Triple-negative phenotype is of adverse prognostic value in patients treated with dose-dense sequential adjuvant chemotherapy: a translational research analysis in the context of a Hellenic Cooperative Oncology Group (HeCOG) randomized phase III trial

被引：22

作者：

Skarlos, P. ^{[2
]}

Christodoulou, C. ^{[3
]}

Kalogeras, K. T. ^{[1
,4
]}

Eleftheraki, A. G. ^{[5
]}

Bobos, M. ^{[6
]}

Batistatou, A. ^{[7
]}

Valavanis, C. ^{[8
]}

Tzaida, O. ^{[8
]}

Timotheadou, E. ^{[1
]}

Kronenwett, R. ^{[9
]}

Wirtz, R. M. ^{[9
]}

Kostopoulos, I. ^{[10
]}

Televantou, D. ^{[6
]}

Koutselini, E. ^{[11
]}

Papaspirou, I. ^{[12
]}

Papadimitriou, C. A. ^{[13
]}

Pectasides, D. ^{[14
]}

Gogas, H. ^{[15
]}

Aravantinos, G. ^{[16
]}

Pavlidis, N. ^{[17
]}

Arapantoni, P. ^{[8
]}

Skarlos, D. V. ^{[3
]}

Fountzilas, G. ^{[1
]}

机构：

[1] Aristotle Univ Thessaloniki, Sch Med, Dept Med Oncol, Papageorgiou Hosp, GR-54006 Thessaloniki, Greece

[2] Agios Savvas Canc Hosp, Dept Radiotherapy, Athens, Greece

[3] Metropolitan Hosp, Dept Med Oncol 2, Piraeus, Greece

[4] Data Off, Translat Res Sect, Hellen Cooperat Oncol Grp, Athens, Greece

[5] Data Off, Biostat Sect, Hellen Cooperat Oncol Grp, Athens, Greece

[6] Aristotle Univ Thessaloniki, Sch Med, Mol Oncol Lab, Hellen Fdn Canc Res, GR-54006 Thessaloniki, Greece

[7] Ioannina Univ Hosp, Dept Pathol, Ioannina, Greece

[8] Metaxas Canc Hosp, Dept Pathol, Piraeus, Greece

[9] Siemens Healthcare Diagnost, Cologne, Germany

[10] Aristotle Univ Thessaloniki, Sch Med, Dept Pathol, GR-54006 Thessaloniki, Greece

[11] Metropolitan Hosp, Dept Pathol, Piraeus, Greece

[12] Alexandra Hosp, Dept Pathol, Athens, Greece

[13] Univ Athens, Sch Med, Dept Clin Therapeut, Alexandra Hosp, GR-11527 Athens, Greece

[14] Hippokrateion Hosp, Dept Internal Med 2, Oncol Sect, Athens, Greece

[15] Univ Athens, Sch Med, Dept Med 1, Laiko Gen Hosp, GR-11527 Athens, Greece

[16] Agii Anargiri Canc Hosp, Dept Med Oncol 3, Athens, Greece

[17] Ioannina Univ Hosp, Dept Med Oncol, Ioannina, Greece

来源：

CANCER CHEMOTHERAPY AND PHARMACOLOGY | 2012年 / 69卷 / 02期

关键词：

Immunophenotypic subtypes; mRNA subtypes; mRNA expression; Triple-negative breast cancer; HER2 enriched subtype; Prognostic value; PARAFFIN-EMBEDDED TISSUE; OPERABLE BREAST-CANCER; FLUOROURACIL CHEMOTHERAPY; COMBINATION CHEMOTHERAPY; RISK; CYCLOPHOSPHAMIDE; RECOMMENDATIONS; METHOTREXATE; MICROARRAYS; DOXORUBICIN;

D O I：

10.1007/s00280-011-1730-9

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

It is well recognized that breast cancer is a heterogeneous disease. The purpose of the current study was to classify patients according to the immunohistochemical phenotype of their tumors in an effort to evaluate the outcome of the respective groups of patients and specifically of those with triple-negative breast cancer (TNBC) following dose-dense sequential adjuvant chemotherapy. A total of 595 patients with high-risk breast cancer were treated with adjuvant anthracycline-based dose-dense sequential chemotherapy with or without paclitaxel in the context of a randomized study. ER, PgR, HER2, Ki67, EGFR, and CK5 protein expression were evaluated in 298 formalin-fixed paraffin-embedded tumor samples by immunohistochemistry (IHC). HER2 was also evaluated by chromogen in situ hybridization (CISH). HER2 status and Ki67 protein expression differentiated luminal IHC subtypes (luminal B tumors being HER2 and/or Ki67-positive). Among the 298 tumors, the immunohistochemical panel classified 37 (12%) as luminal A, 198 (66%) as luminal B, 27 (9%) as HER2 enriched, and 36 (12%) as TNBC. The median follow-up time was 97 months. Patients with luminal A tumors had the best prognosis, with improved disease-free survival (log-rank, P = 0.033) and overall survival (P = 0.006) compared with the other three tumor subtypes. The three subtypes had an increased risk for relapse and death compared with luminal A in multivariate analysis, as well. No benefit from paclitaxel treatment was detected in any of the four subtypes or the total cohort. Hierarchical clustering based on mRNA expression of ER, PgR, and HER2 by quantitative RT-PCR identified patient groups that were comparable to the subtypes identified by IHC. The results of this study confirm that triple negative, luminal B and HER2-enriched phenotypes identified by IHC are of adverse prognostic value in high-risk breast cancer patients treated with dose-dense sequential adjuvant chemotherapy.

引用

页码：533 / 546

页数：14

共 35 条

[31] Tissue microarrays: A powerful tool for high-throughput analysis of clinical specimens - A review of the method with validation data [J].

Skacel, M ;

Skilton, B ;

Pettay, JD ;

Tubbs, RR .

APPLIED IMMUNOHISTOCHEMISTRY & MOLECULAR MORPHOLOGY, 2002, 10 (01) :1-6

[32] Triple negative breast cancer:: molecular profiling and prognostic impact in adjuvant anthracycline-treated patients [J].

Tan, David S. P. ;

Marchio, Caterina ;

Jones, Robin L. ;

Savage, Kay ;

Smith, Ian E. ;

Dowsett, Mitch ;

Reis-Filho, Jorge S. .

BREAST CANCER RESEARCH AND TREATMENT, 2008, 111 (01) :27-44

[33] Chromogenic in situ hybridization -: A practical alternative for fluorescence in situ hybridization to detect HER-2/neu oncogene amplification in archival breast cancer samples [J].

Tanner, M ;

Gancberg, D ;

Di Leo, A ;

Larsimont, D ;

Rouas, G ;

Piccart, MJ ;

Isola, J .

AMERICAN JOURNAL OF PATHOLOGY, 2000, 157 (05) :1467-1472

[34]

Wolff AC, 2007, ARCH PATHOL LAB MED, V131, P18, DOI 10.1043/1543-2165(2007)131[18:ASOCCO]2.0.CO

[35]

← 1 2 3 4 →