Triage to chemotherapy using a Ki67-based Preoperative Endocrine Prognostic Index (PEPI), which also integrates residual disease burden, appears useful for deescalating adjuvant treatment after neoadjuvant aromatase inhibitor (AI) therapy for breast cancer, investigators report in the Journal of Clinical Oncology.

Only 4 of 109 patients (3.7%) in the American College of Surgeons Oncology Group Z1031B trial with a PEPI score of 0 relapsed after a median of 5.5 years (and were therefore unlikely to benefit from adjuvant chemotherapy), compared with 49 (14.4%) of 341 patients with a PEPI score greater than 0 (recurrence hazard ratio, 0.27), reported Matthew J. Ellis, MD , of Baylor College of Medicine, Houston, and his associates.

However, only 2 of 35 patients (5.7%) in the randomized phase II trial who were switched from AI to neoadjuvant chemotherapy because of Ki67 level greater than 10% after 2-4 weeks experienced pathologic complete response (pCR), Dr. Ellis and associates said.

“The low pCR rate for ACOSOG Z1031B patients who switched to neoadjuvant chemotherapy contradicts the hypothesis that AI-resistant proliferation in ER-rich tumors is associated with enhanced chemotherapy response,” they said (J Clin Oncol. 2016 Jan 3. doi: 10.1200/JCO.2016.69.4406 ).

Study subjects were postmenopausal women with stage II or III ER+ breast cancer who were randomly assigned to receive neoadjuvant AI therapy with anastrozole, exemestane, or letrozole, then triaged to neoadjuvant chemotherapy based on Ki67 level. The efficacy of chemotherapy was lower than expected in this population, suggesting that optimal therapy for intrinsically AI-resistant disease – which will “likely depend on new insights into the molecular basis for primary endocrine therapy resistance”– should be further investigated, they wrote, noting that the triage approaches used in this study are being evaluated in the ongoing phase III ALTERNATE trial .

Dr. Ellis disclosed financial and other relationships with Bioclassifier, Novartis, Pfizer, Celgene, AstraZeneca, NanoString Technologies, and Prosigna.