The expert panel completed an update of the ASCO clinical practice guideline for adjuvant endocrine therapy based on new data on optimal treatment duration, which focuses on recommendations for adjuvant tamoxifen therapy. ASCO formed an update committee to conduct a systematic review of randomized clinical trials from January 2009 to June 2013 and to analyze the results of three historical trials. The committee made guideline recommendation updates based on a review of the evidence synthesis. Meaningful outcomes included survival, disease recurrence, and adverse events. This guideline update reflects the most recent data on the duration of tamoxifen treatment, for which there are now five studies of tamoxifen treatment beyond 5 years. The two largest studies with the longest follow-up showed a survival advantage for 10 years of tamoxifen treatment for breast cancer. In addition to a modest survival advantage, extending treatment to 10 years provides benefits such as lower rates of breast cancer recurrence and risk of contralateral breast cancer compared to 5 years of tamoxifen treatment. Based on reported results, previous ASCO guidelines recommended 5 years of treatment with tamoxifen for premenopausal women with hormone receptor-positive breast cancer and at least 5 years of adjuvant aromatase inhibitor or tamoxifen sequential aromatase inhibitor treatment for postmenopausal patients. If premenopausal or postmenopausal women have been on adjuvant tamoxifen therapy for 5 years, they will have continued tamoxifen therapy for a total of 10 years. If postmenopausal women have been on adjuvant tamoxifen therapy for 5 years, they may continue tamoxifen therapy or switch to adjuvant endocrine therapy with an aromatase inhibitor for 10 years. Clinical Question 1A: Which adjuvant endocrine therapy is indicated for postmenopausal women with hormone receptor-positive breast cancer? Recommendation 1A: The Update Committee recommends that, based on data from randomized controlled trials, most postmenopausal women may consider AI for use during adjuvant therapy to reduce the risk of recurrence, with similar results in prospective studies, either as primary therapy or after 2 to 3 years of tamoxifen therapy. the duration of AI therapy should not exceed 5 years. Clinical Question 1B: What is the appropriate duration of adjuvant endocrine therapy? Recommendation 1B: AI therapy should not exceed 5 years, either for primary adjuvant therapy or for extended adjuvant therapy, except in clinical trials. In terms of treatment procedures, the Update Committee recommends that patients receiving 2 or 3 years of tamoxifen therapy be treated with AI for a total of 5 years of adjuvant endocrine therapy based on the evidence from available randomized controlled trials. The update committee recommended that patients who discontinue treatment after less than 5 years of initial AI therapy may be considered for continued treatment with triamcinolone acetonide to complete a total of 5 years of adjuvant endocrine therapy. Clinical Question 1C: If tamoxifen is given first, how long before switching to AI therapy? Recommendation 1C: The Update Committee recommends that, based on the available evidence from randomized controlled trials, patients who are first treated with adjuvant tamoxifen may be switched to AI agents after 2 to 3 years (sequential therapy) or after 5 years (extended therapy). No optimal timing of the switch to tamoxifen therapy (or vice versa) can be derived from the available direct evidence as to when the greatest benefit from AI can be achieved. The update committee recommended switching treatment regimens after 2 to 3 years based on data from sequential treatment trials. Results from several extended adjuvant randomized trials support the strategy of switching treatment regimens after 5 years. Clinical Question 2: For specific patient populations, do AI therapy and tamoxifen therapy yield different benefits? Recommendation 2: Direct evidence from randomized trials does not identify a specific biomarker or clinical subset population from which adjuvant treatment strategies, tamoxifen or AI monotherapy or sequential therapy, may yield the best prognosis. For the male breast cancer patient population, tamoxifen is the standard adjuvant endocrine therapy. The update committee recommended against the use of CYP2D6 genotype status to select adjuvant endocrine therapy regimens. The Update Committee encourages the concurrent use of CYP2D6 inhibitors (e.g., bupropion or fluoxetine, paroxetine; Table 5) and tamoxifen because of the known interactions that can occur between them. Clinical Question 3: What are the toxicity and risks of adjuvant endocrine therapy? Recommendation 3: The Update Committee recommends that clinicians consider adverse events, patient preferences, and clinical status when making decisions about adjuvant endocrine therapy for postmenopausal women. Clinicians should weigh adverse events when faced with multiple treatment options. The Update Committee recommends that treatment regimens be changed when patients experience intolerable adverse events with continued treatment. Clinical Question 4: Are AIs an effective adjuvant treatment for women with premenopausal diagnosis of breast cancer? Recommendation 4: The Update Committee recommends 5 years of tamoxifen therapy for women with premenopausal and perimenopausal diagnoses of breast cancer. Other considerations: The Update Committee recommends that clinicians carefully assess the menopausal status of patients with premenopausal and perimenopausal diagnoses of breast cancer. Clarifying menopausal status can be challenging. Even for women who have not had menstruation for more than 1 year, laboratory testing alone is not sufficient, as the patient’s ovarian function may return. This applies especially to those patients with amenorrhea caused by chemotherapy or tamoxifen treatment. Clinical Question 5: Can third-generation AIs be used interchangeably? Recommendation 5: There is a lack of directly comparable data, and the Update Committee suggests a “class effect” of benefit from AI therapy based on validated data. The question of whether there are meaningful clinical differences between commercially available third-generation AIs is not yet on the agenda. The update committee’s clinical opinion (rather than direct evidence from randomized trials) is that postmenopausal patients who cannot tolerate a particular AI drug and remain on adjuvant endocrine therapy are advised to consider triamcinolone acetonide or other AI.