Exemestane and anastrozole are two commonly prescribed medications for postmenopausal women diagnosed with hormone receptor-positive (HR+) breast cancer. These drugs belong to a class of medicines known as aromatase inhibitors. They are employed to reduce the risk of cancer recurrence and manage advanced disease. This article explores how these two treatments work, their effectiveness, differing side effect profiles, and the considerations involved in selecting one for a patient.
How Exemestane and Anastrozole Work
Aromatase inhibitors function by targeting the aromatase enzyme, which converts androgens into estrogens. In postmenopausal women, the ovaries no longer produce significant amounts of estrogen. Instead, the primary source of circulating estrogen comes from this conversion process occurring in peripheral tissues like fat, muscle, and the breast. By blocking the aromatase enzyme, these medications significantly lower estrogen levels, thereby depriving estrogen-dependent breast cancer cells of the hormone needed for their growth.
Anastrozole is a non-steroidal aromatase inhibitor. It works by reversibly binding to the aromatase enzyme, temporarily interfering with its ability to produce estrogen. This binding is competitive, meaning anastrozole competes with the natural androgen substrates for the enzyme’s active site.
Exemestane operates differently as a steroidal aromatase inhibitor. It is structurally similar to androstenedione, a natural substrate of the aromatase enzyme. Exemestane acts as a “false substrate,” undergoing processing by the enzyme to form an intermediate that then binds irreversibly to the enzyme’s active site. This permanent inactivation, often termed “suicide inhibition,” leads to the destruction of the aromatase enzyme and a sustained reduction in estrogen production.
Comparing Clinical Efficacy
Clinical trials have evaluated the effectiveness of both exemestane and anastrozole in treating hormone receptor-positive breast cancer. These studies aim to determine their impact on preventing cancer recurrence and improving patient survival rates. Researchers have conducted large-scale randomized trials, sometimes comparing these two drugs directly or against other established treatments like tamoxifen.
The NCIC CTG MA.27 trial directly compared five years of exemestane with five years of anastrozole in postmenopausal women with early breast cancer. This phase III trial involving over 7,500 women found similar event-free survival rates for both drugs at a median follow-up of 4.1 years. The 4-year event-free survival was approximately 91% for exemestane and 91.2% for anastrozole, indicating comparable effectiveness in preventing recurrence.
Overall survival, distant disease-free survival, and the incidence of new primary contralateral breast cancer were found to be similar between the two treatments in this trial. Other studies investigating advanced breast cancer have indicated that the efficacy and safety profiles of exemestane are comparable to those of anastrozole. While initial hypotheses suggested exemestane might offer superior efficacy due to its irreversible mechanism, clinical data support that both drugs provide similar treatment outcomes for patients.
Contrasting Side Effect Profiles
While both exemestane and anastrozole effectively lower estrogen levels, they share common side effects experienced by patients. These adverse effects include hot flashes, joint pain, and fatigue, which are largely attributable to the significant reduction in estrogen. These symptoms can be challenging for patients to manage, impacting their quality of life during treatment.
Beyond these shared effects, differences emerge in their impact on bone mineral density and blood lipid profiles. Aromatase inhibitors accelerate bone thinning, increasing the risk of osteoporosis and fractures. However, research suggests that exemestane may have a less detrimental effect on bone density compared to non-steroidal aromatase inhibitors like anastrozole. A companion analysis of the MA.27 trial observed that patients on exemestane reported fewer new cases of osteopenia or osteoporosis than those on anastrozole, although the mean change in bone mineral density at specific sites did not always differ significantly.
Regarding blood lipid profiles, evidence indicates that exemestane might have a more favorable impact on cholesterol levels compared to anastrozole. This difference could be relevant for patients with pre-existing cardiovascular concerns. However, the clinical significance of these differences can vary, and analyses suggest that both drugs may comparably affect bone mineral density and lipid profiles, or that the differences are not always statistically significant.
Choosing Between Exemestane and Anastrozole
The decision to prescribe either exemestane or anastrozole is individualized, reflecting the needs and health profile of each patient. Oncologists consider factors beyond the comparable efficacy of these two aromatase inhibitors. A patient’s existing medical conditions play a role in this approach.
A patient with a history of osteoporosis or a higher risk of bone fractures might be considered for exemestane, given evidence suggesting a less adverse effect on bone mineral density. Conversely, if a patient has pre-existing cardiovascular disease or elevated cholesterol levels, the physician might weigh the effects of each drug on lipid profiles. Tolerance to specific side effects is an important consideration; if a patient experiences intolerable side effects with one drug, switching to the other might be recommended to improve their comfort and adherence to therapy.
Practical aspects such as insurance coverage and medication cost can influence the choice, as these can impact a patient’s ability to access and afford their prescribed treatment. There is no universally “better” drug between exemestane and anastrozole. Instead, the selection aims to find the “better fit” for an individual patient, balancing their cancer treatment needs with their overall health, personal preferences, and practical circumstances to ensure optimal outcomes.