Toremifene in Postmenopausal Operable Patients with Luminal Subtype of Breast Cancer as Compared with Tamoxifen: A Retrospective Study in China_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

 ZENGYin-duo ¹ , XUFei ² , QINTao ² , YANGYan-hua ² , LIAOYu-ting ² , QINGe ² ,  WANGShu-sen ²

1. Center of Breast Tumor, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 530020, Guangdong province, China;
2. Cancer Center of Sun Yat-sen University, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou 510060, Guangdong province, China;

Corresponding author：

ZENGYin-duo, Email: dr.zengyd@gmail.com

Keywords：

Breast cancer; Luminal; Postmenopausal; Toremifene; Tamoxifen

DOI：

10.7507/1007-9424.20140135

Video：

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Objective To explore the role of toremifene in postmenopausal operable patients with luminal subtype of breast cancer in China. Methods A total of 618 eligible patients diagnosed with luminal subtype of breast cancer from January 2000 to December 2009 in the Cancer Center of Sun Yat-sen University were analyzed. One hundred and fifteen patients were treated with toremifene(toremifene group) and 503 patients were treated with tamoxifen(tamoxifen group) as adjuvant endocrine therapy. Survival was compared by Kaplan-Meier with log-rank test in two groups. Cox analysis was used to compare different prognostic factors. Results The general clinical data had no significant differences between the toremifene group and tamoxifen group (P > 0.05). After a median follow-up of 76 months, there was no statistical difference in the 5-year disease free survival rate and 5-year overall survival rate between the toremifene group and the tamoxifen group (5-year disease free survival rate:78.5% versus 85.5%, P=0.083;5-year overall survival rate:86.4% versus 92.0%, P=0.334). Univariated analysis showed that the histological grade, tumor size, lymph node status, TNM stage, HER-2 positive expression were associated with the disease free survival rate and overall survival rate(P < 0.05). Multivariated analysis showed that the tumor size and lymph node status were the independent risk factors of disease free survival rate and overall survival rate for postmenopausal operable patients with luminal subtype of breast cancer(P < 0.05). HER-2 positive expression was the independent risk factor in predicting disease free survival rate for patients with tamoxifen or toremifene. There was no grade 3 or 4 toxicity for all the patients according to CTC AE 4.0 grade. Conclusions Similar benefit is found in disease free survival rate and overall survival rate in Chinese postmenopausal patients with operable luminal subtype of breast cancer between patients receiving toremifene and tamoxifen with tolerable adverse effects. HER-2 status is associated with disease free survival rate.

Citation： ZENGYin-duo, XUFei, QINTao, YANGYan-hua, LIAOYu-ting, QINGe, WANGShu-sen. Toremifene in Postmenopausal Operable Patients with Luminal Subtype of Breast Cancer as Compared with Tamoxifen: A Retrospective Study in China. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2014, 21(5): 555-561. doi: 10.7507/1007-9424.20140135 Copy

