In summary, our comprehensive meta-analysis of all the published studies shows that addition of OFS does not appear to provide any additional benefits beyond those offered by adjuvant tamoxifen alone for premenopausal patients. Higher-risk patients who require chemotherapy might benefit from addition of OFS, but these results should be interpreted with caution because they were based on a smaller sample size and derived from only the SOFT and ZIPP trials. Further, exemestane plus OFS might be a better choice than tamoxifen plus OFS. Additional analyses and follow-up of the four studies might provide further insight into the use of OFS in combination with tamoxifen for the treatment of premenopausal women with early breast cancer.


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This research was supported by a grant from the National Science Foundation of China (81302313).

Shunchao Yan,1 Kai Li,1 Xin Jiao,2 Huawei Zou1

1Department of Oncology, Shengjing Hospital of China Medical University, 2Department of Respiratory Medicine, Shenyang Chest Hospital, Shenyang, People’s Republic of China.


The authors report no conflicts of interest in this work.


1. Siegel RL, Miller KD, Jemal A. Cancer Statistics, 2015. CA Cancer J Clin. 2015;65(1):5–29.

2. American Cancer Society. Breast Cancer Facts and Figures 2013–2014. Available from: Accessed February 11, 2015.

3. Pujol P, Daures JP, Thezenas S, Guilleux F, Rouanet P, Grenier J. Changing estrogen and progesterone receptor patterns in breast carcinoma during the menstrual cycle and menopause. Cancer. 1998;83(4):698–705.

4. Parton M, Dowsett M, Smith I. Studies of apoptosis in breast cancer. BMJ. 2001;322(7301):1528–1532.

5. Osborne CK. Tamoxifen in the treatment of breast cancer. N Engl J Med. 1998;339(22):1609–1618.

6. Klijn JG, Beex LV, Mauriac L, et al. Combined treatment with buserelin and tamoxifen in premenopausal metastatic breast cancer: a randomized study. J Natl Cancer Inst. 2000;92(11):903–911.

7. Mitsuyama S, Nomura Y, Ohno S, et al. [Assessment of goserelin treatment in adjuvant therapy for premenopausal patients with breast cancer in Japan – Zoladex Breast Cancer Study Group Trial-B]. Gan To Kagaku Ryoho. 2005;32(13):2071–2077. Japanese.

8. Baum M, Hackshaw A, Houghton J, et al; ZIPP International Collaborators Group. Adjuvant goserelin in pre-menopausal patients with early breast cancer: Results from the ZIPP study. Eur J Cancer. 2006;42(7):895–904.

9. The Adjuvant Breast Cancer Trials Collaborative Group. Ovarian ablation or suppression in premenopausal early breast cancer: results from the international adjuvant breast cancer ovarian ablation or suppression randomized trial. J Natl Cancer Inst. 2007;99(7):516–525.

10. Cuzick J, Ambroisine L, Davidson N, et al. Use of luteinizing-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. Lancet. 2007;369(9574):1711–1723.

11. Klijn JG, Blamey RW, Boccardo F, et al. Combined tamoxifen and luteinizing hormone-releasing hormone (LHRH) agonist versus LHRH agonist alone in premenopausal advanced breast cancer: a meta-analysis of four randomized trials. J Clin Oncol. 2001;19(2):343–353.

12. Crump M, Sawka CA, DeBoer G, et al. An individual patient-based meta-analysis of tamoxifen versus ovarian ablation as first line endocrine therapy for premenopausal women with metastatic breast cancer. Breast Cancer Res Treat. 1997;44(3):201–210.

13. Dowsett M, Cuzick J, Ingle J, et al. Meta-analysis of breast cancer outcomes in adjuvant trials of aromatase inhibitors versus tamoxifen. J Clin Oncol. 2010;28(3):509–518.

14. Tevaarwerk AJ, Wang M, Zhao F, et al. Phase III comparison of tamoxifen versus tamoxifen plus ovarian function suppression in premenopausal women with node-negative, hormone receptor-positive breast cancer (E-3193, INT-0142): a trial of the Eastern Cooperative Oncology Group. J Clin Oncol. 2014;32(35):3948–3958.

15. Francis PA, Regan MM, Fleming GF. Adjuvant ovarian suppression in premenopausal breast cancer. N Engl J Med. 2015;372(5):436–446.

16. Higgins JPT, Green S, editors. Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0. The Cochrane Collaboration, 2011. Available from: Accessed May 17, 2015.

17. Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002;21(11):1539–1558.

18. Davidson NE, O’Neill AM, Vukov AM, et al. Chemoendocrine therapy for premenopausal women with axillary lymph node-positive, steroid hormone receptor-positive breast cancer: results from INT 0101 (E5188). J Clin Oncol. 2005;23(25):5973–5982.

19. Boccardo F, Rubagotti A, Amoroso D, et al. 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. J Clin Oncol. 2000;18(14):2718–2727.

