Comparison of prognostic and predictive impact of genomic or central grade and immunohistochemical subtypes or IHC4 in HR+/HER2-early breast cancer: WSG-AGO EC-Doc Trial

被引：13

作者：

Gluz, O. ^{[1
,2
]}

Liedtke, C. ^{[1
,3
]}

Huober, J. ^{[4
,5
]}

Peyro-Saint-Paul, H. ^{[6
]}

Kates, R. E. ^{[1
]}

Kreipe, H. H. ^{[7
]}

Hartmann, A. ^{[8
]}

Pelz, E. ^{[9
]}

Erber, R. ^{[8
]}

Mohrmann, S. ^{[10
]}

Moebus, V. ^{[11
]}

Augustin, D. ^{[12
]}

Hoffmann, G. ^{[13
]}

Thomssen, C. ^{[14
,15
]}

Jaenicke, F. ^{[14
]}

Kiechle, M. ^{[16
]}

Wallwiener, D. ^{[4
]}

Kuhn, W. ^{[17
]}

Nitz, U. ^{[1
,2
]}

Harbeck, N. ^{[1
,18
,19
]}

机构：

[1] West German Study Grp, Monchengladbach, Germany

[2] Ev Bethesda Hosp, Breast Ctr Niederrhein, D-41061 Monchengladbach, Germany

[3] Univ Clin Schleswig Holstein, Womens Clin, Lubeck, Germany

[4] Univ Tubingen, Dept Obstet & Gynecol, Tubingen, Germany

[5] Univ Ulm, Dept Obstet & Gynecol, D-89069 Ulm, Germany

[6] QIAGEN, Sample & Assay Technol, Marseille, France

[7] Hannover Med Sch, Inst Pathol, Hannover, Germany

[8] Univ Clin Erlangen, Inst Pathol, Erlangen, Germany

[9] Inst Pathol Viersen, Viersen, Germany

[10] Univ Dusseldorf, Dept Obstet & Gynecol, Dusseldorf, Germany

[11] Staedt Klinikum, Dept Obstet & Gynecol, Frankfurt, Germany

[12] Clin Deggendorf Mammactr Ostbayern, Deggendorf, Germany

[13] St Josephs Hosp, Dept Gynecol & Obstet, Wiesbaden, Germany

[14] Univ Med Ctr Hamburg Eppendorf, Dept Gynecol, Hamburg, Germany

[15] Univ Hosp Halle Saale, Dept Gynecol, Halle, Germany

[16] Tech Univ Munich, Klinikum Rechts Isar, Dept Gynecol & Obstet, D-80290 Munich, Germany

[17] Univ Hosp Bonn, Dept Gynecol & Obstet, Bonn, Germany

[18] Univ Munich, Breast Ctr, Munich, Germany

[19] CCC LMU, Munich, Germany

来源：

ANNALS OF ONCOLOGY | 2016年 / 27卷 / 06期

关键词：

breast cancer subtypes; prognosis; genomic grade index; central grade; INTERNATIONAL EXPERT CONSENSUS; PROGESTERONE-RECEPTOR; ESTROGEN-RECEPTOR; RECURRENCE SCORE; KI67; EXPRESSION; DISTANT RECURRENCE; ENDOCRINE THERAPY; PAM50; RISK; PACLITAXEL; DOCETAXEL;

