J Breast Cancer.  2007 Dec;10(4):258-262. 10.4048/jbc.2007.10.4.258.

Toremifene as an Adjuvant Hormone Therapy for Estrogen Receptor Positive early Breast Cancer: Therapeutic Efficacy and Effect on Endometrium

• Ha HK
• Han W
• Ko E
• Kang SY
• Lee JW
• Cho J
• Jung SY
• Kim EK
• Oh SK
• Youn YK
• Noh DY

• KMID: 2286594
• DOI: http://doi.org/10.4048/jbc.2007.10.4.258

Abstract

PURPOSE: This study was conducted to evaluate the use of toremifene as an adjuvant hormonal therapy for estrogen recepter (ER) positive early breast cancer patients in terms of therapeutic efficacy and effect on endometrium as compared with tamoxifen.
METHODS
Between January 2001 and December 2003, 451 patients with stage 0, I and II breast cancer, received adjuvant hormone therapy that consisted of either tamoxifen (N=387) or toremifene (N=64). The recurrence rate and survival rate were compared between two groups and the incidence of of endometrial event was evaluated in 273 of the patients.
RESULTS
The median follow up period was 57 months and the median hormonal therapy period was 51 months. During the follow up period, there were 3 (2.0%) recurrence in the stage I tamoxifen group, 19 recurrences (8.7%) and 3 deaths (1.4%) in the stage II tamoxifen group (n=219), however there were no instances of recurrence or death in all of the toremifene group. In addition, endometrial cancer developed in 2 patients in the tamoxifen group, but in no patients in toremifene group during the follow up period. Further 21 of the patients who began treatment using tamoxifen changed to toremifene due to adverse side effects. The toremifene was well tolerated by 15 of the patients that changed treatment regimes.
CONCLUSION
Toremifene was found to be as effective and safe as tamoxifen, when used as an adjuvant hormonal therapeutic agent in ER-positive early breast cancer, therefore toremifene may be a good option in place of tamoxifen for patients who are experiencing adverse effects as a result of tamoxifen treatment.

Keyword

Breast cancer; Tamoxifen; Toremifene; Endometrial cancer

MeSH Terms

Breast Neoplasms*
Breast*
Endometrial Neoplasms
Endometrium*
Estrogens*
Female
Follow-Up Studies
Humans
Incidence
Recurrence
Survival Rate
Tamoxifen
Toremifene*
Estrogens
Tamoxifen
Toremifene

Figure

• 

  Fig 1 Disease free survival of tamoxifen and toremifene in stage I (A) and stage II (B).

• 

  Fig 2 Overall survival of tamoxifen and toremifene.

Reference

1. Early Breast Cancer Trialists'Collaborative Group. Tamoxifen for early breast cancer. An overview of the randomized trials. Lancet. 1998. 351:1451–1467.

2. Fisher B, Costantino JP, Wickerham DL, Redmond CK, Kavanah M, Cronin WM, et al. Tamoxifen for prevention of breast cancer: Report of the National Surgical Adjuvant Breast and Bowel Project P-1 study. J Natl Cancer Inst. 1998. 90:1371–1378.

3. Fisher B, Costantino JP, Redmond CK, Fisher ER, Wickerham DL, Cronin WM. Endometrial cancer in tamoxifen-treated breast cancer patients: findings from the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-14. J Natl Cancer Inst. 1994. 86:527–537.

4. Osborne CK. Tamoxifen in the treatment of breast cancer. N Engl J Med. 1998. 339:1609–1618.

5. Pyrhönen S, Valavaara R, Modig H, Pawlicki M, Pienkowski T, Gundersen S, et al. Comparison of toremifene and tamoxifen in postmenopausal patients with advanced breast cancer: a randomized double-blind, the 'nordic' phase III study. Br J Cancer. 1997. 76:270–277.

6. Pagani O, Gelber S, Price K, Zahrieh D, Gelber R, Simoncini E, et al. Toremifene and tamoxifen are equally effective for early-stage breast cancer: first results of International Breast Cancer Study Group Trials 12-93 and 14-93. Ann Oncol. 2004. 15:1749–1759.

7. Shibutani S, Ravindernath A, Terashima I, Suzuki N, Laxmi YR, Kanno Y, et al. Mechanism of lower genotoxicity of toremifene compared with tamoxifen. Cancer Res. 2001. 61:3925–3931.

8. Hard GC, Iatropoulos MJ, Jordan K, Radi L, Kaltenberg OP, Imondi AR, et al. Major difference in the hepatocarcinogenicity and DNA adduct forming ability between toremifene and tamoxifen in female Crl:CD(BR) rats. Cancer Res. 1993. 53:4534–4541.

9. Pyrhönen S, Ellmen J, Vuorinén J, Gershanovich M, Tominaga T, Kaufmann M, et al. Meta-analysis of trials comparing toremifene with tamoxifen and factors predicting outcome of antiestrogen therapy in postmenopausal women with breast cancer. Breast Cancer Res Treat. 1999. 56:133–143.

10. Milla-Santos A, Milla L, Rallo L, Solano V. Phase III randomized trial of toremifene vs tamoxifen in hormonodependant advanced breast cancer. Breast Cancer Res Treat. 2001. 65:119–124.

11. Holli K, Valavaara R, Blanco G, Kataja V, Hietanen P, Flander M, et al. Finnish Breast Cancer Group. Safety and efficacy results of a randomized trial comparing adjuvant toremifene and tamoxifen in postmenopausal patients with node-positive breast cancer. J Clin Oncol. 2000. 18:3487–3494.

12. Harvey HA, Kimura M, Hajba A. Toremifene: an evaluation of its safety profile. Breast. 2006. 15:142–157.

13. Han SH, Yang KH, Kim HY. Comparison of tamoxifen and toremifene as adjuvant treatment in node-negative postmenopausal breast cancer. J Korean Surg Soc. 2002. 63:283–286.

14. Pukkala E, Kyyrönen P, Sankila R, Holli K. Tamoxifen and toremifene treatment of breast cancer and risk of subsequent endometrial cancer: a population-based case-control study. Int J Cancer. 2002. 100:337–341.

15. Park WC, Lee DH, Choi SH, Kim JS, Oh SJ, Jung SS, et al. Two cases of endometrial carcinoma in tamoxifen-treated breast cancer patients in Korea. J Korean Breast Cancer Soc. 2003. 6:196–200.

16. Marttunen MB, Cacciatore B, Hietanen P, Pyrhönen S, Tiitinen A, Wahlström T, et al. Prospective study on gynaecological effects of two antioestrogens tamoxifen and toremifene in postmenopausal women. Br J Cancer. 2001. 84:897–902.

17. Bertelli G, Queirolo P, Vecchio S, Angiolini C, Bergaglio M, Del Mastro L, et al. Toremifene as a substitute for adjuvant tamoxifen in breast cancer patients. Anticancer Res. 2000. 20:3659–3661.