Aromatase Inhibitors and VTE/PE Risk
Aromatase inhibitors (AIs) are associated with a significantly lower risk of venous thromboembolism (VTE) and pulmonary embolism (PE) compared to tamoxifen in breast cancer patients. 1, 2
Risk Profile of Aromatase Inhibitors vs. Tamoxifen
Aromatase inhibitors demonstrate a more favorable thromboembolic risk profile than tamoxifen, which is a key safety advantage in the treatment of hormone receptor-positive breast cancer.
According to the European Society of Cardiology guidelines, in patients with breast cancer under hormonal therapy, higher rates of VTE are reported under tamoxifen compared with aromatase inhibitors 1
A large prospective cohort study of 12,904 postmenopausal women with hormone-receptor-positive breast cancer found that AI use was associated with at least 41% lower VTE risk compared with tamoxifen use (adjusted HR 0.59,95% CI 0.43,0.81) 2
The FDA label for anastrozole specifically notes that "patients receiving anastrozole had a lower incidence of venous thromboembolic events compared with patients receiving tamoxifen" 3
Comparative VTE Risk Among Aromatase Inhibitors
While all AIs have lower VTE risk than tamoxifen, there may be subtle differences between individual AIs:
A network meta-analysis comparing the cardiovascular safety profiles of the three main AIs found that the total cardiovascular risk ranking is letrozole, exemestane, and anastrozole in descending order (with anastrozole having the most favorable profile) 4
However, specific VTE risk differences between individual AIs are not clearly established in the literature, and all three (anastrozole, letrozole, and exemestane) are generally considered to have similar thromboembolic risk profiles
Absolute Risk of VTE/PE with Aromatase Inhibitors
Despite having lower risk than tamoxifen, AIs may still carry some VTE risk:
In the MAP.3 trial evaluating exemestane for breast cancer prevention, the incidence of VTE was 11 events in the exemestane group versus 7 events in the placebo group, though this difference was not statistically significant 1
Case reports have documented instances of pulmonary emboli occurring in patients on aromatase inhibitor therapy, suggesting that while the risk is lower than with tamoxifen, it is not zero 5
The crude rates of DVT and PE in breast cancer patients on hormonal therapy were reported as 4.6 and 2.8 per 1000 person-years, respectively 2
Clinical Implications and Management
When considering AIs for breast cancer treatment:
Cardiovascular risk factors should be assessed and managed before initiating therapy, particularly in patients with pre-existing risk factors for thromboembolism
For patients with high thromboembolic risk, anastrozole may be the preferred AI based on its more favorable cardiovascular safety profile 4
Regular monitoring for signs and symptoms of VTE/PE is recommended, particularly in patients with additional risk factors such as advanced age, obesity, prior history of VTE, or immobility
The risk of VTE/PE should be weighed against the benefits of AI therapy in reducing breast cancer recurrence, with the understanding that AIs generally present a more favorable thromboembolic risk profile than tamoxifen
Key Risk Factors for VTE in Cancer Patients
Patients on AIs should be monitored more closely for VTE if they have additional risk factors:
- Cancer-related factors: advanced stage, pancreatic/brain/stomach/kidney/lung primary sites
- Patient-related factors: older age, female sex, African ethnicity, comorbidities, prior VTE history
- Treatment-related factors: recent surgery, hospitalization, central venous catheter use 1
In summary, while aromatase inhibitors carry a lower risk of VTE/PE compared to tamoxifen, clinicians should remain vigilant for thromboembolic events, particularly in patients with additional risk factors for thrombosis.