism and insulin resistance – Goldstein and Mascitelli, 2013; Aiman, Najmi and Khan, 2014

So, three: Statins administration to breast cancer patients can indirectly increase the risk of obesity.

And breast cancer patients’ obesity increases the risks of metastasis, recurrence and mortality.

References

Aiman, U., Najmi, A., & Khan, R. A. (2014). Statin induced diabetes and its clinical implications. Journal of pharmacology & pharmacotherapeutics, 5(3), 181.

Browning, D. R., & Martin, R. M. (2007). Statins and risk of cancer: a systematic review and metaanalysis. International journal of cancer, 120(4), 833-843.

Cauley, Jane A., et al. “Statin use and breast cancer: prospective results from the Women’s Health Initiative.” Journal of the National Cancer Institute 98.10 (2006): 700-707.

Goldstein, M. R., & Mascitelli, L. (2013). Do statins cause diabetes?. Current diabetes reports, 13(3), 381-390.

Kumar, Anjali S., et al. “Estrogen Receptor–Negative Breast Cancer Is Less Likely to Arise among Lipophilic Statin Users.” Cancer Epidemiology and Prevention Biomarkers 17.5 (2008): 1028-1033.

Manthravadi, S., Shrestha, A., & Madhusudhana, S. (2016). Impact of statin use on cancer recurrence and mortality in breast cancer: A systematic review and meta‐analysis. International journal of cancer, 139(6), 1281-1288.

McDougall, J.A., Malone, K.E., Daling, J.R., Cushing-Haugen, K.L., Porter, P.L. and Li, C.I. (2013) Long-Term Statin Use and Risk of Ductal and Lobular Breast Cancer among Women 55 to 74 Years of Age. Cancer Epidemiology, Biomarkers & Prevention, 22, 1529-1537.

Murtola, Teemu J., et al. “Statin use and breast cancer survival: a nationwide cohort study from Finland.” PloS one 9.10 (2014): e110231.

Nickels, Stefan, et al. “Mortality and recurrence risk in relation to the use of lipid-lowering drugs in a prospective breast cancer patient cohort.” PloS one 8.9 (2013): e75088.

Prado, Carla MM, et al. “Two faces of drug therapy in cancer: drug-related lean tissue loss and its adverse consequences to survival and toxicity.” Current Opinion in Clinical Nutrition & Metabolic Care14.3 (2011): 250-254.

Ravnskov, Uffe, et al. “Lack of an association or an inverse association between low-density-lipoprotein cholesterol and mortality in the elderly: a systematic review.” BMJ open 6.6 (2016): e010401.

Smith, Amelia, et al. “De novo post-diagnosis statin use, breast cancer-specific and overall mortality in women with stage I-III breast cancer.” (2016): 592.

Undela, Krishna, Vallakatla Srikanth, and Dipika Bansal. “Statin use and risk of breast cancer: a meta-analysis of observational studies.” Breast cancer research and treatment 135.1 (2012): 261-269.

Wilke, R.A., Lin, D.W., Roden, D.M., Watkins, P.B., Flockhart, D., Zineh, I., Giacomini, K.M. and Krauss, R.M. (2007) Identifying Genetic Risk Factors for Serious Adverse Drug Reactions: Current Progress and Challenges. Nature S. Moonindranath, H. L. Shen 29 Reviews: Drug Discovery, 6, 904-916

Woditschka, Stephan, et al. “Lipophilic statin use and risk of breast cancer subtypes.” Cancer Epidemiology and Prevention Biomarkers(2010): cebp-0524.