Beta-Blockers and Cancer?



Fight or Flight! That's often what I feel like I'm doing on a daily basis!

I take a number of pills daily based numerous studies. In addition to aspirin, I have recently started to take propranolol. Propranolol is a non-selective Beta (β) blocker. This means that it blocks both β1 and β2 adrenergic receptors (AR). These receptors play a key role in your sympathetic nervous system ("fight or flight"). There have been many studies looking at β-ARs and cancer because β-AR stimulation promotes the infiltration of macrophages (immune cells) into the tumor and induces pro-metastatic gene expression and signature. This leads to an increase in COX-2, MMP-9, and VEGF expression, all tumor-promoting signals. In fact, beta signaling increased blood vessel growth by 3 fold! There is also evidence that β-AR stimulation suppresses natural killer (NK) cell activity, very important immune cells that fight against any circulating tumor cells (CTCs).

Studies on Beta-blockers

There have been at least 6 studies showing a benefit for breast cancer patients who have taken β-blockers and a good meta-analysis by Barron, et all published in Therapeutic Advances in Medical Oncology in May, 2012 summarizes these articles. In a study published in the Journal of Clinical Oncology, this benefit was only seen in patients with TNBC. However, the authors do observe that such differences may be related to the earlier recurrence rates seen in TNBC. There are drawbacks to most of these studies that lead doctors to hesitate prescribing a medication with many potential side-effects. There are also issues with observational studies (see the website of the National Cancer Institute) such as accuracy of data retrieved from pharmacies, patient reporting, etc. We would like to see a good randomized controlled trial (see the website of the National Cancer Institute for the definition) addressing propranolol. I should also note that the selective β-blockers did not show benefit (medications such as atenolol). Also see the brief summary on www.stopcancerfund.org.

My Take

I take propranolol because I believe there is merit to these studies and it makes physiologic sense to me. We are becoming increasingly aware of the effects of stress on our immune systems and possibly cancer recurrence and growth. When I examined the medications that I considered taking, I initially asked myself if the medication could serve a dual purpose and cause little to no side-effects that would affect my quality of life. In addition to potentially being able to prevent cancer metastases, propranolol can protect the heart against the effects of my chemotherapeutic regimen. I don't suffer from migraines, but it is also an excellent prophylaxis medication for those who do. Propranolol is also useful for anxiety and benign tremors. I started at 10 mg daily and worked my way up to the 60 mg long-acting formulation so that I would be taking the average dosage used in most studies. This is also the dosage for migraine prophylaxis. I have a very involved PCP who assisted me with this (yes, even though I am a doctor) and you must always work closely with your doctor when taking any new medications including OTC vitamins and medications. Propranolol has a host of potential side-effects, many of which are deadly. Therefore, the cost versus benefit of this medication may not make sense for many people.

The following are additional studies related to stress and breast cancer metastases:

1. Sloan EK, Priceman SJ, Cox BF, et al. The sympathetic nervous system induces a metastatic switch in primary breast cancer. Cancer Res. 70:7042–7052. [PMC free article] [PubMed] 2. Tangir J, Bonafé N, Gilmore-Hebert M, et al. SGK1, a potential regulator of c-fms related breast cancer aggressiveness. Clin Exp Metastasis. 2004;21:477–483. [PubMed] 3. Chrousos GP, Gold PW. The concepts of stress and stress system disorders: Overview of physical and behavioral homeostasis. JAMA. 1992;267:1244–1252. [PubMed] 4. Melhem-Bertrandt A, Conzen S. The relationship between psychosocial stressors and breast cancer biology. Curr Breast Cancer Rep. 2010;2:130–137. 5. Andersen BL, Yang HC, Farrar WB, et al. Psychologic intervention improves survival for breast cancer patients: A randomized clinical trial. Cancer. 2008;113:3450–3458. [PMC free article] [PubMed]

*Do not take this during chemotherapy, radiation therapy, or after treatment without consulting your doctor.

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