Abstract P3-12-04: Efficacy of extended adjuvant aromatase inhibitors in subgroups of women with early breast cancer
Authors: H Goldvaser, I Algorashi, D Ribnikar, H Majeed, A Ocana, B Seruga, AJ Templeton, E Amir
Journal: Cancer Research (2018)

Abstract Background: Randomized trials (RCTs) have reported improvements in breast cancer outcomes from extending treatment with aromatase inhibitors (AIs) beyond the initial 5 years after diagnosis. It is uncertain whether this effect is consistent in different subgroups. Methods: We identified RCTs that compared extended AIs to placebo or no treatment using a systematic search of MEDLINE. The search was supplemented by a review of abstracts from the American Society of Clinical Oncology and San Antonio Breast Cancer Symposium meetings between 2013 and 2016. Hazard ratios (HRs) and 95% confidence intervals (CI) for disease-free survival (DFS) were extracted or estimated from forest plots and included in a meta-analysis using generic inverse variance and random effects modelling. Pre-specified subgroups included age (&amp;lt;60 ± 5 years vs. ≥60 ± 5 years), tumor size (≤2 cm vs. &amp;gt;2 cm), nodal status (positive vs. negative), hormone receptor status (estrogen [ER] and progesterone receptor [PR] positive vs. ER or PR positive) and administration of adjuvant chemotherapy (yes vs. no). Results: Seven trials comprising 16,349 patients were analyzed. Studies designs and prior endocrine therapy are shown in Table 1 Table 1: Characteristics of included studies.TrialTreatment ArmsSample sizePrior endocrine treatmentABCSG 6aAnastrozole 3 years vs. none387/ 469Tamoxifen± aminoglutethimide: 100%, 5 yearsMA 17Letrozole 5 years vs. placebo2572/ 2577Tamoxifen: 100%, ∼5 yearsNSABP B-33Exemestane 5 years vs. placebo783/ 779Tamoxifen: 100%, ∼5 yearsDutch DATAAnastrozole 6 years vs,. anastrozole 3 years827/ 833Tamoxifen: 100%, 2-3 yearsIDEALLetrozole 5 years vs. letrozole 2.5 years903/ 898Any endocrine treatment (tamoxifen/AIs/sequence of tamoxifen+ AIs): 100%, 5 yearsMA.17RLetrozole 5 years vs. placebo959/ 959AIs: 100%, ∼5 years Prior tamoxifen: 79.3%NSABP B-42Letrozole 5 years vs. placebo1959/ 1964Any endocrine treatment (AIs/sequence of tamoxifen+ AIs): 100%, 5 years . The pooled effect of prolonged treatment with AIs in different subgroups is shown in the Table 2. Table 2: Intra-subgroup comparison of longer AIs treatment effect by subgroupsSubgroup ASubgroup BHR (95% CI) Subgroup AHR (95% CI) Subgroup BP for differenceAge &amp;lt;60 ± 5Age ≥60 ± 50.83 (0.70-0.99)0.85 (0.74-0.97)0.64T &amp;gt;2 cmT ≤2 cm0.77 (0.55-1.06)0.88 (0.68-1.13)0.44N positiveN negative0.72 (0.63-0.83)0.83 (0.64-1.08)0.22ER and PR positiveER or PR positive0.68 (0.44-1.04)1.03 (0.53-2.02)0.27Adjuvant chemotherapyNone0.71 (0.59-0.86)0.80 (0.65-0.98)0.51 Overall, the effect of prolonged AIs was similar in all subgroups. However, non-significantly greater effect sizes were seen in patient with larger tumors, nodal involvement, presence of both ER and PR expression and those treated with adjuvant chemotherapy. Conclusions: Extended treatment with adjuvant AIs is associated with similar relative improvements in DFS in all subgroups analyzed. The greater effect size seen in node positive and large tumor subgroups and the higher baseline risk of recurrence will likely translate to a higher absolute benefit from extended AIs in these groups. Citation Format: Goldvaser H, Algorashi I, Ribnikar D, Majeed H, Ocana A, Seruga B, Templeton AJ, Amir E. Efficacy of extended adjuvant aromatase inhibitors in subgroups of women with early breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-12-04.