D O I：

10.1093/annonc/mdw070

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Introduction: Potential prognostic and predictive markers in early, intermediate-risk breast cancer (BC) include histological grade, Ki-67, genomic signatures, e.g. genomic grade index (GGI), and intrinsic subtypes. Their prognostic/predictive impact in hormone receptor (HR: ER and/or PR) positive/HER2- BC is controversial. WSG-AGO EC-Doc demonstrated superior event-free survival (EFS) in patients with 1-3 positive lymph node receiving epirubicin/cyclophosphamide-docetaxel (EC-Doc) versus 5-fluoruracil/epirubicin/cyclophosphamide (FEC). In a representative trial subset, we quantify concordance among factors used for clinical chemotherapy indication. We investigate the impact of central histology (n = 772), immunohistochemistry for intrinsic subtyping and IHC4, and dichotomous (GG) or continuous (GGI) genomic grade (n = 472) on patient outcome and benefit from taxane chemotherapy, focusing on HR+/HER2- patients (n = 459). Concordance of local grade (LG) with central (CG) or genomic grade was modest. In HR+/HER2- patients, low (GG-1: 16%), equivocal (GG-EQ: 17%), and high (GG-3: 67%) GG were associated with respective 5-year EFS of 100%, 93%, and 85%. GGI was prognostic for EFS within all LG subgroups and within CG3, whereas IHC4 was prognostic only in CG3 tumors. In unselected and HR+/HER2- patients, CG3 and luminal-A-like subtype entered the multivariate EFS model, but not IHC4 or GG. In the whole population, continuous GGI entered the model [hazard ratio (H.R.) of 75th versus 25th = 2.79; P = 0.01], displacing luminal-A-like subtype; within HR+/HER2- (H.R. = 5.36; P < 0.001), GGI was the only remaining prognostic factor. In multivariate interaction analysis (including central and genomic grade), luminal-B-like subtype [HR+ and (Ki-67 a parts per thousand yen20% or HER2+)] was predictive for benefit of EC-Doc versus FEC in unselected but not in HR+/HER2- patients. In the WSG-AGO EC-Doc trial for intermediate-risk BC, CG, intrinsic subtype (by IHC), and GG provide prognostic information. Continuous GGI (but not IHC4) adds prognostic information even when IHC subtype and CG are available. Finally, the high interobserver variability for histological grade and the still missing validation of Ki-67 preclude indicating or omitting adjuvant chemotherapy based on these single factors alone. The WSG-AGO/EC-Doc is registered at ClinicalTrials.gov, NCT02115204.

引用

页码：1035 / 1040

页数：6

共 26 条

[1] Comparison of the prognostic value of genomic grade index, Ki67 expression and mitotic activity index in early node-positive breast cancer patients [J].

Bertucci, F. ;

Finetti, P. ;

Roche, H. ;

Le Doussal, J. M. ;

Marisa, L. ;

Martin, A. L. ;

Lacroix-Triki, M. ;

Blanc-Fournier, C. ;

Jacquemier, J. ;

Peyro-Saint-Paul, H. ;

Viens, P. ;

Sotiriou, C. ;

Birnbaum, D. ;

Penault-Llorca, F. .

ANNALS OF ONCOLOGY, 2013, 24 (03) :625-632

[2] The impact of inter-observer variation in pathological assessment of node-negative breast cancer on clinical risk assessment and patient selection for adjuvant systemic treatment [J].

Bueno-de-Mesquita, J. M. ;

Nuyten, D. S. A. ;

Wesseling, J. ;

van Tinteren, H. ;

Linn, S. C. ;

van de Vijver, M. J. .

ANNALS OF ONCOLOGY, 2010, 21 (01) :40-47

[3] Basal-like breast cancer defined by five biomarkers has superior prognostic value then triple-negative phenotype [J].

Cheang, Maggie C. U. ;

Voduc, David ;

Bajdik, Chris ;

Leung, Samuel ;

McKinney, Steven ;

Chia, Stephen K. ;

Perou, Charles M. ;

Nielsen, Torsten O. .

CLINICAL CANCER RESEARCH, 2008, 14 (05) :1368-1376

[4] Ki67 Index, HER2 Status, and Prognosis of Patients With Luminal B Breast Cancer [J].

Cheang, Maggie C. U. ;

Chia, Stephen K. ;

Voduc, David ;

Gao, Dongxia ;

Leung, Samuel ;

Snider, Jacqueline ;

Watson, Mark ;

Davies, Sherri ;

Bernard, Philip S. ;

Parker, Joel S. ;

Perou, Charles M. ;

Ellis, Matthew J. ;

Nielsen, Torsten O. .

JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, 2009, 101 (10) :736-750

[5] Tailoring therapies-improving the management of early breast cancer: St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2015 [J].

