Randomized phase II neoadjuvant comparison between letrozole, anastrozole, and exemestane for postmenopausal women with estrogen receptor-rich stage 2 to 3 breast cancer: Clinical and biomarker outcomes and predictive value of the baseline PAM50-based intrinsic subtype--ACOSOG Z1031 Full Text
Journal of Clinical Oncology, 05/13/2011
Clinical Article
Ellis MJ et al. – Neoadjuvant AI treatment markedly improved surgical outcomes. Ki67 and PEPI data demonstrated that the three agents tested are biologically equivalent and therefore likely to have similar adjuvant activities. LumA tumors were more likely to have favorable biomarker characteristics after treatment; however, occasional paradoxical increases in Ki67 (12% of tumors with > 5% increase after therapy) suggest treatment-resistant cells, present in some LumA tumors, can be detected by post-treatment profiling.
Methods- 377 postmenopausal women with clinical stage II to III ER-positive (Allred score 6-8) breast cancer randomly assigned to receive neoadjuvant exemestane, letrozole, or anastrozole
- Primary end point was clinical response
- Secondary end points included BCS, Ki67 proliferation marker changes, Preoperative Endocrine Prognostic Index (PEPI), and PAM50-based intrinsic subtype analysis
- On the basis of clinical response rates, letrozole and anastrozole were selected for further investigation; however, no other differences in surgical outcome, PEPI score, or Ki67 suppression were detected
- BCS rate for mastectomy-only patients at presentation 51%
- PAM50 analysis identified AI-unresponsive nonluminal subtypes (human epidermal growth factor receptor 2 enriched or basal-like) in 3.3% of patients
- Clinical response and surgical outcomes similar in luminal A (LumA) versus luminal B tumors; however, a PEPI of 0 (best prognostic group) highest in LumA subset (27.1% v 10.7%; P = .004)
