Randomized phase II neoadjuvant comparison between letrozole, anastrozole, and exemestane for postmenopausal women with estrogen receptor-rich stage 2 to 3 breast cancer

Clinical and biomarker outcomes and predictive value of the baseline PAM50-based intrinsic subtype - ACOSOG Z1031

Matthew J. Ellis, Vera J. Suman, Jeremy Hoog, Li Lin, Jacqueline Snider, Aleix Prat, Joel S. Parker, Jingqin Luo, Katherine DeSchryver, D. Craig Allred, Laura J. Esserman, Gary W. Unzeitig, Julie Margenthaler, Gildy V. Babiera, P. Kelly Marcom, Joseph M. Guenther, Mark A. Watson, Marilyn Leitch, Kelly Hunt, John A. Olson

Research output: Contribution to journalArticle

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Abstract

Purpose: Preoperative aromatase inhibitor (AI) treatment promotes breast-conserving surgery (BCS) for estrogen receptor (ER) -positive breast cancer. To study this treatment option, responses to three AIs were compared in a randomized phase II neoadjuvant trial designed to select agents for phase III investigations. Patients and Methods: Three hundred seventy-seven postmenopausal women with clinical stage II to III ER-positive (Allred score 6-8) breast cancer were randomly assigned to receive neoadjuvant exemestane, letrozole, or anastrozole. The primary end point was clinical response. Secondary end points included BCS, Ki67 proliferation marker changes, the Preoperative Endocrine Prognostic Index (PEPI), and PAM50-based intrinsic subtype analysis. Results: On the basis of clinical response rates, letrozole and anastrozole were selected for further investigation; however, no other differences in surgical outcome, PEPI score, or Ki67 suppression were detected. The BCS rate for mastectomy-only patients at presentation was 51%. PAM50 analysis identified AI-unresponsive nonluminal subtypes (human epidermal growth factor receptor 2 enriched or basal-like) in 3.3% of patients. Clinical response and surgical outcomes were similar in luminal A (LumA) versus luminal B tumors; however, a PEPI of 0 (best prognostic group) was highest in the LumA subset (27.1% v 10.7%; P = .004). Conclusion: Neoadjuvant AI treatment markedly improved surgical outcomes. Ki67 and PEPI data demonstrated that the three agents tested are biologically equivalent and therefore likely to have similar adjuvant activities. LumA tumors were more likely to have favorable biomarker characteristics after treatment; however, occasional paradoxical increases in Ki67 (12% of tumors with > 5% increase after therapy) suggest treatment-resistant cells, present in some LumA tumors, can be detected by post-treatment profiling.

Original languageEnglish (US)
Pages (from-to)2342-2349
Number of pages8
JournalJournal of Clinical Oncology
Volume29
Issue number17
DOIs
StatePublished - Jun 10 2011

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exemestane
letrozole
Tumor Biomarkers
Estrogen Receptors
Breast
Aromatase Inhibitors
Segmental Mastectomy
Therapeutics
Neoplasms
Breast Neoplasms
Mastectomy
anastrozole

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Randomized phase II neoadjuvant comparison between letrozole, anastrozole, and exemestane for postmenopausal women with estrogen receptor-rich stage 2 to 3 breast cancer : Clinical and biomarker outcomes and predictive value of the baseline PAM50-based intrinsic subtype - ACOSOG Z1031. / Ellis, Matthew J.; Suman, Vera J.; Hoog, Jeremy; Lin, Li; Snider, Jacqueline; Prat, Aleix; Parker, Joel S.; Luo, Jingqin; DeSchryver, Katherine; Allred, D. Craig; Esserman, Laura J.; Unzeitig, Gary W.; Margenthaler, Julie; Babiera, Gildy V.; Marcom, P. Kelly; Guenther, Joseph M.; Watson, Mark A.; Leitch, Marilyn; Hunt, Kelly; Olson, John A.

In: Journal of Clinical Oncology, Vol. 29, No. 17, 10.06.2011, p. 2342-2349.

