Journal Article
. 2016 Oct; 48(4):1351-1362.
doi: 10.4143/crt.2015.444.

Survival Outcome of Combined GnRH Agonist and Tamoxifen Is Comparable to That of Sequential Adriamycin and Cyclophosphamide Chemotherapy Plus Tamoxifen in Premenopausal Patients with Lymph-Node-Negative, Hormone-Responsive, HER2-Negative, T1-T2 Breast Cancer

Guiyun Sohn 1 Sei Hyun Ahn 1 Hee Jeong Kim 1 Byung-Ho Son 1 Jong Won Lee 1 Beom Seok Ko 1 Yura Lee 1 Sae Byul Lee 1 Seunghee Baek 2 
  • PMID: 27063654
  •     24 References
  •     4 citations


Purpose: The purpose of this study was to compare treatment outcomes between combined gonadotropin-releasing hormone agonist and tamoxifen (GnRHa+T) and sequential adriamycin and cyclophosphamide chemotherapy and tamoxifen (AC->T) in premenopausal patients with hormone-responsive, lymph-node-negative breast cancer.

Materials And Methods: In total, 994 premenopausal women with T1-T2, lymph-node-negative, hormone-receptor-positive, HER2-negative breast cancer between January 2003 and December 2008 were included in this retrospective cohort study. GnRHa+T and AC->T were administered to 608 patients (61.2%) and 386 patients (38.8%), respectively. Propensity score matching and inverse probability weighting were applied to the original cohort, and 260 patients for each treatment arm were included in the final analysis. Recurrence-free, cancer-specific, and overall survival was compared between the two treatment groups.

Results: A total of 994 patients were followed up for a median of 7.4 years (range, 0.5 to 11.4 years). The 5-year follow-up rate was 98.7%, and 13 patients were lost to follow-up. In propensity-matched cohorts (n=520), there was no difference in recurrence-free, cancer-specific, and overall survival rates between the two treatment groups (p=0.306, p=0.212, and p=0.102, respectively), and this was maintained after applying inverse probability weighting.

Conclusion: GnRHa+T is a reasonable alternative to AC->T in patients with premenopausal, hormone-responsive, HER2-negative, lymph-node-negative, T1-T2 breast cancer.

Keywords: Breast neoplasms; Chemotherapy; Drug therapy; Premenopause; Tamoxifen.

