Influence of Estrogen on Zoledronic Acid in Preventing Bone Metastasis of Breast Cancer_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

 WANGYong-gao ,  Dilimulati-Aisimutula , LUANMei-xiang , Adilijiang-Maimaitiming

Department of Breast Surgery, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, Xinjiang Uygur Autonomous Region, China;

Corresponding author：

Dilimulati-Aisimutula, Email: 2499156828@qq.com

Keywords：

Breast cancer; Bone metastasis; Estrogen; Zoledronate acid

DOI：

10.7507/1007-9424.20140138

Video：

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Objective To study the influence of estrogen on zoledronic acid in preventing bone metastasis of breast cancer. Methods Two hundred and sixteen breast cancer patients who accepted modified radical mastectomy, chemotherapy, and the prophylaxis of zoledronate acid from January 2006 to December 2009 in this hospital were collected, including luminal A 55 cases, luminal B 63 cases, HER-2 positive 50 cases, triple negative 48 cases. Then these patients were categorized into low estrogen group(n=39) and normal estrogen group(n=177) according to the estrogen level. The patients in the low estrogen group accepted drug induced menopause, in the normal estrogen group didn't accept drug induced menopause. All the patients accepted the therapy of zoledronate acid, then with clinical follow-up for 3-5 years until progressive disease(include neoplasm recurrence, bone metastasis, and other neoplasm metastasis etc.). Results The rate of bone metastasis in the low estrogen group was significantly lower than that in the normal estrogen group (χ²=21.91, P < 0.05). For the patients with luminal A, luminal B, HER-2 positive, and triple negative, the rates of bone metastases in the low estrogen group were significantly lower than those in the normal estrogen group[luminal A:5.13%(2/39) versus 12.43%(22/177), χ²=4.54, P < 0.05;luminal B:7.69%(3/39) versus 13.56%(24/177), χ²=6.04, P < 0.05;HER-2 postive:2.56%(1/39) versus 15.25%(27/177), χ²=3.95, P < 0.05;triple negative:2.56% (1/39) versus 18.08%(32/177), P < 0.05]. The rate of bone metastasis among the different subtype of breast cancer in the low estrogen group was not significant difference(χ²=0.55, P > 0.05). Conclusions From the limited preliminary data, the premenopausal women patients with breast cancer who accepted drug induced menopause afer application of zoledronate acid for preverttion of bone metastasis has a obviously efficacy, and the efficacy has no difference among four molecular subtypes of breast cancer.

Citation： WANGYong-gao, Dilimulati-Aisimutula, LUANMei-xiang, Adilijiang-Maimaitiming. Influence of Estrogen on Zoledronic Acid in Preventing Bone Metastasis of Breast Cancer. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2014, 21(5): 572-576. doi: 10.7507/1007-9424.20140138 Copy