1.	Ward E, Desantis C, Robbins A, et al.Childhood and adolescent cancer statistics, 2014[J].CA Cancer J Clin, 2014, 64(2):83-103.
2.	Theriault RL, Carlson RW, Allred C, et al.Breast cancer, version 3.2013:featured updates to the NCCN guidelines[J].J Natl Compr Canc Netw, 2013, 11(7):753-761.
3.	Decensi A, Sun Z, Guerrieri-Gonzaga A, et al.Bone mineral density and circulating biomarkers in the BIG 1-98 trial comparing adjuvant letrozole, tamoxifen and their sequences[J].Breast Cancer Res Treat, 2014, 144(2):321-329.
4.	Ziller V, Kalder M, Albert US, et al.Adherence to adjuvant endocrine therapy in postmenopausal women with breast cancer[J].Ann Oncol, 2009, 20(3):431-436.
5.	Wärri AM, Huovinen RL, Laine AM, et al.Apoptosis in toremifene-induced growth inhibition of human breast cancer cells in vivo and in vitro[J].J Natl Cancer Inst, 1993, 85(17):1412-1418.
6.	Qin T, Yuan ZY, Peng RJ, et al.Efficacy and tolerability of toremifene and tamoxifen therapy in premenopausal patients with operable breast cancer:a retrospective analysis[J].Curr Oncol, 2013, 20(4):196-204.
7.	Gu R, Jia W, Zeng Y, et al.A comparison of survival outcomes and side effects of toremifene or tamoxifen therapy in premenopausal estrogen and progesterone receptor positive breast cancer patients:a retrospective cohort study[J].BMC Cancer, 2012, 12:161.
8.	Lewis JD, Chagpar AB, Shaughnessy EA, et al.Excellent outcomes with adjuvant toremifene or tamoxifen in early stage breast cancer[J].Cancer, 2010, 116(10):2307-2315.
9.	Murphy LC, Watson P.Steroid receptors in human breast tumorigenesis and breast cancer progression[J].Biomed Pharmacother, 2002, 56(2):65-77.
10.	Ali S, Coombes RC.Endocrine-responsive breast cancer and strategies for combating resistance[J].Nat Rev Cancer, 2002, 2(2):101-112.
11.	Goldhirsch A, Wood WC, Coates AS, et al.Strategies for subtypesdealing with the diversity of breast cancer:highlights of the St.Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2011[J].Ann Oncol, 2011, 22(8):1736-1747.
12.	Shibutani S, Ravindernath A, Suzuki N, et al.Identification of tamoxifen-DNA adducts in the endometrium of women treated with tamoxifen[J].Carcinogenesis, 2000, 21(8):1461-1467.
13.	Kangas L, Nieminen AL, Blanco G, et al.A new triphenylethylene compound, Fc-1157a.Ⅱ.Antitumor effects[J].Cancer Chemother Pharmacol, 1986, 17(2):109-113.
14.	Kallio S, Kangas L, Blanco G, et al.A new triphenylethylene compound, Fc-1157a.I.Hormonal effects[J].Cancer Chemother Pharmacol, 1986, 17(2):103-108.
15.	Shibutani S, Ravindernath A, Terashima I, et al.Mechanism of lower genotoxicity of toremifene compared with tamoxifen[J].Cancer Res, 2001, 61(10):3925-3931.
16.	Hellmann-Blumberg U, Cartner MG, Wurz GT, et al.Intrinsic reactivity of tamoxifen and toremifene metabolites with DNA[J].Breast Cancer Res Treat, 1998, 50(2):135-141.
17.	Holli K, Valavaara R, Blanco G, et al.Safety and efficacy results of a randomized trial comparing adjuvant toremifene and tamoxifen in postmenopausal patients with node-positive breast cancer.Finnish Breast Cancer Group[J].J Clin Oncol, 2000, 18(20):3487-3494.
18.	International Breast Cancer Study G; Pagani O, Gelber S, Price K, et al.Toremifene and tamoxifen are equally effective for earlystage breast cancer:first results of International Breast Cancer Study Group Trials 12-93 and 14-93[J].Ann Oncol, 2004, 15(12):1749-1759.
19.	González-Pérez J, Crespo MJ.Acute effects of toremifene on the vasculature of intact and menopause-induced rats[J].Vascul Pharmacol, 2003, 40(4):205-211.
20.	Tominaga T, Kimijima I, Kimura M, et al.Effects of toremifene and tamoxifen on lipid profiles in post-menopausal patients with early breast cancer:interim results from a Japanese phaseⅢtrial[J].Jpn J Clin Oncol, 2010, 40(7):627-633.
21.	Zhou WB, Ding Q, Chen L, et al.Toremifene is an effective and safe alternative to tamoxifen in adjuvant endocrine therapy for breast cancer:results of four randomized trials[J].Breast Cancer Res Treat, 2011, 128(3):625-631.
22.	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[J].Lancet, 2011, 378(9793):771-784.
23.	Moon YW, Park S, Sohn JH, et al.Clinical significance of progesterone receptor and HER2 status in estrogen receptor-positive, operable breast cancer with adjuvant tamoxifen[J].J Cancer Res Clin Oncol, 2011, 137(7):1123-1130.
24.	Arpino G, Weiss H, Lee AV, et al.Estrogen receptor-positive, progesterone receptor-negative breast cancer:association with growth factor receptor expression and tamoxifen resistance[J].J Natl Cancer Inst, 2005, 97(17):1254-1261.
25.	Regan MM, Neven P, Giobbie-Hurder A, et al.Assessment of letrozole and tamoxifen alone and in sequence for postmenopausal women with steroid hormone receptor-positive breast cancer:the BIG 1-98 randomised clinical trial at 8.1 years median follow-up[J].Lancet Oncol, 2011, 12(12):1101-1108.
26.	De Laurentiis M, Arpino G, Massarelli E, et al.A meta-analysis on the interaction between HER-2 expression and response to endocrine treatment in advanced breast cancer[J].Clin Cancer Res, 2005, 11(13):4741-4748.
27.	Rastelli F, Crispino S.Factors predictive of response to hormone therapy in breast cancer[J].Tumori, 2008, 94(3):370-383.
28.	Pinto AE, André S, Pereira T, et al.C-erbB-2 oncoprotein overexpression identifies a subgroup of estrogen receptor positive (ER+) breast cancer patients with poor prognosis[J].Ann Oncol, 2001, 12(4):525-533.

