Identification of biology-based breast cancer types with distinct predictive and prognostic features: role of steroid hormone and HER2 receptor expression in patients treated with neoadjuvant anthracycline/taxane-based chemotherapy

被引：91

作者：

Darb-Esfahani, Silvia ^{[1
]}

Loibl, Sibylle ^{[2
]}

Mueller, Berit M. ^{[1
]}

Roller, Marc ^{[2
]}

Denkert, Carsten ^{[1
]}

Komor, Martina ^{[2
]}

Schluens, Karsten ^{[1
]}

Blohmer, Jens Uwe ^{[3
]}

Budczies, Jan ^{[1
]}

Gerber, Bernd ^{[4
]}

Noske, Aurelia ^{[1
]}

du Bois, Andreas ^{[5
]}

Weichert, Wilko ^{[1
]}

Jackisch, Christian ^{[6
]}

Dietel, Manfred ^{[1
]}

Richter, Klaus ^{[7
]}

Kaufmann, Manfred ^{[8
]}

von Minckwitz, Gunter ^{[2
]}

机构：

[1] Charite, Inst Pathol, D-10117 Berlin, Germany

[2] GBG Forsch GmbH, D-63263 Neu Isenburg, Germany

[3] St Gertrauden Hosp, Dept Obstet & Gynecol, D-10713 Berlin, Germany

[4] Klinikum Sudstadt, Dept Obstet & Gynecol, D-18059 Rostock, Germany

[5] Dr Horst Schmidt Hosp HSK, Dept Gynecol & Gynecol Oncol, D-65199 Wiesbaden, Germany

[6] Klinikum Offenbach, Dept Obstet & Gynecol, D-63069 Offenbach, Germany

[7] Inst Pathol, D-30175 Hannover, Germany

[8] Univ Frankfurt Klinikum, Dept Obstet & Gynecol, D-60590 Frankfurt, Germany

来源：

BREAST CANCER RESEARCH | 2009年 / 11卷 / 05期

关键词：

PATHOLOGICAL COMPLETE RESPONSE; AND/OR PROGESTERONE-RECEPTORS; SURGICAL ADJUVANT BREAST; BOX BINDING PROTEIN-1; PREOPERATIVE CHEMOTHERAPY; SYSTEMIC TREATMENT; TUMOR RESPONSE; COEXPRESSION; DOXORUBICIN; THERAPY;

D O I：

10.1186/bcr2363

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Introduction Reliable predictive and prognostic markers for routine diagnostic purposes are needed for breast cancer patients treated with neoadjuvant chemotherapy. We evaluated protein biomarkers in a cohort of 116 participants of the GeparDuo study on anthracycline/taxane-based neoadjuvant chemotherapy for operable breast cancer to test for associations with pathological complete response (pCR) and disease-free survival (DFS). Particularly, we evaluated if interactions between hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) expression might lead to a different clinical behavior of HR+/HER2+ co-expressing and HR+/HER2-tumors and whether subgroups of triple negative tumors might be identified by the help of Ki67 labeling index, cytokeratin 5/6 (CK5/6), as well as cyclooxygenase-2 (COX-2), and Y-box binding protein 1 (YB-1) expression. Methods Expression analysis was performed using immunohistochemistry and silver-enhanced in situ hybridization on tissue microarrays (TMAs) of pretherapeutic core biopsies. Results pCR rates were significantly different between the biology-based tumor types (P = 0.044) with HR+/HER2+ and HR-/HER2-tumors having higher pCR rates than HR+/HER2-tumors. Ki67 labeling index, confirmed as significant predictor of pCR in the whole cohort (P = 0.001), identified HR-/HER-(triple negative) carcinomas with a higher chance for a pCR (P = 0.006). Biology-based tumor type (P = 0.046 for HR+/HER2+ vs. HR+/HER2-), Ki67 labeling index (P = 0.028), and treatment arm (P = 0.036) were independent predictors of pCR in a multivariate model. DFS was different in the biology-based tumor types (P < 0.0001) with HR+/HER2- and HR+/HER2+ tumors having the best prognosis and HR-/HER2+ tumors showing the worst outcome. Biology-based tumor type was an independent prognostic factor for DFS in multivariate analysis (P < 0.001). Conclusions Our data demonstrate that a biology-based breast cancer classification using estrogen receptor (ER), progesterone receptor (PgR), and HER2 bears independent predictive and prognostic potential. The HR+/HER2+ coexpressing carcinomas emerged as a group of tumors with a good response rate to neoadjuvant chemotherapy and a favorable prognosis. HR+/HER2-tumors had a good prognosis irrespective of a pCR, whereas patients with HR-/HER- and HR-/HER+ tumors, especially if they had not achieved a pCR, had an unfavorable prognosis and are in need of additional treatment options.

引用

页数：11

共 43 条

[1] High-throughput protein expression analysis using tissue microarray technology of a large well-characterised series identifies biologically distinct classes of breast cancer confirming recent cDNA expression analyses [J].