There are currently three FDA-approved aromatase inhibitors (AIs) indicated for adjuvant treatment of breast cancer (BC) in postmenopausal women: letrozole, anastrozole, and exemestane. The American Society of Clinical Oncology recently updated its clinical practice guidelines on adjuvant endocrine therapy for postmenopausal women with hormone receptor–positive (HR+) BC.

These guidelines had previously been revised in 2016, but new, relevant information has become available since then. This update is based on results of six randomized phase III clinical trials published between 2012 and 2018 that analyzed the optimal duration of AI treatment in postmenopausal women with Stage I to III HR+ BC who were receiving these drugs for more than 5 years as part of an extended adjuvant endocrine regimen. Four of the six studies examined the effects of letrozole, and two studies evaluated the use of anastrozole in this population; no study evaluated exemestane. In at least five of the six studies, participants had received prior adjuvant tamoxifen therapy.

While an increase in overall survival was not seen with the use of extended AIs, their use was associated with a significantly reduced risk of BC recurrence and contralateral BC compared with the placebo group. However, bone-related adverse effects (i.e., osteoporosis, fracture) and a trend toward an increased risk of arterial thrombotic events were more common in the treatment groups.

This focused reevaluation resulted in five recommendations based on the presence of node-positive/negative disease: 1) For node-negative BC patients, the use of extended AI therapy for up to 10 years should be based on an assessment of established prognostic factors for recurrence risk. Consideration should be made on a case-by-case basis (higher risk, node-negative stage T2/T3 tumor, and T1c tumor with higher risk prognostic factors vs. T1a/T1b tumor or T1c tumor with lower risk prognostic factors vs. low risk, T1ab tumor) because although many women may benefit from extended therapy, it is not recommended for all women with low-risk, node-negative BC since they are at reduced risk of recurrence. 2) For women with node-positive BC, AI therapy should be continued for up to 10 years. 3) For women on extended AI therapy, 10 years should be the maximum duration of therapy. 4) For the prevention of secondary or contralateral BC, which is a major benefit of extended AI therapy, the risk for developing second BCs and the need for extended therapy should be evaluated in the context of prior treatments employed. 5) For women using or contemplating extended AI adjuvant treatment, this decision should be part of a shared process between the clinical team and the patient, with all involved weighing the risks and benefits of prolonged treatment. Longer duration of AI use was associated with increased cardiovascular events, bone fractures, and treatment discontinuation secondary to adverse drug events.

When extended adjuvant hormonal therapy is indicated, any of the following regimens may be utilized: AI for up to a total of 10 years; tamoxifen for 2 to 3 years followed by AI for 7 to 8 years; tamoxifen for 5 years followed by AI for 5 years; or tamoxifen for 10 years. Relative benefits for extended adjuvant endocrine therapy were greater in women who switched from tamoxifen to AIs.

Less benefit may be seen among women who continue tamoxifen for 10 years or who are treated with AIs in the first 5 years and then continue on AI therapy. Although AI therapy is recommended during the course of adjuvant endocrine therapy, if a patient is intolerant to AIs, does not want to take AIs, or is premenopausal, the use of tamoxifen is recommended.

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