1. Ward E, Desantis C, Robbins A, et al.Childhood and adolescent cancer statistics, 2014[J].CA Cancer J Clin, 2014, 64(2):83-103.
2. Theriault RL, Carlson RW, Allred C, et al.Breast cancer, version 3.2013:featured updates to the NCCN guidelines[J].J Natl Compr Canc Netw, 2013, 11(7):753-761.
3. Decensi A, Sun Z, Guerrieri-Gonzaga A, et al.Bone mineral density and circulating biomarkers in the BIG 1-98 trial comparing adjuvant letrozole, tamoxifen and their sequences[J].Breast Cancer Res Treat, 2014, 144(2):321-329.
4. Ziller V, Kalder M, Albert US, et al.Adherence to adjuvant endocrine therapy in postmenopausal women with breast cancer[J].Ann Oncol, 2009, 20(3):431-436.
5. Wärri AM, Huovinen RL, Laine AM, et al.Apoptosis in toremifene-induced growth inhibition of human breast cancer cells in vivo and in vitro[J].J Natl Cancer Inst, 1993, 85(17):1412-1418.
6. Qin T, Yuan ZY, Peng RJ, et al.Efficacy and tolerability of toremifene and tamoxifen therapy in premenopausal patients with operable breast cancer:a retrospective analysis[J].Curr Oncol, 2013, 20(4):196-204.
7. Gu R, Jia W, Zeng Y, et al.A comparison of survival outcomes and side effects of toremifene or tamoxifen therapy in premenopausal estrogen and progesterone receptor positive breast cancer patients:a retrospective cohort study[J].BMC Cancer, 2012, 12:161.
8. Lewis JD, Chagpar AB, Shaughnessy EA, et al.Excellent outcomes with adjuvant toremifene or tamoxifen in early stage breast cancer[J].Cancer, 2010, 116(10):2307-2315.
9. Murphy LC, Watson P.Steroid receptors in human breast tumorigenesis and breast cancer progression[J].Biomed Pharmacother, 2002, 56(2):65-77.
10. Ali S, Coombes RC.Endocrine-responsive breast cancer and strategies for combating resistance[J].Nat Rev Cancer, 2002, 2(2):101-112.
11. Goldhirsch A, Wood WC, Coates AS, et al.Strategies for subtypesdealing with the diversity of breast cancer:highlights of the St.Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2011[J].Ann Oncol, 2011, 22(8):1736-1747.
12. Shibutani S, Ravindernath A, Suzuki N, et al.Identification of tamoxifen-DNA adducts in the endometrium of women treated with tamoxifen[J].Carcinogenesis, 2000, 21(8):1461-1467.
13. Kangas L, Nieminen AL, Blanco G, et al.A new triphenylethylene compound, Fc-1157a.Ⅱ.Antitumor effects[J].Cancer Chemother Pharmacol, 1986, 17(2):109-113.
14. Kallio S, Kangas L, Blanco G, et al.A new triphenylethylene compound, Fc-1157a.I.Hormonal effects[J].Cancer Chemother Pharmacol, 1986, 17(2):103-108.
15. Shibutani S, Ravindernath A, Terashima I, et al.Mechanism of lower genotoxicity of toremifene compared with tamoxifen[J].Cancer Res, 2001, 61(10):3925-3931.
16. Hellmann-Blumberg U, Cartner MG, Wurz GT, et al.Intrinsic reactivity of tamoxifen and toremifene metabolites with DNA[J].Breast Cancer Res Treat, 1998, 50(2):135-141.