20. Paridaens RJ, Gelber S, Cole BF, et al. Adjuvant! Online estimation of chemotherapy effectiveness when added to ovarian function suppression plus tamoxifen for premenopausal women with estrogen-receptor-positive breast cancer. Breast Cancer Res Treat. 2010;123(1):303–310.

21. Jakesz R, Hausmaninger H, Kubista E, et al. 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. J Clin Oncol. 2002;20(24):4621–4627.

22. Yang H, Zong X, Yu Y, et al. Combined effects of goserelin and tamoxifen on estradiol level, breast density, and endometrial thickness in premenopausal and perimenopausal women with early-stage hormone receptor-positive breast cancer: a randomised controlled clinical trial. Br J Cancer. 2013;109(3):582–588.

23. Cole MP, Jones CT, Todd ID. A new anti-oestrogenic agent in late breast cancer. An early clinical appraisal of ICI46474. Br J Cancer. 1971;25(2):270–275.

24. Kisanga ER, Gjerde J, Schjøtt J, Mellgren G, Lien EA. Tamoxifen administration and metabolism in nude mice and nude rats. J Steroid Biochem Mol Biol. 2003;84(2–3):361–367.

25. Early Breast Cancer Trialists’ Collaborative Group. Tamoxifen for early breast cancer: an overview of the randomised trials. Lancet. 1998;351(9114):1451–1467.

26. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG); Davies C, Godwin J, Gray R, et al. Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: patient-level meta-analysis of randomised trials. Lancet. 2011;378(9793):771–784.

27. Davies C, Pan H, Godwin J, et al. Adjuvant Tamoxifen: Longer Against Shorter (ATLAS) Collaborative Group. Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trial. Lancet. 2013;381(9869):805–816.

28. Gray RG, Rea D, Handley K, et al. aTTom: Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years in 6,953 women with early breast cancer. J Clin Oncol. 2013;31(18 Suppl):Abstr 5.

29. Schinzinger A. [About breast carcinoma]. Abstract presented at the 18th Congress of the German Society for Surgery. Zentralbl Chir. 1889;16 Suppl:55–66. German.

30. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet. 2005;365(9472):1687–1717.

31. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Systemic treatment of early breast cancer by hormonal, cytotoxic, or immune therapy. 133 randomised trials involving 31000 recurrences and 24000 deaths among 75000 women. Lancet. 1992;339(8784):1–15.

32. Arriagada R, Lê MG, Spielmann M. Randomized trial of adjuvant ovarian suppression in 926 premenopausal patients with early breast cancer treated with adjuvant chemotherapy. Ann Oncol. 2005;16(3):389–396.

33. International Breast Cancer Study Group (IBCSG), Castiglione-Gertsch M, O’Neill A, Price KN, et al. Adjuvant chemotherapy followed by goserelin versus either modality alone for premenopausal lymph node-negative breast cancer: a randomized trial. J Natl Cancer Inst. 2003;95(24):1833–1846.

34. Recchia F, Saggio G, Amiconi G. Gonadotropin-releasing hormone analogues added to adjuvant chemotherapy protect ovarian function and improve clinical outcomes in young women with early breast carcinoma. Cancer. 2006;106(3):514–523.

35. Khan SS, Karn T, Symmans WF. Genomic predictor of residual risk of recurrence after adjuvant chemotherapy and endocrine therapy in high risk estrogen receptor-positive breast cancers. Breast Cancer Res Treat. 2015;149(3):789–797.

36. Arriagada R, Rutqvist LE, Mattsson A, Kramar A, Rotstein S. Adequate locoregional treatment for early breast cancer may prevent secondary dissemination. J Clin Oncol. 1995;13(12):2869–2878.

37. Fortin A, Larochelle M, Laverdière J, Lavertu S, Tremblay D. Local failure is responsible for the decrease in survival for patients with breast cancer treated with conservative surgery and postoperative radiotherapy. J Clin Oncol. 1999;17(1):101–109.

38. Arimidex, Tamoxifen, Alone or in Combination (ATAC) Trialists’ Group, Forbes JF, Cuzick J, Buzdar A, Howell A, Tobias JS, Baum M. Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 100-month analysis of the ATAC trial. Lancet Oncol. 2008;9(1):45–53.

39. Coates AS, Keshaviah A, Thurlimann B, et al. Five years of letrozole compared with tamoxifen as initial adjuvant therapy for postmenopausal women with endocrine-responsive early breast cancer: update of study BIG 1-98. J Clin Oncol. 2007;25(5):486–492.

40. van de Velde CJ, Rea D, Seynaeve C, et al. Adjuvant Tamoxifen and Exemestane in Early Breast Cancer (TEAM): a randomised phase 3 trial. Lancet. 2011;377(9762):321–331.

41. Pagani O, Regan MM, Walley BA, et al; TEXT and SOFT Investigators; International Breast Cancer Study Group. Adjuvant exemestane with ovarian suppression in premenopausal breast cancer. N Engl J Med. 2014;371(2):107–118.

Source: OncoTargets and Therapy.
Originally published on June 12, 2015.