Exemestane and letrozole are medications prescribed for the treatment of certain types of breast cancer. These drugs fall under a class known as aromatase inhibitors, a form of hormone therapy. Their purpose is to manage hormone-sensitive cancers, particularly in postmenopausal women.
How Aromatase Inhibitors Work
Aromatase inhibitors target the aromatase enzyme, which converts androgens (male hormones) into estrogens (female hormones) in the body. In postmenopausal women, ovaries no longer produce estrogen, and peripheral tissues, such as fat, become the primary site for estrogen production through this enzyme.
By blocking the aromatase enzyme, these medications reduce estrogen levels in the body. This reduction is important for hormone receptor-positive breast cancers, as their growth is often stimulated by estrogen. Lowering estrogen starves these cancer cells, slowing or stopping their proliferation. This mechanism differs from other hormone therapies, like tamoxifen, which block estrogen receptors on cancer cells rather than reducing estrogen production itself.
Distinctions Between Exemestane and Letrozole
Exemestane and letrozole, while both aromatase inhibitors, differ in their chemical structure and how they interact with the aromatase enzyme. Exemestane is classified as a steroidal aromatase inactivator, with a structure similar to the enzyme’s natural substrate, androstenedione. It binds irreversibly to the aromatase enzyme, destroying it through “suicide inhibition.” This results in sustained estrogen reduction.
Letrozole is a non-steroidal aromatase inhibitor. It is a triazole derivative binding reversibly to the heme component of the aromatase enzyme. This reversible binding inhibits the enzyme’s ability to convert androgens into estrogens. The enzyme is not permanently inactivated. Both are highly potent, with third-generation inhibitors like exemestane and letrozole achieving over 98% inhibition of aromatase activity.
These differences can have clinical implications. Exemestane has shown activity in patients whose disease has progressed after treatment with non-steroidal aromatase inhibitors like letrozole, suggesting a lack of cross-resistance. All three third-generation aromatase inhibitors (anastrozole, letrozole, and exemestane) are effective for hormone-sensitive breast cancer, though some evidence suggests letrozole may be the most potent non-steroidal option for estrogen suppression. Exemestane is approved for adjuvant treatment in postmenopausal women with early breast cancer, either as initial monotherapy or as a switch therapy after 2-3 years of tamoxifen.
Managing Potential Side Effects
Aromatase inhibitors, by lowering estrogen levels, often cause menopausal-like side effects. Hot flashes are a frequently reported side effect for both exemestane and letrozole, affecting 24% to 13% of users, respectively. Joint pain is another common complaint, reported by 31% of exemestane users and 22% of letrozole users. Other shared side effects include fatigue, muscle pain, and weight gain.
Reduced estrogen also links aromatase inhibitor use to bone density issues, such as osteopenia and osteoporosis. Patients may experience vaginal dryness or irritation. Exemestane may have a lower risk of bone loss and high cholesterol levels compared to other aromatase inhibitors. Patients should discuss side effects with their healthcare provider, as management strategies can alleviate symptoms and support treatment adherence.
Factors Influencing Treatment Choice
Selecting between exemestane and letrozole is a personalized decision made in consultation with a medical professional. Healthcare providers consider factors including the patient’s medical history, prior cancer treatments, and existing health conditions. Cancer characteristics, such as hormone receptor status and stage, also play a significant role.
Patient tolerance to side effects is another important consideration. While both drugs have similar side effect profiles, individual responses vary, and some patients may tolerate one better. If a patient experiences significant adverse effects from one aromatase inhibitor, their specialist might recommend switching. Ultimately, the goal is to select the most effective and tolerable treatment plan for each individual.