The efficacy of neoadjuvant chemotherapy was lower than expected for patients with estrogen receptor (ER)-positive primary breast cancer exhibiting high levels of Ki67 after 2 to 4 weeks of neoadjuvant aromatase inhibitor therapy (AI), according to a study published in the Journal of Clinical Oncology.1
To evaluate Ki67 as a tool for chemotherapy decisions during and after neoadjuvant aromatase inhibitor therapy of breast cancer, researchers assessed the pathologic complete response rate of women with ER-positive primary breast cancer triaged to chemotherapy when the Ki67 level was greater than 10% after AI treatment.
For the open-label, phase 3 American College of Surgeons Oncology Group (ACOSOG) Z1031B trial (ClinicalTrials.gov Identifier: NCT00265759), researchers enrolled postmenopausal women with stage II or III ER-positive breast cancer and randomly assigned them to receive neoadjuvant AI therapy with anastrozole, exemestane, or letrozole.
If Ki67 level was greater than 10% after 2 to 4 weeks of an AI, patients were switched to neoadjuvant chemotherapy. Investigators defined the efficacy threshold as a pathologic complete response rate of greater than 20%.
Only 5.7% (95% CI, 0.7-19.1) of the 35 patients who were switched to neoadjuvant chemotherapy achieved a pathologic complete response.
Researchers also assessed whether time to recurrence differed by Ki67-based Preoperative Endocrine Prognostic Index (PEPI) score. Patients with T1 or T2, N0, Ki67 less than 2.7%, and an Allred score greater than 2 had a PEPI score of 0.
Median follow-up was 5.5 years; patients with a PEPI score of 0 had a 73% lower risk of recurrence compared with those with a PEPI score greater than 0 (hazard ratio, 0.27; 95% CI, 0.092-0.764; P = .014). Nearly 4% of the 109 patients with a PEPI score of 0 relapsed vs 14.4% of the 341 patients with a PEPI score greater than 0.
These findings support the investigation of adjuvant endocrine monotherapy in this subpopulation.
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Researchers are studying both the Ki67 proliferation index and the PEPI score approach in the phase 3 ALTERNATE study (ClinicalTrials.gov Identifier: NCT01953588), which is comparing the efficacy of neoadjuvant fulvestrant with the combination of fulvestrant plus anastrozole among postmenopausal women with stage II or III ER-positive breast cancer.
- Ellis MJ, Suman VJ, Hoog J, et al. Ki67 proliferation index as a tool for chemotherapy decisions during and after neoadjuvant aromatase inhibitor treatment of breast cancer: Results from the American College of Surgeons Oncology Group Z1031 Trial (Alliance). J Clin Oncol. 2017 Jan 3. doi: 10.1200/JCO.2016.69.4406 [Epub ahead of print]