TY - JOUR

T1 - Prognostic value of Bcl-2 in two independent populations of estrogen receptor positive breast cancer patients treated with adjuvant endocrine therapy

AU - Larsen, Mathilde S

AU - Bjerre, Karsten

AU - Giobbie-Hurder, Anita

AU - Lænkholm, Anne-Vibeke

AU - Henriksen, Katrine L

AU - Ejlertsen, Bent

AU - Lykkesfeldt, Anne E

AU - Rasmussen, Birgitte B

PY - 2012/7

Y1 - 2012/7

N2 - INTRODUCTION: Estrogen receptor (ER) status is not an optimal marker for response to adjuvant endocrine therapy since approximately 30% of patients with ER-positive tumors eventually relapse. Bcl-2 is regulated by ER and may thus be considered as an indicator of ER activity and a candidate supplementary marker to ER status.PATIENTS AND METHODS: Tumor tissue from 257 patients with ER-positive breast cancer treated with tamoxifen was used for determination of the best threshold for immunohistochemical Bcl-2 assessment as prognostic marker. Subsequently, samples from the Danish patients of the randomized clinical trial BIG 1-98 comprising 1191 ER-positive patients treated with tamoxifen, letrozole or a sequence of the two were immunohistochemically stained for Bcl-2 to further explore the prognostic value of Bcl-2.RESULTS: Two Bcl-2 levels were found to divide the population of the primary study into significantly different groups according to disease-free survival (DFS). Multivariate analysis confirmed the significance of the lowest level, and showed Bcl-2 to be an independent prognostic marker. Analysis of the Danish cohort of the BIG 1-98 confirmed that Bcl-2 was a significant predictor of DFS, independent of known prognostic markers. However, in an additional analysis of a subset of the Danish cohort of BIG 1-98 including only HER-2 normal patients, the effect of Bcl-2 was not statistically significant.DISCUSSION: Low Bcl-2 can predict poor outcome of patients with ER-positive tumors treated with adjuvant endocrine therapy, whereas the use of Bcl-2 for determination of addition of chemotherapy was not supported by this study.

AB - INTRODUCTION: Estrogen receptor (ER) status is not an optimal marker for response to adjuvant endocrine therapy since approximately 30% of patients with ER-positive tumors eventually relapse. Bcl-2 is regulated by ER and may thus be considered as an indicator of ER activity and a candidate supplementary marker to ER status.PATIENTS AND METHODS: Tumor tissue from 257 patients with ER-positive breast cancer treated with tamoxifen was used for determination of the best threshold for immunohistochemical Bcl-2 assessment as prognostic marker. Subsequently, samples from the Danish patients of the randomized clinical trial BIG 1-98 comprising 1191 ER-positive patients treated with tamoxifen, letrozole or a sequence of the two were immunohistochemically stained for Bcl-2 to further explore the prognostic value of Bcl-2.RESULTS: Two Bcl-2 levels were found to divide the population of the primary study into significantly different groups according to disease-free survival (DFS). Multivariate analysis confirmed the significance of the lowest level, and showed Bcl-2 to be an independent prognostic marker. Analysis of the Danish cohort of the BIG 1-98 confirmed that Bcl-2 was a significant predictor of DFS, independent of known prognostic markers. However, in an additional analysis of a subset of the Danish cohort of BIG 1-98 including only HER-2 normal patients, the effect of Bcl-2 was not statistically significant.DISCUSSION: Low Bcl-2 can predict poor outcome of patients with ER-positive tumors treated with adjuvant endocrine therapy, whereas the use of Bcl-2 for determination of addition of chemotherapy was not supported by this study.

KW - Antineoplastic Agents, Hormonal/therapeutic use

KW - Breast Neoplasms/drug therapy

KW - Carcinoma, Ductal, Breast/drug therapy

KW - Chemotherapy, Adjuvant

KW - Double-Blind Method

KW - Female

KW - Humans

KW - Immunoenzyme Techniques

KW - In Situ Hybridization, Fluorescence

KW - Middle Aged

KW - Neoplasm Grading

KW - Prognosis

KW - Proto-Oncogene Proteins c-bcl-2/metabolism

KW - Receptor, ErbB-2/genetics

KW - Receptors, Estrogen/metabolism

KW - Retrospective Studies

KW - Survival Rate

KW - Tamoxifen/therapeutic use

KW - Tissue Array Analysis

U2 - 10.3109/0284186X.2011.653009

DO - 10.3109/0284186X.2011.653009

M3 - Journal article

C2 - 22462654

VL - 51

SP - 781

EP - 789

JO - Acta Oncologica

JF - Acta Oncologica

SN - 1100-1704

IS - 6

ER -