Prognostic and predictive investigation of PAM50 intrinsic subtypes in the NCIC CTG MA.21 phase III chemotherapy trial

被引：37

作者：

Liu, Shuzhen ^{[1
,2
]}

Chapman, Judy-Anne W. ^{[3
]}

Burnell, Margot J. ^{[4
]}

Levine, Mark N. ^{[5
]}

Pritchard, Kathleen I. ^{[6
,7
]}

Whelan, Timothy J. ^{[8
]}

Rugo, Hope S. ^{[9
]}

Albain, Kathy S. ^{[10
]}

Perez, Edith A. ^{[11
]}

Virk, Shakeel ^{[3
]}

Barry, Garrett ^{[1
,2
]}

Gao, Dongxia ^{[1
,2
]}

O'Brien, Patti ^{[3
]}

Shepherd, Lois E. ^{[3
]}

Nielsen, Torsten O. ^{[1
,2
]}

Gelmon, Karen A. ^{[12
]}

机构：

[1] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada

[2] Vancouver Coastal Hlth Res Inst, Vancouver, BC V6H 3Z6, Canada

[3] Queens Univ, NCIC Clin Trials Grp, Kingston, ON, Canada

[4] St Johns Hosp, St John, NB, Canada

[5] McMaster Univ, Ontario Clin Oncol Grp, Hamilton, ON, Canada

[6] Sunnybrook Odette Canc Ctr, Toronto, ON, Canada

[7] Univ Toronto, Toronto, ON, Canada

[8] Juravinski Canc Ctr, Hamilton, ON, Canada

[9] Univ Calif San Francisco, Ctr Comprehens Canc, San Francisco, CA 94143 USA

[10] Loyola Univ, Med Ctr, Maywood, IL 60153 USA

[11] Mayo Clin, Jacksonville, FL 32224 USA

[12] British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada

来源：

BREAST CANCER RESEARCH AND TREATMENT | 2015年 / 149卷 / 02期

关键词：

PAM50; classification; Breast cancer; Clinical trial; Predictive effect; Survival analysis; POSITIVE BREAST-CANCER; DOXORUBICIN PLUS CYCLOPHOSPHAMIDE; ADJUVANT CHEMOTHERAPY; DISTANT RECURRENCE; NEOADJUVANT CHEMOTHERAPY; DOCETAXEL; PACLITAXEL; RISK; EXPRESSION; SCORE;

D O I：

10.1007/s10549-014-3259-1

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

PAM50-defined breast cancer intrinsic subtypes and risk-of-relapse (ROR) scores are prognostic and predictive of endocrine therapy and some chemotherapy. We investigated the prognostic and predictive effect of PAM50 classifications by chemotherapy type. NCIC CTG MA.21 randomized 2,104 patients to doxorubicin, cyclophosphamide, and paclitaxel (AC/T); dose-intense cyclophosphamide, epirubicin, and flurouracil (CEF); or dose-dense, dose-intense epirubicin, cyclophosphamide, and paclitaxel (EC/T). Patients were a parts per thousand currency sign60 years, with node-positive or high-risk node-negative disease, with median 8-year follow-up. Intrinsic subtypes and ROR were determined from RNA extracted from formalin-fixed paraffin-embedded sections by the NanoString PAM50 test. Univariate effects on relapse-free survival (RFS) were assessed with stratified log-rank test; multivariate analyses utilized stratified Cox regression. Among 1094 cases completing PAM50 intrinsic subtyping, 27 % were classified as luminal A, 23 % luminal B, 18 % HER2E, and 32 % basal-like. CEF and EC/T were superior to AC/T (p = 0.01). Higher continuous ROR was multivariately associated with worse RFS (p = 0.03), although categorical ROR was neither prognostic nor predictive. Intrinsic subtypes had a significant multivariate prognostic effect on RFS (p = 0.002). Compared with luminal A, hazard ratios were luminal B = 1.48 (95 % CI 0.92-2.37); HER2E = 2.68 (95 % CI 1.60-4.48); and basal-like = 1.97 (95 % CI 1.10-3.53). Intrinsic subtypes were not predictive of treatment benefit (AC/T vs. EC/T + CEF); however, subgroup analysis indicated subtypes (non-luminal vs. luminal) was predictive of taxane benefit (EC/T vs. CEF; p = 0.05). Both NanoString PAM50 subtypes and continuous ROR had significant prognostic effects on RFS for breast cancer patients treated with CEF, EC/T, and AC/T. Non-luminal tumors differentially responded to EC/T (with taxane) over CEF.

引用

页码：439 / 448

页数：10

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