17. Holli K, Valavaara R, Blanco G, et al.Safety and efficacy results of a randomized trial comparing adjuvant toremifene and tamoxifen in postmenopausal patients with node-positive breast cancer.Finnish Breast Cancer Group[J].J Clin Oncol, 2000, 18(20):3487-3494.
18. International Breast Cancer Study G; Pagani O, Gelber S, Price K, et al.Toremifene and tamoxifen are equally effective for earlystage breast cancer:first results of International Breast Cancer Study Group Trials 12-93 and 14-93[J].Ann Oncol, 2004, 15(12):1749-1759.
19. González-Pérez J, Crespo MJ.Acute effects of toremifene on the vasculature of intact and menopause-induced rats[J].Vascul Pharmacol, 2003, 40(4):205-211.
20. Tominaga T, Kimijima I, Kimura M, et al.Effects of toremifene and tamoxifen on lipid profiles in post-menopausal patients with early breast cancer:interim results from a Japanese phaseⅢtrial[J].Jpn J Clin Oncol, 2010, 40(7):627-633.
21. Zhou WB, Ding Q, Chen L, et al.Toremifene is an effective and safe alternative to tamoxifen in adjuvant endocrine therapy for breast cancer:results of four randomized trials[J].Breast Cancer Res Treat, 2011, 128(3):625-631.
22. 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[J].Lancet, 2011, 378(9793):771-784.
23. Moon YW, Park S, Sohn JH, et al.Clinical significance of progesterone receptor and HER2 status in estrogen receptor-positive, operable breast cancer with adjuvant tamoxifen[J].J Cancer Res Clin Oncol, 2011, 137(7):1123-1130.
24. Arpino G, Weiss H, Lee AV, et al.Estrogen receptor-positive, progesterone receptor-negative breast cancer:association with growth factor receptor expression and tamoxifen resistance[J].J Natl Cancer Inst, 2005, 97(17):1254-1261.
25. Regan MM, Neven P, Giobbie-Hurder A, et al.Assessment of letrozole and tamoxifen alone and in sequence for postmenopausal women with steroid hormone receptor-positive breast cancer:the BIG 1-98 randomised clinical trial at 8.1 years median follow-up[J].Lancet Oncol, 2011, 12(12):1101-1108.
26. De Laurentiis M, Arpino G, Massarelli E, et al.A meta-analysis on the interaction between HER-2 expression and response to endocrine treatment in advanced breast cancer[J].Clin Cancer Res, 2005, 11(13):4741-4748.
27. Rastelli F, Crispino S.Factors predictive of response to hormone therapy in breast cancer[J].Tumori, 2008, 94(3):370-383.
28. Pinto AE, André S, Pereira T, et al.C-erbB-2 oncoprotein overexpression identifies a subgroup of estrogen receptor positive (ER+) breast cancer patients with poor prognosis[J].Ann Oncol, 2001, 12(4):525-533.

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Toremifene in Postmenopausal Operable Patients with Luminal Subtype of Breast Cancer as Compared with Tamoxifen: A Retrospective Study in China

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