Coates, A. S. ;

Winer, E. P. ;

Goldhirsch, A. ;

Gelber, R. D. ;

Gnant, M. ;

Piccart-Gebhart, M. ;

Thuerlimann, B. ;

Senn, H. -J. .

ANNALS OF ONCOLOGY, 2015, 26 (08) :1533-1546

[6] Prognostic Value of a Combined Estrogen Receptor, Progesterone Receptor, Ki-67, and Human Epidermal Growth Factor Receptor 2 Immunohistochemical Score and Comparison With the Genomic Health Recurrence Score in Early Breast Cancer [J].

Cuzick, Jack ;

Dowsett, Mitch ;

Pineda, Silvia ;

Wale, Christopher ;

Salter, Janine ;

Quinn, Emma ;

Zabaglo, Lila ;

Mallon, Elizabeth ;

Green, Andrew R. ;

Ellis, Ian O. ;

Howell, Anthony ;

Buzdar, Aman U. ;

Forbes, John F. .

JOURNAL OF CLINICAL ONCOLOGY, 2011, 29 (32) :4273-4278

[7] Ki67 levels as predictive and prognostic parameters in pretherapeutic breast cancer core biopsies: a translational investigation in the neoadjuvant GeparTrio trial† [J].

Denkert, C. ;

Loibl, S. ;

Mueller, B. M. ;

Eidtmann, H. ;

Schmitt, W. D. ;

Eiermann, W. ;

Gerber, B. ;

Tesch, H. ;

Hilfrich, J. ;

Huober, J. ;

Fehm, T. ;

Barinoff, J. ;

Jackisch, C. ;

Prinzler, J. ;

Ruediger, T. ;

Erbstoesser, E. ;

Blohmer, J. U. ;

Budczies, J. ;

Mehta, K. M. ;

von Minckwitz, G. .

ANNALS OF ONCOLOGY, 2013, 24 (11) :2786-2793

[8] Comparison of PAM50 Risk of Recurrence Score With Oncotype DX and IHC4 for Predicting Risk of Distant Recurrence After Endocrine Therapy [J].

Dowsett, Mitch ;

Sestak, Ivana ;

Lopez-Knowles, Elena ;

Sidhu, Kalvinder ;

Dunbier, Anita K. ;

Cowens, J. Wayne ;

Ferree, Sean ;

Storhoff, James ;

Schaper, Carl ;

Cuzick, Jack .

JOURNAL OF CLINICAL ONCOLOGY, 2013, 31 (22) :2783-+

[9] Assessment of Ki67 in Breast Cancer: Recommendations from the International Ki67 in Breast Cancer Working Group [J].

Dowsett, Mitch ;

Nielsen, Torsten O. ;

A'Hern, Roger ;

Bartlett, John ;

Coombes, R. Charles ;

Cuzick, Jack ;

Ellis, Matthew ;

Henry, N. Lynn ;

Hugh, Judith C. ;

Lively, Tracy ;

McShane, Lisa ;

Paik, Soon ;

Penault-Llorca, Frederique ;

Prudkin, Ljudmila ;

Regan, Meredith ;

Salter, Janine ;

Sotiriou, Christos ;

Smith, Ian E. ;

Viale, Giuseppe ;

Zujewski, Jo Anne ;

Hayes, Daniel F. .

JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, 2011, 103 (22) :1656-1664

[10] Identifying clinically relevant prognostic subgroups of postmenopausal women with node-positive hormone receptor-positive early-stage breast cancer treated with endocrine therapy: a combined analysis of ABCSG-8 and ATAC using the PAM50 risk of recurrence score and intrinsic subtype [J].

Gnant, M. ;

Sestak, I. ;

Filipits, M. ;

Dowsett, M. ;

Balic, M. ;

Lopez-Knowles, E. ;

Greil, R. ;

Dubsky, P. ;

Stoeger, H. ;

Rudas, M. ;

Jakesz, R. ;

Ferree, S. ;

Cowens, J. W. ;

Nielsen, T. ;

Schaper, C. ;

Fesl, C. ;

Cuzick, J. .

ANNALS OF ONCOLOGY, 2015, 26 (08) :1685-1691

← 1 2 3 →