Research output: Contribution to journalArticle

Ellis, MJ, Suman, VJ, Hoog, J, Lin, L, Snider, J, Prat, A, Parker, JS, Luo, J, DeSchryver, K, Allred, DC, Esserman, LJ, Unzeitig, GW, Margenthaler, J, Babiera, GV, Marcom, PK, Guenther, JM, Watson, MA, Leitch, M, Hunt, K & Olson, JA 2011, 'Randomized phase II neoadjuvant comparison between letrozole, anastrozole, and exemestane for postmenopausal women with estrogen receptor-rich stage 2 to 3 breast cancer: Clinical and biomarker outcomes and predictive value of the baseline PAM50-based intrinsic subtype - ACOSOG Z1031', Journal of Clinical Oncology, vol. 29, no. 17, pp. 2342-2349. https://doi.org/10.1200/JCO.2010.31.6950
Ellis, Matthew J. ; Suman, Vera J. ; Hoog, Jeremy ; Lin, Li ; Snider, Jacqueline ; Prat, Aleix ; Parker, Joel S. ; Luo, Jingqin ; DeSchryver, Katherine ; Allred, D. Craig ; Esserman, Laura J. ; Unzeitig, Gary W. ; Margenthaler, Julie ; Babiera, Gildy V. ; Marcom, P. Kelly ; Guenther, Joseph M. ; Watson, Mark A. ; Leitch, Marilyn ; Hunt, Kelly ; Olson, John A. / Randomized phase II neoadjuvant comparison between letrozole, anastrozole, and exemestane for postmenopausal women with estrogen receptor-rich stage 2 to 3 breast cancer : Clinical and biomarker outcomes and predictive value of the baseline PAM50-based intrinsic subtype - ACOSOG Z1031. In: Journal of Clinical Oncology. 2011 ; Vol. 29, No. 17. pp. 2342-2349.
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abstract = "Purpose: Preoperative aromatase inhibitor (AI) treatment promotes breast-conserving surgery (BCS) for estrogen receptor (ER) -positive breast cancer. To study this treatment option, responses to three AIs were compared in a randomized phase II neoadjuvant trial designed to select agents for phase III investigations. Patients and Methods: Three hundred seventy-seven postmenopausal women with clinical stage II to III ER-positive (Allred score 6-8) breast cancer were randomly assigned to receive neoadjuvant exemestane, letrozole, or anastrozole. The primary end point was clinical response. Secondary end points included BCS, Ki67 proliferation marker changes, the Preoperative Endocrine Prognostic Index (PEPI), and PAM50-based intrinsic subtype analysis. Results: On the basis of clinical response rates, letrozole and anastrozole were selected for further investigation; however, no other differences in surgical outcome, PEPI score, or Ki67 suppression were detected. The BCS rate for mastectomy-only patients at presentation was 51{\%}. PAM50 analysis identified AI-unresponsive nonluminal subtypes (human epidermal growth factor receptor 2 enriched or basal-like) in 3.3{\%} of patients. Clinical response and surgical outcomes were similar in luminal A (LumA) versus luminal B tumors; however, a PEPI of 0 (best prognostic group) was highest in the LumA subset (27.1{\%} v 10.7{\%}; P = .004). Conclusion: Neoadjuvant AI treatment markedly improved surgical outcomes. Ki67 and PEPI data demonstrated that the three agents tested are biologically equivalent and therefore likely to have similar adjuvant activities. LumA tumors were more likely to have favorable biomarker characteristics after treatment; however, occasional paradoxical increases in Ki67 (12{\%} of tumors with > 5{\%} increase after therapy) suggest treatment-resistant cells, present in some LumA tumors, can be detected by post-treatment profiling.",
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T1 - Randomized phase II neoadjuvant comparison between letrozole, anastrozole, and exemestane for postmenopausal women with estrogen receptor-rich stage 2 to 3 breast cancer

T2 - Clinical and biomarker outcomes and predictive value of the baseline PAM50-based intrinsic subtype - ACOSOG Z1031

AU - Ellis, Matthew J.

AU - Suman, Vera J.

AU - Hoog, Jeremy

AU - Lin, Li

AU - Snider, Jacqueline

AU - Prat, Aleix

AU - Parker, Joel S.

AU - Luo, Jingqin

AU - DeSchryver, Katherine

AU - Allred, D. Craig

AU - Esserman, Laura J.

AU - Unzeitig, Gary W.

AU - Margenthaler, Julie

AU - Babiera, Gildy V.

AU - Marcom, P. Kelly

AU - Guenther, Joseph M.

AU - Watson, Mark A.

AU - Leitch, Marilyn

AU - Hunt, Kelly

AU - Olson, John A.

PY - 2011/6/10

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N2 - Purpose: Preoperative aromatase inhibitor (AI) treatment promotes breast-conserving surgery (BCS) for estrogen receptor (ER) -positive breast cancer. To study this treatment option, responses to three AIs were compared in a randomized phase II neoadjuvant trial designed to select agents for phase III investigations. Patients and Methods: Three hundred seventy-seven postmenopausal women with clinical stage II to III ER-positive (Allred score 6-8) breast cancer were randomly assigned to receive neoadjuvant exemestane, letrozole, or anastrozole. The primary end point was clinical response. Secondary end points included BCS, Ki67 proliferation marker changes, the Preoperative Endocrine Prognostic Index (PEPI), and PAM50-based intrinsic subtype analysis. Results: On the basis of clinical response rates, letrozole and anastrozole were selected for further investigation; however, no other differences in surgical outcome, PEPI score, or Ki67 suppression were detected. The BCS rate for mastectomy-only patients at presentation was 51%. PAM50 analysis identified AI-unresponsive nonluminal subtypes (human epidermal growth factor receptor 2 enriched or basal-like) in 3.3% of patients. Clinical response and surgical outcomes were similar in luminal A (LumA) versus luminal B tumors; however, a PEPI of 0 (best prognostic group) was highest in the LumA subset (27.1% v 10.7%; P = .004). Conclusion: Neoadjuvant AI treatment markedly improved surgical outcomes. Ki67 and PEPI data demonstrated that the three agents tested are biologically equivalent and therefore likely to have similar adjuvant activities. LumA tumors were more likely to have favorable biomarker characteristics after treatment; however, occasional paradoxical increases in Ki67 (12% of tumors with > 5% increase after therapy) suggest treatment-resistant cells, present in some LumA tumors, can be detected by post-treatment profiling.

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