Journal Article
. 2010 Apr;15(5).
doi: 10.1634/theoncologist.2009-0150.

Estrogen receptor expression and docetaxel efficacy in patients with metastatic breast cancer: a pooled analysis of four randomized trials

Fabrice Andre 1 Kristine Broglio  Lajos Pusztai  Narjiss Berrada  John R Mackey  Jean Marc Nabholtz  Stephen Chan  Gabriel N Hortobagyi  
  • PMID: 20421265
  •     32 References
  •     1 citations


Background: Differences in the efficacy of various chemotherapies in patients with estrogen receptor (ER)(+) metastatic breast cancer are not well understood. In the present study, we assessed the efficacy of docetaxel in patients with metastatic breast cancer according to ER expression.

Methods: The efficacy of docetaxel in terms of the response rate and progression-free survival (PFS) time was analyzed according to ER expression in four randomized trials comparing a docetaxel-based regimen with a nontaxane regimen that included a total of 1,631 patients. The odds ratio for tumor response was estimated with logistic regression and a hazard ratio (HR) for PFS was estimated with Cox proportional hazards models.

Findings: ER expression was assessable in 1,037 patients included in these trials (64%). ER was expressed in 601 tumors (58%). Docetaxel was associated with a similarly higher response rate in both patients with ER(+) (odds ratio, 2.90; 95% confidence interval [CI], 1.72-4.87) and patients with ER(-) (odds ratio, 2.55; 95% CI, 1.44-4.51) disease. The lower hazard for disease progression with docetaxel was also similar in ER(+) (HR, 0.82; 95% CI, 0.67-1.00) and ER(-) (HR, 0.86; 95% CI, 0.70-1.07) cancers. The effect of docetaxel was not different in ER(+) and ER(-) disease, in terms of both the response rate and PFS time (interaction test, p = .77 and p = .93).

Interpretation: Docetaxel produces a higher response rate and lower risk for disease progression to a statistically similar extent in both patients with ER(+) and patients with ER(-) metastatic breast cancer.

