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)

Matthew J. Ellis, Vera J. Suman, Jeremy Hoog, Rodrigo Goncalves, Souzan Sanati, Chad J. Creighton, Katherine DeSchryver, Erika Crouch, Amy Brink, Mark Watson, Jingqin Luo, Yu Tao, Michael Barnes, Mitchell Dowsett, G. Thomas Budd, Eric Winer, Paula Silverman, Laura Esserman, Lisa Carey, Cynthia X. MaGary Unzeitig, Timothy Pluard, Pat Whitworth, Gildy Babiera, J. Michael Guenther, Zoneddy Dayao, David Ota, Marilyn Leitch, John A. Olson, D. Craig Allred, Kelly Hunt

Research output: Contribution to journalArticle

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Abstract

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 4weeks of neoadjuvant aromatase inhibitor (AI) therapy. A second objectivewas 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).

Original languageEnglish (US)
Pages (from-to)1061-1069
Number of pages9
JournalJournal of Clinical Oncology
Volume35
Issue number10
DOIs
StatePublished - Apr 1 2017

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Aromatase Inhibitors
Breast Neoplasms
Estrogen Receptors
Drug Therapy
Recurrence
exemestane
letrozole
Therapeutics
Neoadjuvant Therapy
Triage
Surgeons
Neoplasms
Clinical Trials
Genes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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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). / Ellis, Matthew J.; Suman, Vera J.; Hoog, Jeremy; Goncalves, Rodrigo; Sanati, Souzan; Creighton, Chad J.; DeSchryver, Katherine; Crouch, Erika; Brink, Amy; Watson, Mark; Luo, Jingqin; Tao, Yu; Barnes, Michael; Dowsett, Mitchell; Budd, G. Thomas; Winer, Eric; Silverman, Paula; Esserman, Laura; Carey, Lisa; Ma, Cynthia X.; Unzeitig, Gary; Pluard, Timothy; Whitworth, Pat; Babiera, Gildy; Guenther, J. Michael; Dayao, Zoneddy; Ota, David; Leitch, Marilyn; Olson, John A.; Allred, D. Craig; Hunt, Kelly.

In: Journal of Clinical Oncology, Vol. 35, No. 10, 01.04.2017, p. 1061-1069.

Research output: Contribution to journalArticle

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 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)', Journal of Clinical Oncology, vol. 35, no. 10, pp. 1061-1069. https://doi.org/10.1200/JCO.2016.69.4406
Ellis, Matthew J. ; Suman, Vera J. ; Hoog, Jeremy ; Goncalves, Rodrigo ; Sanati, Souzan ; Creighton, Chad J. ; DeSchryver, Katherine ; Crouch, Erika ; Brink, Amy ; Watson, Mark ; Luo, Jingqin ; Tao, Yu ; Barnes, Michael ; Dowsett, Mitchell ; Budd, G. Thomas ; Winer, Eric ; Silverman, Paula ; Esserman, Laura ; Carey, Lisa ; Ma, Cynthia X. ; Unzeitig, Gary ; Pluard, Timothy ; Whitworth, Pat ; Babiera, Gildy ; Guenther, J. Michael ; Dayao, Zoneddy ; Ota, David ; Leitch, Marilyn ; Olson, John A. ; Allred, D. Craig ; Hunt, Kelly. / 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). In: Journal of Clinical Oncology. 2017 ; Vol. 35, No. 10. pp. 1061-1069.
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title = "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)",
abstract = "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 4weeks of neoadjuvant aromatase inhibitor (AI) therapy. A second objectivewas 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).",
author = "Ellis, {Matthew J.} and Suman, {Vera J.} and Jeremy Hoog and Rodrigo Goncalves and Souzan Sanati and Creighton, {Chad J.} and Katherine DeSchryver and Erika Crouch and Amy Brink and Mark Watson and Jingqin Luo and Yu Tao and Michael Barnes and Mitchell Dowsett and Budd, {G. Thomas} and Eric Winer and Paula Silverman and Laura Esserman and Lisa Carey and Ma, {Cynthia X.} and Gary Unzeitig and Timothy Pluard and Pat Whitworth and Gildy Babiera and Guenther, {J. Michael} and Zoneddy Dayao and David Ota and Marilyn Leitch and Olson, {John A.} and Allred, {D. Craig} and Kelly Hunt",
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doi = "10.1200/JCO.2016.69.4406",
language = "English (US)",
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pages = "1061--1069",
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issn = "0732-183X",
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TY - JOUR

T1 - Ki67 proliferation index as a tool for chemotherapy decisions during and after neoadjuvant aromatase inhibitor treatment of breast cancer

T2 - Results from the American college of surgeons oncology group Z1031 trial (alliance)

AU - Ellis, Matthew J.

AU - Suman, Vera J.

AU - Hoog, Jeremy

AU - Goncalves, Rodrigo

AU - Sanati, Souzan

AU - Creighton, Chad J.

AU - DeSchryver, Katherine

AU - Crouch, Erika

AU - Brink, Amy

AU - Watson, Mark

AU - Luo, Jingqin

AU - Tao, Yu

AU - Barnes, Michael

AU - Dowsett, Mitchell

AU - Budd, G. Thomas

AU - Winer, Eric

AU - Silverman, Paula

AU - Esserman, Laura

AU - Carey, Lisa

AU - Ma, Cynthia X.

AU - Unzeitig, Gary

AU - Pluard, Timothy

AU - Whitworth, Pat

AU - Babiera, Gildy

AU - Guenther, J. Michael

AU - Dayao, Zoneddy

AU - Ota, David

AU - Leitch, Marilyn

AU - Olson, John A.

AU - Allred, D. Craig

AU - Hunt, Kelly

PY - 2017/4/1

Y1 - 2017/4/1

N2 - 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 4weeks of neoadjuvant aromatase inhibitor (AI) therapy. A second objectivewas 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).

AB - 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 4weeks of neoadjuvant aromatase inhibitor (AI) therapy. A second objectivewas 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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