Original Contribution| Volume 5, ISSUE 5, P364-369, December 2004

Potential Predictive Value of Bcl-2 for Response to Tamoxifen in the Adjuvant Setting of Node-Positive Breast Cancer

      This paper is only available as a PDF. To read, Please Download here.


      Approximately 50% of patients with estrogen receptor (ER)—positive breast cancer (BC) and 70%–80% of patients with ER-positive and progesterone receptor (PgR)—positive BC respond to hormonal therapy. Additional predictive markers are needed. A group of 287 patients with ER- and/or PgR-positive tumors was selected from 804 patients previously enrolled in a multicenter phase III trial. Bcl-2 expression was evaluated and correlated with response to adjuvant tamoxifen and survival. Estrogen receptor and PgR were determined by biochemical means and Bcl-2 by immunohistochemistry. With a median follow-up of 76 months (95 relapses and 60 deaths), of the 287 patients with, 187 (65%) had Bcl-2—positive tumors and 78 of these patients received tamoxifen. Of the 100 patients with Bcl-2—negative disease, 51 received tamoxifen and 49 regular follow-up. Using patients treated with tamoxifen as a reference, a univariate analysis of disease-free interval for patients who did not receive tamoxifen showed a hazard ratio (HR) of 1.42 (95% CI, 0.82-2.44;P = 0.21) for patients with Bcl-2—positive disease and a HR of 1.05 (95% CI, 0.55-1.99;P = 0.89) for patients with Bcl-2—negative disease (P = 0.48). After adjusting for number of positive lymph nodes, degree of receptor and PgR positivity, and type of surgery, the HRs were 1.54 (95% CI, 0.87–2.73;P = 0.14) for Bcl-2—positive disease and 1.05 (95% CI, 0.52–2.11; P = 0.88) for Bcl-2—negative disease. Despite its being a retrospective nonrandomized study with a relatively low number of patients, our results suggest that Bcl-2 deserves further evaluation as a predictive factor of sensitivity to tamoxifen.

      Key words

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Clinical Breast Cancer
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Goldhirsch A
        • Glick JH
        • Gelber RD
        • et al.
        Meeting highlights: international consensus panel on the treatment of primary cancer.
        J Clin Oncol. 2001; 19: 3817-3827
        • National Institutes of Health Consensus Development Panel
        National Institutes of Health Consensus Development Conference Statement: Adjuvant therapy for breast cancer, November 1-3, 2000.
        J Nat Cancer Inst. 2001; 93: 979-989
      1. Leek RD, Kaklamanis L, Pezzella F, et al. Bcl-2 in normal human breast and carcinoma, association with oestrogen receptor-positive, epidermal growth factor receptor-negative tumors and in situ cancer. Br J Cancer 199; 69:135-139.

