Disappointing Efficacy of Chemotherapy Guided by Ki67 Level After Neoadjuvant AI Therapy for Breast Cancer

Key Points

  • The pathologic complete response rate was low in patients with estrogen receptor–positive primary breast cancer who were switched to chemotherapy on the basis of Ki67 level > 10%.
  • The relapse rate was significantly lower among patients with a PEPI score of 0 vs those with a PEPI score > 0.

In an analysis in the American College of Surgeons Oncology Group (ACOSOG) Z1031 Trial/Alliance reported in the Journal of Clinical Oncology, Ellis et al found that switching to chemotherapy in patients with elevated Ki67 levels after 2 to 4 weeks of neoadjuvant aromatase inhibitor therapy resulted in a low pathologic complete response rate in estrogen receptor–positive primary breast cancer.

Study Details

In the trial, postmenopausal women with stage II or III estrogen receptor–positive (Allred score = 6–8) breast cancer were randomized to receive neoadjuvant aromatase inhibitor therapy with anastrozole, exemestane, or letrozole. In a protocol amendment (ACOSOG Z1031B), patients were switched to neoadjuvant chemotherapy if tumor Ki67 assessment after 2 to 4 weeks of aromatase inhibitor showed a Ki67 level > 10%. The predefined efficacy threshold was a pathologic complete response rate > 20%. The Ki67-based Preoperative Endocrine Prognostic Index (PEPI) score was used to determine whether time to recurrence in patients completing neoadjuvant aromatase inhibitor differed by PEPI = 0 (T1 or T2, N0, Ki67 < 2.7%, estrogen receptor Allred > 2) vs PEPI > 0 disease.

Outcomes by Ki67 Status

Among 35 patients switched to neoadjuvant chemotherapy, pathologic complete response rate was observed in 2 patients (5.7%, 95% confidence interval = 0.7%–19.1%). After a median follow-up of 5.5 years in patients completing neoadjuvant aromatase inhibitor treatment, relapse had occurred in 4 of 109 patients (3.7%) with a PEPI score of 0 vs 49 of 341 patients (14.4%) with a PEPI score > 0 (hazard ratio = 0.27, P = .014).

The investigators concluded: “Chemotherapy efficacy was lower than expected in [estrogen receptor–]positive tumors exhibiting [aromatase inhibitor–]resistant proliferation. The optimal therapy for these patients should be further investigated. For patients with PEPI = 0 disease, the relapse risk over 5 years was only 3.6% without chemotherapy, supporting the study of adjuvant endocrine monotherapy in this group. These Ki67 and PEPI triage approaches are being definitively studied in the ALTERNATE trial (NCT01953588).”

The study was supported by National Cancer Institute grants, the Breast Cancer Research Foundation, and a Komen St. Louis Affiliate Clinical Trials grant.

Matthew J. Ellis, MB, BChir, PhD, of Baylor College of Medicine, is the corresponding author of the Journal of Clinical Oncology article. Dr. Ellis and Vera J. Suman, PhD, of Mayo Clinic, Rochester, are joint first authors.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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