Breast cancer (BC) can occur in 40% of women 5 to 20 years postdiagnosis despite the use of 5 years of adjuvant endocrine therapy (ET). There is much debate about the adequate length of treatment with ET in postmenopausal women, although a minimum duration of 5 years is recommended in patients with resected BC.

To examine this issue further, a network meta-analysis (NMA) was preferred using data gathered from a comprehensive search on MEDLINE, Embase, and Cochrane Central Register of Controlled Trials. NMA is a technique used for comparing >3 interventions simultaneously in a single analysis by combining both direct and indirect evidence across a network of studies. The purpose of this NMA was to compare all studies on extended therapy beyond 5 years of aromatase inhibitor (AI) therapy and to ascertain the optimal duration of extended ET in resected BC in postmenopausal women.

This NMA included randomized phase III trials; trials that compared different durations or extended with no-extended adjuvant ET in postmenopausal ER+/HERS-negative early BC after an initial course of any approved ET (e.g., tamoxifen followed by an AI or AI monotherapy); trials that reported the intention-to-treat population’s overall survival (OS) and/or disease-free survival (DFS) and hazard ratios (HRs); and were in English. Exclusion criteria included studies in which ET+ luteinizing hormone-releasing hormone analogues or experimental agents, such as cyclin-dependent kinase 4/6 inhibitors or anti-human epidermal growth factor receptor 2 (HER2) agents, were employed; previous versions of the same trial; and studies for which full-text articles were not available.

The primary outcome of the study was DFS, and the secondary outcome was OS. Patients with node-positive versus node-negative disease were studied in a subgroup analysis. Treatment regimens were ranked using estimated surface under the cumulative ranking curve (SUCRA) P scores. SUCRA represents the percentage of efficacy achieved by an agent compared with an ideal imaginary agent without uncertainty. The highest and lowest P scores indicated the best and worse treatment options, respectively. The investigators also analyzed the data based on disease stage, initial ET therapy, histological grade, and use of chemotherapy.

Twelve studies were included in the NMA. Investigators found that DFS was improved by 23% when ET was extended for an additional 2 to 3 years after the initial 5 years compared with no extension of therapy (HR = .77; 95% CI, 0.69-87). Similar results were found with 5 years of extension with an AI compared with a duration of 2 to 3 years of extension (HR = .75; 95% CI, 0.69-0.82). The benefit of increasing ET to 3 to 4 years was negligible when compared with no extension in the overall group. Over a 10-year period, intermittent versus continuous administration of letrozole demonstrated similar efficacy. Examination of SUCRA scores found that 5 years followed by 2 to 3 years of AI treatment represented the best and second-best drug treatment options, respectively. There was no significant difference in DFS associated with extending ET 5 more years for a total of 10 years compared with 2 to 3 years (HR = .97; 95% CI, 0.88-1.08) of treatment or 3 to 4 years (HR = .87, 95% CI, 0.72-1.06) of therapy.

However, in women with node-positive BC, 5 years of ET therapy was the most effective treatment option and was recommended over no extension (HR = 0.75; 95% CI, 0.67-0.84) or 2 to 3 more years (HR = .86; 95% CI, 0.75-0.99) of ET. In node-negative BC, both 2 to 3 years and 5 years of extended ET increased DFS to a similar extent compared with no extension, with a duration of 2 to 3 years (HR = .93; 95% CI, 0.83-1.1) producing the most favorable SUCRA scores. Extended duration of ET beyond the initial 5 years did not improve OS, with 2 to 3 years of therapy producing the highest SUCRA scores followed by 3 to 4 years of treatment. There was no difference in outcome in an additional 2 to 3 years of therapy compared with 5 years of therapy (HR = .92; 95% CI, 0.8-1.6).

There was an interesting relationship observed between tamoxifen and AI use such that with the longer duration of tamoxifen use, the greater the potential benefit of additional years of receiving an AI, with substantial advantages seen in the 5-year and 2- to 3-year arms.

This study is useful for pharmacists as it helps to clarify the recommended length of treatment of ET in postmenopausal BC women and can be used in shared decision-making.

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