Women with breast cancer are commonly treated with aromatase inhibitors (AIs) and tamoxifen which block the action of estrogens in the body. Nevertheless, three recent studies conducted in the real-world setting indicated that long-term treatment with tamoxifen may increase the risk of Parkinsons Disease (PD). These findings are concerning given that women treated with tamoxifen represent older patients who are already at increased risk of PD. However, these studies had several limitations in their design and an inadequate number of patients to confidently assess long-term effect of tamoxifen on PD. Thus, the objective of this study is to address limitations of previous studies and compare the risk of PD associated with use of anti-estrogens (AIs and tamoxifen) in comparison to non-use of these drugs. We will address this question in the general population of post-menopausal women in the CPRD and in post-menopausal women newly diagnosed with breast cancer. We will also independently examine the association between tamoxifen and AIs and the risk of PD and evaluate the long-term effect of these drugs. This study should provide clinicians and patients with strong evidence regarding the risk of PD associated with anti-estrogens in the real-world setting.
Tamoxifen and aromatase inhibitors (AIs) are widely used for treatment of hormone-receptor positive breast cancer in women. Tamoxifen is a competitive inhibitor of estrogens action on estrogen-receptors. It has been proposed that tamoxifen thus may counter the neuroprotective action of estrogen. However, findings from observational studies regarding the effect of endogenous and exogenous estrogens on Parkinsons Disease (PD) have been inconsistent.
Three recent observational studies have reported that long-term use of tamoxifen (more than six years of cumulative use) is associated with an increased risk of PD. These results are of concern given that women treated with tamoxifen represent an older patient population already at increased risk PD. However, these studies should be interpreted with caution as they had methodological limitations and were not powered to assess the impact of long-term use of tamoxifen and thus the increased risk observed after six years of cumulative use of tamoxifen may be due to chance finding. Thus, the objective of this study is to conduct a large-scale observational study with appropriate methodology to assess the risk of PD associated with use of anti-estrogens (AIs and tamoxifen) in comparison to no-use of anti-estrogens. The study will be conducted in a cohort of post-menopausal women in the general population in CPRD and in a cohort of post-menopausal women newly diagnosed with breast cancer. In secondary analyses, the risk of PD associated with tamoxifen and AIs will be assessed independently. We will also examine the effect of cumulative duration of use of these drugs on risk of PD. This study should provide clinicians and patients with strong evidence regarding the risk of PD associated with tamoxifen and AIs in the real-world setting of clinical practice.
We will identify all patients within our cohort with a first-time read code for PD recorded any time after cohort entry. The diagnostic code for PD has been previously validated in the CPRD.
Samy Suissa - Chief Investigator - Sir Mortimer B Davis Jewish General Hospital
Christel Renoux - Corresponding Applicant - McGill University
Farzin Khosrow-Khavar - Collaborator - Sir Mortimer B Davis Jewish General Hospital
Francois Montastruc - Collaborator - University Of Toulouse
Jean-Louis Montastruc - Collaborator - University Of Toulouse
Laurent Azoulay - Collaborator - McGill University
Sophie Dell'Aniello - Collaborator - McGill University