Goserelin versus cyclophosphamide, methotrexate, and fluorouracil as adjuvant therapy in premenopausal patients with node-positive breast cancer: The Zoladex Early Breast Cancer Research Association Study.
W Jonat, M Kaufmann, +14 authors, Zoladex Early Breast Cancer Research Association Study.
J Clin Oncol, 2002 Dec 19; 20(24). PMID: 12488406
Impact of adjuvant therapy on quality of life in women with node-positive operable breast cancer. International Breast Cancer Study Group.
C Hürny, J Bernhard, +9 authors, H J Senn.
Lancet, 1996 May 11; 347(9011). PMID: 8622502
Short term results from GHRH analogue use in pre-menopausal breast cancer in Korea.
H J Kim, J S Lee, +8 authors, S H Ahn.
Eur J Surg Oncol, 2009 Mar 10; 35(9). PMID: 19269125
Quality of life in goserelin-treated versus cyclophosphamide + methotrexate + fluorouracil-treated premenopausal and perimenopausal patients with node-positive, early breast cancer: the Zoladex Early Breast Cancer Research Association Trialists Group.
H de Haes, M Olschewski, +4 authors, Zoladex Early Breast Cancer Research Association Trialists Group.
J Clin Oncol, 2003 Nov 12; 21(24). PMID: 14610048
CMF versus goserelin as adjuvant therapy for node-negative, hormone-receptor-positive breast cancer in premenopausal patients: a randomised trial (GABG trial IV-A-93).
Gunter von Minckwitz, Erika Graf, +8 authors, Manfred Kaufmann.
Eur J Cancer, 2006 Jun 13; 42(12). PMID: 16765589
Prognostic role of amenorrhea induced by adjuvant chemotherapy in premenopausal patients with early breast cancer.
A R Bianco, L Del Mastro, +4 authors, S De Placido.
Br J Cancer, 1991 May 01; 63(5). PMID: 2039706    Free PMC article.
Adjuvant ovarian ablation versus CMF chemotherapy in premenopausal women with pathological stage II breast carcinoma: the Scottish trial. Scottish Cancer Trials Breast Group and ICRF Breast Unit, Guy's Hospital, London.
Lancet, 1993 May 22; 341(8856). PMID: 8098446
Cyclophosphamide, methotrexate, and fluorouracil versus tamoxifen plus ovarian suppression as adjuvant treatment of estrogen receptor-positive pre-/perimenopausal breast cancer patients: results of the Italian Breast Cancer Adjuvant Study Group 02 randomized trial.
F Boccardo, A Rubagotti, +10 authors, A Farris.
J Clin Oncol, 2000 Jul 15; 18(14). PMID: 10894871
Leuprorelin acetate every-3-months depot versus cyclophosphamide, methotrexate, and fluorouracil as adjuvant treatment in premenopausal patients with node-positive breast cancer: the TABLE study.
Peter Schmid, Michael Untch, +8 authors, Kurt Possinger.
J Clin Oncol, 2007 Jun 20; 25(18). PMID: 17577027
Adjuvant ovarian suppression in premenopausal breast cancer.
Prudence A Francis, Meredith M Regan, Gini F Fleming.
N Engl J Med, 2015 Apr 23; 372(17). PMID: 25901437
The magnitude of endocrine effects of adjuvant chemotherapy for premenopausal breast cancer patients. The International Breast Cancer Study Group.
A Goldhirsch, R D Gelber, M Castiglione.
Ann Oncol, 1990 Jan 01; 1(3). PMID: 2261364
Side effects of adjuvant endocrine treatment in premenopausal breast cancer patients: a prospective randomized study.
Marianne Nystedt, Gunilla Berglund, +2 authors, Lars Erik Rutqvist.
J Clin Oncol, 2003 May 02; 21(9). PMID: 12721261
Changing patterns in the clinical characteristics of korean breast cancer from 1996-2010 using an online nationwide breast cancer database.
Beom Seok Ko, Woo Chul Noh, +6 authors, Korean Breast Cancer Society.
J Breast Cancer, 2013 Jan 25; 15(4). PMID: 23346167    Free PMC article.
Survival analyses from the ZEBRA study. goserelin (Zoladex) versus CMF in premenopausal women with node-positive breast cancer.
M Kaufmann, W Jonat, +7 authors, Zoladex Early Breast Cancer Research Association (ZEBRA) Trialists' Group.
Eur J Cancer, 2003 Jul 31; 39(12). PMID: 12888366
Randomized adjuvant trial of tamoxifen and goserelin versus cyclophosphamide, methotrexate, and fluorouracil: evidence for the superiority of treatment with endocrine blockade in premenopausal patients with hormone-responsive breast cancer--Austrian Breast and Colorectal Cancer Study Group Trial 5.
Raimund Jakesz, Hubert Hausmaninger, +13 authors, Austrian Breast and Colorectal Cancer Study Group Trial 5.
J Clin Oncol, 2002 Dec 19; 20(24). PMID: 12488405
A randomized controlled study evaluating safety and efficacy of leuprorelin acetate every-3-months depot for 2 versus 3 or more years with tamoxifen for 5 years as adjuvant treatment in premenopausal patients with endocrine-responsive breast cancer.
Eiichi Shiba, Hiroko Yamashita, +5 authors, Tsukasa Fujimoto.
Breast Cancer, 2015 Feb 07; 23(3). PMID: 25655898    Free PMC article.
Longer therapy, iatrogenic amenorrhea, and survival in early breast cancer.
Sandra M Swain, Jong-Hyeon Jeong, +14 authors, Norman Wolmark.
N Engl J Med, 2010 Jun 04; 362(22). PMID: 20519679    Free PMC article.
Complete hormonal blockade versus epirubicin-based chemotherapy in premenopausal, one to three node-positive, and hormone-receptor positive, early breast cancer patients: 7-year follow-up results of French Adjuvant Study Group 06 randomised trial.
H Roché, P Kerbrat, +8 authors, D Serin.
Ann Oncol, 2006 May 30; 17(8). PMID: 16731539
Adjuvant chemotherapy followed by goserelin versus either modality alone for premenopausal lymph node-negative breast cancer: a randomized trial.
International Breast Cancer Study Group (IBCSG), Monica Castiglione-Gertsch, +7 authors, Richard D Gelber.
J Natl Cancer Inst, 2003 Dec 18; 95(24). PMID: 14679153
Quantifying trade-offs: quality of life and quality-adjusted survival in a randomised trial of chemotherapy in postmenopausal patients with lymph node-negative breast cancer.
J Bernhard, D Zahrieh, +15 authors, C Hürny.
Br J Cancer, 2004 Nov 17; 91(11). PMID: 15545973    Free PMC article.
Adjuvant chemotherapy followed by goserelin compared with either modality alone: the impact on amenorrhea, hot flashes, and quality of life in premenopausal patients--the International Breast Cancer Study Group Trial VIII.
Jürg Bernhard, David Zahrieh, +11 authors, International Breast Cancer Study Group Trial VIII.
J Clin Oncol, 2006 Dec 13; 25(3). PMID: 17159194
Use of luteinising-hormone-releasing hormone agonists as adjuvant treatment in premenopausal patients with hormone-receptor-positive breast cancer: a meta-analysis of individual patient data from randomised adjuvant trials.
LHRH-agonists in Early Breast Cancer Overview group, J Cuzick, +5 authors, R Sainsbury.
Lancet, 2007 May 22; 369(9574). PMID: 17512856
Chemotherapy versus tamoxifen versus chemotherapy plus tamoxifen in node-positive, oestrogen receptor-positive breast cancer patients. Very late results of the 'gruppo di ricerca per la chemio-ormonoterapia adiuvante (GROCTA)' 01-Trial in early breast cancer.
Francesco Boccardo, Pamela Guglielmini, Andrea Parodi, Alessandra Rubagotti.
Breast Cancer Res Treat, 2011 Feb 25; 126(3). PMID: 21347647
Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials.
Early Breast Cancer Trialists' Collaborative Group (EBCTCG).
Lancet, 2005 May 17; 365(9472). PMID: 15894097
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