TY - JOUR
T1 - Evaluation of Sensitivity to Endocrine Therapy Index (SET2,3) for Response to Neoadjuvant Endocrine Therapy and Longer-Term Breast Cancer Patient Outcomes (Alliance Z1031)
AU - Suman, Vera J.
AU - Du, Lili
AU - Hoskin, Tanya
AU - Anurag, Meenakshi
AU - Ma, Cynthia
AU - Bedrosian, Isabelle
AU - Hunt, Kelly K.
AU - Ellis, Matthew J.
AU - Symmans, W. Fraser
N1 - Funding Information:
personal fees from Gilead, AstraZeneca, Sanofi-Genzyme, Jacobio, Natera, Novartis, Inivata, Athenex, Bayer, Eisai, and Seattle Genetics; and grants from Puma and Pfizer outside the submitted work. K.K. Hunt reports other support from American College of Surgeons Oncology Group outside the submitted work; and is medical advisory board member of Armada Health and AstraZeneca and reports research funding to institution from Cairn Surgical, Eli Lilly & Co., and Lumicell. M.J. Ellis reports other support from Bioclassifier during the conduct of the study and other support from AstraZeneca outside the submitted work; in addition, M.J. Ellis has a patent for PAM50 issued, licensed, and with royalties paid from Veracyte. W.F. Symmans reports grants from Breast Cancer Research Foundation (BCRF-158) and Cancer Prevention and Research Institute of Texas (RP180712) during the conduct of the study and other support from Delphi Diagnostics, Inc, IONIS Pharmaceuticals, Eiger Biopharmaceuticals, personal fees from Merck and AstraZeneca, and grants from Pfizer outside the submitted work; in addition, W.F. Symmans has a patent for “Targeted Measure of Transcriptional Activity Related to Hormone Receptors,” United States, Provisional Patent Application Serial No. 62/329,774 pending to Delphi Diagnostics Inc. No disclosures were reported by the other authors.
Funding Information:
Research reported in this publication was supported by the NIH under award numbers U10CA180821, U10CA180882, and U24CA196171 (to the Alliance for Clinical Trials in Oncology); UG1CA233329, UG1CA233339; Cancer Prevention and Research Institute of Texas (CPRIT, RP180712, to W.F. Symmans, K.K. Hunt); Breast Cancer Research Foundation (BCRF-158, to W.F. Symmans). Also, NIH/NCI R01 CA095614 (M.J. Ellis) and the Baylor SPORE in Breast Cancer 2P50CA186784 (M.J. Ellis and V.J. Suman). M.J. Ellis is a Susan G. Komen Foundation Scholar emeritus, a McNair Scholar supported by the McNair Medical Institute at The Robert and Janice McNair Foundation, and a recipient of a CPRIT (Cancer Prevention and Research Institute of Texas) Established Investigator Award (RR140027). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.
Publisher Copyright:
© 2022 The Authors.
PY - 2022/8/1
Y1 - 2022/8/1
N2 - Purpose: To evaluate prediction of response and event-free survival (EFS) following neoadjuvant endocrine therapy by SET2,3 index of nonproliferation gene expression related to estrogen and progesterone receptors adjusted for baseline prognosis. Experimental Design: A correlative study was conducted of SET2,3 measured from gene expression profiles of diagnostic tumor (Agilent microarrays) in 379 women with cStage II-III breast cancer from the American College of Surgeons Oncology Group Z1031 neoadjuvant aromatase inhibitor trial SET2,3 was dichotomized using the previously published cutoff. Fisher exact test was used to assess the association between SET2,3 and low proliferation at week 2-4 [Ki67 ≤ 10% or complete cell-cycle arrest (CCCA; Ki67 ≤ 2.7%)] and PEPI-0 rate in cohort B, and the association between SET2,3 and ypStage 0/I in all patients. Cox models were used to assess EFS with respect to SET2,3 excluding cohort B patients who switched to chemotherapy. Results: Patients with high SET2,3 had higher rate of pharmacodynamic response than patients with low SET2,3 (Ki67 ≤ 10% in 88.2% vs. 56.9%, P < 0.0001; CCCA in 50.0% vs. 26.2%, P=0.0054), but rate of ypStage 0/I (24.0% vs. 20.4%, P = 0.4580) or PEPI = 0 (28.4% vs. 20.6%, P = 0.3419) was not different. Patients with high SET2,3 had longer EFS than patients with low SET2,3 (HR, 0.52, 95% confidence interval: 0.34-0.80; P = 0.0026). Conclusions: This exploratory analysis of Z1031 data demonstrated a higher rate of pharmacodynamic suppression of proliferation and longer EFS in high SET2,3 disease relative to low SET2,3 disease. The ypStage 0/I rate and PEPI = 0 rate were similar with respect to SET2,3.
AB - Purpose: To evaluate prediction of response and event-free survival (EFS) following neoadjuvant endocrine therapy by SET2,3 index of nonproliferation gene expression related to estrogen and progesterone receptors adjusted for baseline prognosis. Experimental Design: A correlative study was conducted of SET2,3 measured from gene expression profiles of diagnostic tumor (Agilent microarrays) in 379 women with cStage II-III breast cancer from the American College of Surgeons Oncology Group Z1031 neoadjuvant aromatase inhibitor trial SET2,3 was dichotomized using the previously published cutoff. Fisher exact test was used to assess the association between SET2,3 and low proliferation at week 2-4 [Ki67 ≤ 10% or complete cell-cycle arrest (CCCA; Ki67 ≤ 2.7%)] and PEPI-0 rate in cohort B, and the association between SET2,3 and ypStage 0/I in all patients. Cox models were used to assess EFS with respect to SET2,3 excluding cohort B patients who switched to chemotherapy. Results: Patients with high SET2,3 had higher rate of pharmacodynamic response than patients with low SET2,3 (Ki67 ≤ 10% in 88.2% vs. 56.9%, P < 0.0001; CCCA in 50.0% vs. 26.2%, P=0.0054), but rate of ypStage 0/I (24.0% vs. 20.4%, P = 0.4580) or PEPI = 0 (28.4% vs. 20.6%, P = 0.3419) was not different. Patients with high SET2,3 had longer EFS than patients with low SET2,3 (HR, 0.52, 95% confidence interval: 0.34-0.80; P = 0.0026). Conclusions: This exploratory analysis of Z1031 data demonstrated a higher rate of pharmacodynamic suppression of proliferation and longer EFS in high SET2,3 disease relative to low SET2,3 disease. The ypStage 0/I rate and PEPI = 0 rate were similar with respect to SET2,3.
UR - http://www.scopus.com/inward/record.url?scp=85135596668&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-22-0068
DO - 10.1158/1078-0432.CCR-22-0068
M3 - Article
C2 - 35653124
AN - SCOPUS:85135596668
SN - 1078-0432
VL - 28
SP - 3287
EP - 3295
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 15
ER -