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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).

Publication ,  Journal Article
Ellis, MJ; Suman, VJ; Hoog, J; Goncalves, R; Sanati, S; Creighton, CJ; DeSchryver, K; Crouch, E; Brink, A; Watson, M; Luo, J; Tao, Y; Ma, CX ...
Published in: J Clin Oncol
April 1, 2017

Purpose To determine the pathologic complete response (pCR) rate in estrogen receptor (ER) -positive primary breast cancer triaged to chemotherapy when the protein encoded by the MKI67 gene (Ki67) level was > 10% after 2 to 4 weeks of neoadjuvant aromatase inhibitor (AI) therapy. A second objective was to examine risk of relapse using the Ki67-based Preoperative Endocrine Prognostic Index (PEPI). Methods The American College of Surgeons Oncology Group (ACOSOG) Z1031A trial enrolled postmenopausal women with stage II or III ER-positive (Allred score, 6 to 8) breast cancer whose treatment was randomly assigned to neoadjuvant AI therapy with anastrozole, exemestane, or letrozole. For the trial ACOSOG Z1031B, the protocol was amended to include a tumor Ki67 determination after 2 to 4 weeks of AI. If the Ki67 was > 10%, patients were switched to neoadjuvant chemotherapy. A pCR rate of > 20% was the predefined efficacy threshold. In patients who completed neoadjuvant AI, stratified Cox modeling was used to assess whether time to recurrence differed by PEPI = 0 score (T1 or T2, N0, Ki67 < 2.7%, ER Allred > 2) versus PEPI > 0 disease. Results Only two of the 35 patients in ACOSOG Z1031B who were switched to neoadjuvant chemotherapy experienced a pCR (5.7%; 95% CI, 0.7% to 19.1%). After 5.5 years of median follow-up, four (3.7%) of the 109 patients with a PEPI = 0 score relapsed versus 49 (14.4%) of 341 of patients with PEPI > 0 (recurrence hazard ratio [PEPI = 0 v PEPI > 0], 0.27; P = .014; 95% CI, 0.092 to 0.764). Conclusion Chemotherapy efficacy was lower than expected in ER-positive tumors exhibiting AI-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 (Alternate Approaches for Clinical Stage II or III Estrogen Receptor Positive Breast Cancer Neoadjuvant Treatment in Postmenopausal Women: A Phase III Study; clinical trial information: NCT01953588).

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Published In

J Clin Oncol

DOI

EISSN

1527-7755

Publication Date

April 1, 2017

Volume

35

Issue

10

Start / End Page

1061 / 1069

Location

United States

Related Subject Headings

  • Triazoles
  • Transcriptome
  • Survival Rate
  • Receptors, Progesterone
  • Receptors, Estrogen
  • Proportional Hazards Models
  • Prognosis
  • Predictive Value of Tests
  • Oncology & Carcinogenesis
  • Nitriles
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Ellis, M. J., Suman, V. J., Hoog, J., Goncalves, R., Sanati, S., Creighton, C. J., … Hunt, K. (2017). 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, 35(10), 1061–1069. https://doi.org/10.1200/JCO.2016.69.4406
Ellis, Matthew J., Vera J. Suman, Jeremy Hoog, Rodrigo Goncalves, Souzan Sanati, Chad J. Creighton, Katherine DeSchryver, 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 35, no. 10 (April 1, 2017): 1061–69. https://doi.org/10.1200/JCO.2016.69.4406.
Ellis MJ, Suman VJ, Hoog J, Goncalves R, Sanati S, Creighton CJ, DeSchryver K, Crouch E, Brink A, Watson M, Luo J, Tao Y, Barnes M, Dowsett M, Budd GT, Winer E, Silverman P, Esserman L, Carey L, Ma CX, Unzeitig G, Pluard T, Whitworth P, Babiera G, Guenther JM, Dayao Z, Ota D, Leitch M, Olson JA, Allred DC, Hunt K. 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 Apr 1;35(10):1061–1069.

Published In

J Clin Oncol

DOI

EISSN

1527-7755

Publication Date

April 1, 2017

Volume

35

Issue

10

Start / End Page

1061 / 1069

Location

United States

Related Subject Headings

  • Triazoles
  • Transcriptome
  • Survival Rate
  • Receptors, Progesterone
  • Receptors, Estrogen
  • Proportional Hazards Models
  • Prognosis
  • Predictive Value of Tests
  • Oncology & Carcinogenesis
  • Nitriles