1. 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)
- Author
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Kelly K. Hunt, Erika C. Crouch, Yu Tao, Rodrigo Franco Gonçalves, Lisa A. Carey, Timothy J. Pluard, Gary Unzeitig, Mitchell Dowsett, Marilyn Leitch, Pat Whitworth, Eric P. Winer, Chad J. Creighton, G. Thomas Budd, John A. Olson, David M. Ota, D. Craig Allred, Vera J. Suman, Katherine DeSchryver, Jingqin Luo, Jeremy Hoog, Cynthia X. Ma, Laura J. Esserman, Amy Brink, Mark A. Watson, Matthew J. Ellis, Michael Barnes, Paula Silverman, Zoneddy Dayao, Gildy Babiera, Souzan Sanati, and J. Michael Guenther
- Subjects
0301 basic medicine ,Oncology ,Cancer Research ,Proliferation index ,medicine.medical_treatment ,chemistry.chemical_compound ,0302 clinical medicine ,Exemestane ,Receptors ,Antineoplastic Combined Chemotherapy Protocols ,Neoplasm Metastasis ,Neoadjuvant therapy ,Progesterone ,Aromatase Inhibitors ,Letrozole ,ORIGINAL REPORTS ,Middle Aged ,Prognosis ,Neoadjuvant Therapy ,3. Good health ,Survival Rate ,Local ,030220 oncology & carcinogenesis ,Female ,medicine.drug ,medicine.medical_specialty ,medicine.drug_class ,Clinical Decision-Making ,Clinical Sciences ,Oncology and Carcinogenesis ,Anastrozole ,Breast Neoplasms ,03 medical and health sciences ,Breast cancer ,Predictive Value of Tests ,Internal medicine ,Breast Cancer ,Nitriles ,medicine ,Mitotic Index ,Humans ,Oncology & Carcinogenesis ,Survival rate ,Neoplasm Staging ,Proportional Hazards Models ,Aged ,Aromatase inhibitor ,business.industry ,Triazoles ,medicine.disease ,Estrogen ,Androstadienes ,030104 developmental biology ,Neoplasm Recurrence ,Ki-67 Antigen ,chemistry ,business ,Transcriptome ,Follow-Up Studies - 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 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).
- Published
- 2017