Breast cancer molecular subtypes respond differently to preoperative chemotherapy.
Roman Rouzier, Charles M Perou, +13 authors, Lajos Pusztai.
Clin Cancer Res, 2005 Aug 24; 11(16). PMID: 16115903
Highly Cited.
Breast cancer subtypes and response to docetaxel in node-positive breast cancer: use of an immunohistochemical definition in the BCIRG 001 trial.
Judith Hugh, John Hanson, +11 authors, Charles Vogel.
J Clin Oncol, 2009 Feb 11; 27(8). PMID: 19204205    Free PMC article.
Highly Cited.
Prospective randomized trial of docetaxel versus doxorubicin in patients with metastatic breast cancer.
S Chan, K Friedrichs, +21 authors, 303 Study Group.
J Clin Oncol, 1999 Nov 24; 17(8). PMID: 10561296
Highly Cited.
Factors predicting for efficacy and safety of docetaxel in a compassionate-use cohort of 825 heavily pretreated advanced breast cancer patients.
J Alexandre, P Bleuzen, +11 authors, E Cvitkovic.
J Clin Oncol, 2000 Feb 02; 18(3). PMID: 10653871
New developments in chemotherapy of advanced breast cancer.
D E Lebwohl, R Canetta.
Ann Oncol, 2000 Feb 17; 10 Suppl 6. PMID: 10676565
Systematic reviews of chemotherapy and endocrine therapy in metastatic breast cancer.
M Stockler, N R Wilcken, D Ghersi, R J Simes.
Cancer Treat Rev, 2000 May 18; 26(3). PMID: 10814559
Anastrozole versus tamoxifen as first-line therapy for advanced breast cancer in 668 postmenopausal women: results of the Tamoxifen or Arimidex Randomized Group Efficacy and Tolerability study.
J Bonneterre, B Thürlimann, +7 authors, M von Euler.
J Clin Oncol, 2000 Nov 15; 18(22). PMID: 11078487
Highly Cited.
Polychemotherapy for early breast cancer: an overview of the randomised clinical trials with quality-adjusted survival analysis.
B F Cole, R D Gelber, +2 authors, A Goldhirsch.
Lancet, 2001 Aug 11; 358(9278). PMID: 11498214
Anastrozole is superior to tamoxifen as first-line therapy in hormone receptor positive advanced breast carcinoma.
J Bonneterre, A Buzdar, +8 authors, Investigators Committee Members.
Cancer, 2001 Dec 18; 92(9). PMID: 11745278
Assessment of molecular markers of clinical sensitivity to single-agent taxane therapy for metastatic breast cancer.
Catherine Van Poznak, Lee Tan, +4 authors, Andrew D Seidman.
J Clin Oncol, 2002 May 01; 20(9). PMID: 11981003
Are anthracycline-taxane regimens the new standard of care in the treatment of metastatic breast cancer?
Vicente Valero, Gabriel N Hortobagyi.
J Clin Oncol, 2003 Mar 15; 21(6). PMID: 12637456
Docetaxel and doxorubicin compared with doxorubicin and cyclophosphamide as first-line chemotherapy for metastatic breast cancer: results of a randomized, multicenter, phase III trial.
Jean-Marc Nabholtz, Carla Falkson, +15 authors, TAX 306 Study Group.
J Clin Oncol, 2003 Mar 15; 21(6). PMID: 12637459
Overall survival is not a realistic end point for clinical trials of new drugs in advanced solid tumors: a critical assessment based on recently reported phase III trials in colorectal and breast cancer.
Angelo Di Leo, Harry Bleiberg, Marc Buyse.
J Clin Oncol, 2003 May 14; 21(10). PMID: 12743164
Phase III study of letrozole versus tamoxifen as first-line therapy of advanced breast cancer in postmenopausal women: analysis of survival and update of efficacy from the International Letrozole Breast Cancer Group.
Henning Mouridsen, Mikhail Gershanovich, +17 authors, Ajay Bhatnagar.
J Clin Oncol, 2003 May 31; 21(11). PMID: 12775735
Highly Cited.
The effect on tumor response of adding sequential preoperative docetaxel to preoperative doxorubicin and cyclophosphamide: preliminary results from National Surgical Adjuvant Breast and Bowel Project Protocol B-27.
Harry D Bear, Stewart Anderson, +9 authors, National Surgical Adjuvant Breast and Bowel Project Protocol B-27.
J Clin Oncol, 2003 Oct 16; 21(22). PMID: 14559892
Highly Cited.
Breast cancer with synchronous metastases: trends in survival during a 14-year period.
Fabrice Andre, Khemaies Slimane, +9 authors, Marc Spielmann.
J Clin Oncol, 2004 Aug 18; 22(16). PMID: 15310773
Reporting results of cancer treatment.
A B Miller, B Hoogstraten, M Staquet, A Winkler.
Cancer, 1981 Jan 01; 47(1). PMID: 7459811
Highly Cited.
A randomized multicenter trial comparing mitoxantrone, cyclophosphamide, and fluorouracil with doxorubicin, cyclophosphamide, and fluorouracil in the therapy of metastatic breast carcinoma.
J M Bennett, H B Muss, +6 authors, I Schoch.
J Clin Oncol, 1988 Oct 01; 6(10). PMID: 3049953
Differential response to chemotherapy in metastatic breast cancer in relation to estrogen receptor level. Results of a prospective randomized study.
D Rosner, W W Lane, T Nemoto.
Cancer, 1989 Jul 01; 64(1). PMID: 2731120
A multivariate analysis of tumour biological factors predicting response to cytotoxic treatment in advanced breast cancer.
J Sjöström, S Krajewski, +5 authors, C Blomqvist.
Br J Cancer, 1998 Sep 22; 78(6). PMID: 9743306    Free PMC article.
Prospective randomized trial of docetaxel versus mitomycin plus vinblastine in patients with metastatic breast cancer progressing despite previous anthracycline-containing chemotherapy. 304 Study Group.
J M Nabholtz, H J Senn, +22 authors, M Aapro.
J Clin Oncol, 1999 May 20; 17(5). PMID: 10334526
ESMO Minimum Clinical Recommendations for diagnosis, treatment and follow-up of locally recurrent or metastatic breast cancer (MBC).
V V Kataja, M Colleoni, J Bergh, ESMO Guidelines Task Force.
Ann Oncol, 2005 May 13; 16 Suppl 1. PMID: 15888735
Randomized phase II trial of the efficacy and safety of trastuzumab combined with docetaxel in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer administered as first-line treatment: the M77001 study group.
Michel Marty, Francesco Cognetti, +14 authors, Jean-Marc Extra.
J Clin Oncol, 2005 May 25; 23(19). PMID: 15911866
Highly Cited.
Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor-positive breast cancer.
Soonmyung Paik, Gong Tang, +11 authors, Norman Wolmark.
J Clin Oncol, 2006 May 25; 24(23). PMID: 16720680
Highly Cited.
Pharmacogenomic predictor of sensitivity to preoperative chemotherapy with paclitaxel and fluorouracil, doxorubicin, and cyclophosphamide in breast cancer.
Kenneth R Hess, Keith Anderson, +14 authors, Lajos Pusztai.
J Clin Oncol, 2006 Aug 10; 24(26). PMID: 16896004
Highly Cited.
Second consensus on medical treatment of metastatic breast cancer.
S Beslija, J Bonneterre, +20 authors, H Zwierzina.
Ann Oncol, 2006 Jul 13; 18(2). PMID: 16831851
Molecular subtypes of breast cancer in relation to paclitaxel response and outcomes in women with metastatic disease: results from CALGB 9342.
Lyndsay N Harris, Gloria Broadwater, +10 authors, Lynn Dressler.
Breast Cancer Res, 2006 Nov 30; 8(6). PMID: 17129383    Free PMC article.
Polychemotherapy for early breast cancer: results from the international adjuvant breast cancer chemotherapy randomized trial.
Adjuvant Breast Cancer Trials Collaborative Group.
J Natl Cancer Inst, 2007 Apr 05; 99(7). PMID: 17405995
Evaluation of biological pathways involved in chemotherapy response in breast cancer.
Attila Tordai, Jing Wang, +6 authors, Lajos Pusztai.
Breast Cancer Res, 2008 May 01; 10(2). PMID: 18445275    Free PMC article.
Estrogen receptor expression and efficacy of docetaxel-containing adjuvant chemotherapy in patients with node-positive breast cancer: results from a pooled analysis.
Fabrice Andre, Kristine Broglio, +5 authors, Lajos Pusztai.
J Clin Oncol, 2008 May 30; 26(16). PMID: 18509176
Effect of molecular disease subsets on disease-free survival in randomized adjuvant chemotherapy trials for estrogen receptor-positive breast cancer.
Lajos Pusztai, Kristine Broglio, +3 authors, Gabriel N Hortobagyi.
J Clin Oncol, 2008 Jul 30; 26(28). PMID: 18662965
Meeting highlights: international expert consensus on the primary therapy of early breast cancer 2005.
A Goldhirsch, J H Glick, +4 authors, Panel members.
Ann Oncol, 2005 Sep 09; 16(10). PMID: 16148022
Highly Cited.
Estradiol promotes the progression of ER+ breast cancer through methylation-mediated RSK4 inactivation.
Qiuyun Li, Hui Gao, +2 authors, Yi Jiang.
Onco Targets Ther, 2019 Aug 16; 12. PMID: 31413588    Free PMC article.