1 June 2011
Stress response and the metastasis of breast cancer.
Researchers based at Trinity College Dublin have discovered that blocking a particular stress response can significantly reduce the metastasis (or spread) of breast cancer.
Recently published research lead by Dr Ian Barron, a HRB Postdoctoral Fellow in Pharmacology and Therapeutics at Trinity College Dublin (TCD) looked at women diagnosed with breast cancer in Ireland between 2000 and 2007. Using data from the National Cancer Registry, and the HSE Primary Care Reimbursement Services, they found that those taking drugs that blocked a particular hormone related stress pathway had a much lower risk of dying from their cancer.
According to Dr Barron,
" For patients with cancer, higher levels of stress are associated with more frequent disease recurrence, faster disease progression and higher rates of death from cancer. Some lab based studies have suggested how stress hormones such as adrenaline and noradrenaline, could play a role in this process. Ours is the first study in humans to show that blocking this stress response significantly reduces the risk of cancer spreading or metastasising. Because the majority of all cancer deaths are due to the growth of tumour metastases, this research could have significant implications for clinical practice."
The research found that when compared to control groups;
- Women taking the stress hormone blocking drugs in the year prior to their cancer diagnosis were less likely to be diagnosed with invasive or metastatic breast cancer than women who were not taking it.
- Women continuing to take the drug after their diagnosis were considerably less likely to die from the disease in the 5 years following diagnosis.
Enda Connolly, Chief Executive of the Health Research Board added,
" This is a great example of the high quality health research conducted in Ireland. As the findings clearly demonstrate, it has positive implications for patient care and patient outcomes and could have major international impact."
More about this research into Beta Blockers and Breast Cancer Mortality:
Cancer and Stress:
- Observational studies looking at factors that cause cancer or affect its outcomes (i.e. recurrence, progression or death) have shown that:
- Stress may increase the risk of having cancer.
- In patients with cancer, higher levels of stress are associated with more frequent disease recurrence, faster disease progression and higher rates of death from cancer.
- Stress in these studies has been defined in a number of ways but most commonly as: stress/anxiety, depression, lack of social support, marital discord etc.
- Based on the results from these epidemiologic studies, pre-clinical laboratory studies have been undertaken by a number of research groups to try and identify exactly how stress influences tumour progression.
- Breast cancer patients taking a drug that inhibits the beta 2 adrenergic receptor would be less likely to have invasive or metastatic disease at the time of their diagnosis.
- Breast cancer patients continuing to take this drug after their diagnosis of breast cancer would have a lower risk of death due to their breast cancer.
- The study involved a retrospective observational cohort study using information relating to breast cancer cases from the National Cancer Registry Ireland database and information on prescribed medication use from the HSE PCRS prescription refill database.
- The study included women diagnosed with breast cancer in Ireland between 2000 and 2007.
- It considered the use of medicines from a class of drug known as beta-blockers. These drugs are already used by a significant number of patients in Ireland to treat cardiovascular conditions; such as, hypertension (high blood pressure) or heart failure. Some beta-blockers can also be prescribed to prevent migraines and to control tremors. Their mechanism of action is to block either or both of the beta 1 and beta 2 adrenergic receptors. There are a wide variety of bet-blockers available and each has varying activity on the beta 1 & beta 2 adrenergic receptors. The beta-blockers that we looked at in our study were:
- Propranolol: This was the drug of main interest in our study. Propranolol has both beta 1 and beta 2 adrenergic receptor antagonist activity. It is prescribed for cardiovascular indications but can also be used for the control of tremor and migraine prevention.
- Atenolol: This beta-blocker has only beta 1 receptor antagonist activity and was included in our study to demonstrate that the observed effects of propranolol were most likely mediated through its beta 2 receptor activity not its beta 1 receptor activity.
- Possible outcomes investigated:
- (1): Women taking propranolol in the year prior to their breast cancer diagnosis were compared to a matched sample of women not taking propranolol. We then looked to see if women taking propranolol were less likely, at diagnosis, to have
- Breast cancer that had spread to the chest wall around the breast or the skin of the breast.
- Breast cancer that had spread to the local lymph nodes (the first place outside the breast that a breast tumour normally spreads to)
- Breast tumour cells that had spread to other parts of the body beyond the breast and local lymph nodes (i.e. metastatic disease)
- (2): Women continuing to take propranolol after their breast cancer diagnosis were compared to a matched sample of women not taking propranolol. We then looked to see if women taking propranolol were less likely to have died from breast cancer over the next 5 years.
Results of the Study:
- Women taking the beta 2 receptor antagonist – propranolol - in the year prior to their breast cancer diagnosis were significantly less likely to be diagnosed with locally advanced (i.e. a tumour that has spread to the local lymph nodes, chest wall or skin of the breast) or metastatic breast cancer when compared to women not taking propranolol.
- Women continuing to take propranolol after their breast cancer diagnosis were considerably less likely to die from their breast cancer in the 5 years following diagnosis.
- As expected from pre-clinical work, the inhibition of the beta 1 adrenergic receptor by atenolol had no effect on any of the outcomes. This suggests that the observed effects of propranolol, which blocks both beta 1 and beta 2, are mediated through its effects on the beta 2 adrenergic receptor.
What does this mean
- Results suggest that inhibition of the beta 2 adrenergic receptor, by propranolol, can reduce the development of metastases in breast cancer patients. This is important because the development of metastases are associated with potentially incurable breast cancer.
- Results also suggest that women with breast cancer who are taking propranolol have a considerably reduced risk of dying from their breast cancer.
Reference to Paper:
Thomas I. Barron, Roisin M. Connolly, Linda Sharp, Kathleen Bennett and Kala Visvanathan, "Beta Blockers and Breast Cancer Mortality: A Population-Based Study", Journal of Clinical Oncology, 31 May 2011.
Source: Health Research Board (Ireland).
http://www.hrb.ie - and associated information available as downloads.