Previous studies have indicated that tamoxifen may increase long-term risk of Parkinson's disease. But until now, no trial has directly compared the risk of developing the chronic illness after using aromatase inhibitors or tamoxifen for breast cancer treatment. In a recent study published in the journal Cancer, researchers analyzed health records from more than 30,000 women over age 50 who had previously been diagnosed with non-metastatic breast cancer and were newly treated with either aromatase inhibitors or tamoxifen (2022; https://doi.org/10.1002/cncr.34208). For up to 12 years after the start of treatment, there was no increased risk of Parkinson's disease in women taking either treatment.
"This study provides an important addition to the long-term safety profile of aromatase inhibitors compared with tamoxifen in this patient population," noted Farzin Khosrow-Khavar, PhD, the study's lead author and Postdoctoral Research Fellow at Brigham and Women's Hospital. "Although additional studies will be needed for corroboration of our findings, the results from this study may provide physicians and patients with reassurance regarding the risk of Parkinson's disease with aromatase inhibitors compared with tamoxifen in the management of postmenopausal women diagnosed with breast cancer."
1 Why did you and your team conduct this research now?
"Current clinical guidelines recommend treatment of postmenopausal women who are diagnosed with hormone receptor-positive breast cancer with either aromatase inhibitors or tamoxifen. Importantly, recent guidelines indicate long-term treatment with these drugs for up to 10 years. These drugs act by depleting estrogen levels in postmenopausal women. Some have hypothesized that estrogen may protect against onset and progression of Parkinson's disease through neuroprotective mechanisms.
"When deciding on optimal treatment choice between aromatase inhibitors and tamoxifen, the comparative effectiveness of these drugs in clinical practice may be weighed against their differential safety profile. However, no studies have assessed the risk of Parkinson's disease with aromatase inhibitors compared with tamoxifen.
"Aromatase inhibitors are being increasingly prescribed as they have shown improvement in overall survival and breast cancer-related mortality compared with tamoxifen. Thus, our study aimed to provide information on the risk of Parkinson's disease with aromatase inhibitors compared with tamoxifen to help inform optimal treatment choice in patients with breast cancer."
2 Can you explain why you used the dataset you did to investigate this question?
"We used the Clinical Practice Research Datalink (CPRD) in the United Kingdom to identify patients diagnosed with breast cancer and treated with aromatase inhibitors or tamoxifen. CPRD is a primary care database and provided robust data in addressing our study question.
"First, general practitioners in United Kingdom are involved in long-term management of patients diagnosed with breast cancer. In addition, health care in United Kingdom is provided universally by the National Health Service. Thus, the continuity of data in UK CPRD provides for an ideal data source to examine long-term safety of aromatase inhibitors and tamoxifen.
"Using this data source, we identified 30,140 women who were at least 50 years of age and initiated treatment with aromatase inhibitors or tamoxifen. We followed the patients until either diagnosis of Parkinson's disease, loss to follow-up, or end of the study period. To account for differences between patients' characteristics, we used robust statistical methods to account for over 30 potential confounders, including demographic and lifestyle variables, comorbidities, prior treatments with prescription drugs, and markers of health care resource utilization."
3 Are these findings conclusive-and what are the clinical implications?
"We assessed the potential for numerous sources of biases that may present themselves in observational studies. These sensitivity analyses included assessing the potential for exposure and outcome misclassification, informative loss to follow-up, and missing data. Overall, we found consistent results across all these analyses which supported the robustness of our findings.
"It is possible that there is a differential risk of Parkinson's disease when comparing these drugs in certain subgroups of patients, such as older patients diagnosed with breast cancer. Additional large-scale, real-world evidence studies will be required to address these questions.
"Overall, this comparative safety study in a setting of clinical practice indicates that aromatase inhibitors, in comparison with tamoxifen, are not associated with increased risk of Parkinson's disease. This study adds to the long-term safety profile of aromatase inhibitors and provides physicians and patients with reassurance regarding the risk of Parkinson's disease with aromatase inhibitors compared with tamoxifen in management of postmenopausal women diagnosed with nonmetastatic breast cancer."