        • Nathan B
        • Gusterson B
        • Jadayel D
        • et al.
        Expression of BCL-2 in primary breast cancer and its correlation with tumor phenotype. For the International (Ludwig) Breast Cancer Study Group.
        Ann Oncol. 1994; 5: 409-414
        • Hellemans P
        • van Dam PA
        • Weyler J
        • et al.
        Prognostic value of Bcl-2 expression in invasive breast cancer.
        Br J Cancer. 1995; 72: 354-360
        • Ceccarelli C
        • Santini D
        • Chieco P
        • et al.
        Multiple expression patterns of biopathological markers in primary invasive breast carcinoma: a useful tool for elucidating its biological behaviour.
        Ann Oncol. 1995; 6: 275-282
        • Silvestrini R
        • Veneroni S
        • Daidone MG
        • et al.
        The Bcl-2 protein: a prognostic indicator strongly related to p53 protein in lymph nodenegative breast cancer patients.
        J Natl Cancer Inst. 1994; 86: 499-504
        • Silvestrini R
        • Benini E
        • Veneroni S
        • et al.
        p53 and Bcl-2 expression correlates with clinical outcome in a series of node-positive breast cancer patients.
        J Clin Oncol. 1996; 14: 1604-1610
        • Castiglione F
        • Sarotto I
        • Fontana V
        • et al.
        Bcl-2, p53 and clinical outcome in a series of 138 operable breast cancer patients.
        Anticancer Res. 1999; 19: 4555-4563
        • Menard S
        • Casalini P
        • Tomasic G
        • et al.
        Pathobiologic identification of two distinct breast carcinoma subsets with diverging clinical behaviors.
        Breast Cancer Res Treat. 1999; 55: 169-177
        • Mauri FA
        • Maisonneuve P
        • Caffo O
        • et al.
        Prognostic value of estrogen receptor status can be improved by combined evaluation of p53, Bcl-2 and PgR expression: an immunohistochemical study on breast carcinoma with long-term follow-up.
        Int J Oncol. 1999; 15: 1137-1147
        • Joensuu H
        • Pylkkanen L
        • Toikkanen S
        Bcl-2 protein expression and long-term survival in breast cancer.
        Am J Pathol. 1994; 145: 1191-1198
        • Knowlton K
        • Mancini M
        • Creason S
        • et al.
        Bcl-2 slows in vitro breast cancer growth despite its antiapoptotic effect.
        J Surg Res. 1998; 76: 22-26
        • Gasparini G
        • Barbareschi M
        • Doglioni C
        • et al.
        Expression of Bcl-2 protein predicts efficacy of adjuvant treatments in operable node-positive breast cancer.
        Clin Cancer Res. 1995; 1: 189-198
        • Elledge RM
        • Green S
        • Howes L
        • et al.
        Bcl-2, p53, and response to tamoxifen in estrogen receptor-positive metastatic breast cancer: A Southwest Oncology Group Study.
        J Clin Oncol. 1997; 15: 1916-1922
        • Piccart MJ
        • Di Leo A
        • Beauduin M
        • et al.
        Phase III trial comparing two dose levels of epirubicin combined with cyclophosphamide with cyclophosphamide, methotrexate, and fluorouracil in node-positive breast cancer.
        J Clin Oncol. 2001; 19: 3103-3110
        • Peto R
        Fifth meeting of the Early Breast Cancer Trialists' Collaborative Group, Oxford, UKSeptember 2000
        • Early Breast Cancer Trialists' Collaborative Group
        Tamoxifen for early breast cancer: an overview of the randomized trials.
        Lancet. 1998; 351: 1451-1467
        • Di Leo A
        • Cardoso F
        • Scohy S
        • et al.
        Predictive molecular markers: a new window of opportunity in the adjuvant therapy of breast cancer.
        in: Naboltz JM Tonkin K Aapro MS Breast Cancer Management-Application of Clinical and Translational Evidence to Patient Care. 2nd ed. Lippincott Williams & Wilkins, Philadelphia2002: 367-382
        • Perou C
        • Sørlie T
        • Eisen M
        • et al.
        Molecular portraits of human breast tumors.
        Nature. 2000; 406: 747-752
        • Sørlie T
        • Perou CM
        • Tibshirani R
        • et al.
        Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications.
        Proc Natl Acad Sci U S A. 2001; 98: 10869-10874
        • van't Veer LJ
        • Dai H
        • van de Vrijver MJ
        • et al.
        Gene expression profiling predicts clinical outcome of breast cancer.
        Nature. 2002; 415: 530-536
        • Chan WK
        • Poulsom R
        • Lu QL
        • et al.
        Bcl-2 expression in invasive mammary carcinoma: correlation with apoptosis, hormone receptors, and p53 expression.
        J Pathol. 1993; 169: 138
        • Reed JC
        Balancing cell life and death: bax, apoptosis, and breast cancer.
        J Clin Invest. 1996; 97: 2403-2404
        • Reed JC
        Double identity for proteins of the Bcl-2 family.
        Nature. 1997; 387: 773-776
        • Reed JC
        Dysregulation of apoptosis in cancer.
        J Clin Oncol. 1999; 17: 2941-2953
        • Yang E
        • Korsmeyer SJ
        Molecular thanatopsis: a discourse on the Bcl-2 family and cell death.
        Blood. 1996; 88: 386-401
        • Reed JC
        Bcl-2 family proteins.
        Oncogene. 1998; 17: 3225-3236
        • Kroemer G
        The proto-oncogene Bcl-2 and its role in regulating apoptosis.
        Nat Med. 1997; 3: 614-620
        • Miyashita T
        • Reed JC
        Tumor suppressor p53 is a direct transcriptional activator of the human Bax gene.
        Cell. 1995; 80: 293-299
        • Zhan Q
        • Fan S
        • Bae I
        • et al.
        Induction of Bax by genotoxic stress in human cells correlates with normal p53 status and apoptosis.
        Oncogene. 1994; 9: 3743-3751