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2.	Gruver AM, Portier BP, Tubbs RR.Molecular pathology of breast cancer:the journey from traditional practice toward embracing the complexity of a molecular classification[J].Arch Pathol Lab Med, 2011, 135(5):544-557.
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5.	Mundy GR.Metastasis to bone:causes, consequences and therapeutic opportunities[J].Nat Rev Cancer, 2002, 2(8):584-593.
6.	Scheid V, Buzdar AU, Smith TL, et al.Clinical course of breast cancer patients with osseous metastasis treated with combination chemotherapy[J].Cancer, 1986, 58(12):2589-2593.
7.	Fox EM, Andrade J, Shupnik MA.Novel actions of estrogen to promote proliferation:Integration of cytoplasmic and nuclear pathways[J].Steroids, 2009, 74(7):622-627.
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10.	Rogers MJ, Gordon S, Benford HL, et al.Cellular and molecular mechanisms of action of bisphosphonates[J].Cancer, 2000, 88(12 Suppl):2961-2978.
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13.	Pike MC, Spicer DV, Dahmoush L, et al.Estrogens, progestogens, normal breast cell proliferation, and breast cancer risk[J].Epidemiol Rev, 1993, 15(1):17-35.
14.	Clemons M, Goss P.Estrogen and the risk of breast cancer[J].N Engl J Med, 2001, 344(4):276-285.
15.	Clarke R, Leonessa F, Welch JN, et al.Cellular and molecular pharmacology of antiestrogen action and resistance[J].Pharmacol Rev, 2001, 53(1):25-71.
16.	Clarke RB, Howell A, Potten CS, et al.Dissociation between steroid receptor expression and cell proliferation in the human breast[J].Cancer, 1997, 57(22):4987-4991.
17.	Russo J, Ao X, Grill C, et al.Pattern of distribution of cells positive for estrogen receptor alpha and progesterone receptor in relation to proliferating cells in the mammary gland[J].Breast Cancer, 1999, 53(3):217-227.
18.	Seagroves TN, Lydon JP, Hovey RC, et al.C/EBPbeta (CCAAT/enhancer binding protein) controls cell fate determination during mammary gland development[J].Mol Endocrinol, 2000, 14(3):359-368.
19.	林颖.双膦酸盐临床试验最新进展--2011年SABCS会议速递[J].药品评价, 2012, 9(6):24-25.
20.	邵志敏, 沈镇宙, 徐兵河, 等.乳腺肿瘤学[M].上海:复旦大学出版社, 2013:474-478.
21.	Coleman R, Marshall H, Gregory W, et al.5019 poster discussion discordant treatment effects according to menopausal status following adjuvant zoledronic acid in stageⅡ/Ⅲbreast cancer.The AZURE trial (BIG 01/04)[J].Eur J Cancer, 2011, 47(1):s336.
22.	邵淑丽, 李秀云, 杨金存, 等.女性性腺激素水平与乳腺疾病的相关性研究[J].医学检验与临床, 2009, 20(1):21-23.
23.	Schenk R, Eggli P, Fleisch H, et al.Quantitative morphometric evaluation of the inhibitory activity of new aminobisphosphonates on bone resorption in the rat[J].Calcif Tissue Int, 1986, 38(6):342-349.
24.	Russell RG, Xia Z, Dunford JE, et al.Bisphosphonates:an update on mechanisms of action and how these relate to clinical efficacy[J].Ann N Y Acad Sci, 2007, 1117:209-257.

1. Fang M, Toher J, Morgan M, et al.Genomic differences between estrogen receptor (ER)-positive and ER-negative human breast carcinoma identified by single nucleotide polymorphism array comparative genome hybridization analysis[J].Cancer, 2011, 117(10):2024-2034.
2. Gruver AM, Portier BP, Tubbs RR.Molecular pathology of breast cancer:the journey from traditional practice toward embracing the complexity of a molecular classification[J].Arch Pathol Lab Med, 2011, 135(5):544-557.
3. Coleman RE, Rubens RD.The clinical course of bone metastases from breast cancer[J].Br J Cancer, 1987, 55(1):61-66.
4. Jemal A, Bray F, Center MM, et al.Global cancer statistics[J].CA Cancer J Clin, 2011, 61(2):69-90.
5. Mundy GR.Metastasis to bone:causes, consequences and therapeutic opportunities[J].Nat Rev Cancer, 2002, 2(8):584-593.
6. Scheid V, Buzdar AU, Smith TL, et al.Clinical course of breast cancer patients with osseous metastasis treated with combination chemotherapy[J].Cancer, 1986, 58(12):2589-2593.
7. Fox EM, Andrade J, Shupnik MA.Novel actions of estrogen to promote proliferation:Integration of cytoplasmic and nuclear pathways[J].Steroids, 2009, 74(7):622-627.
8. 孙燕, 石远凯.临床肿瘤内科手册[M].第5版.北京:人民卫生出版社, 2007:920-921.
9. Goldhirsch A, Wood WC, Coates AS, et al.Strategies for subtypes-dealing 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.
10. Rogers MJ, Gordon S, Benford HL, et al.Cellular and molecular mechanisms of action of bisphosphonates[J].Cancer, 2000, 88(12 Suppl):2961-2978.
11. Selander K, Lehenkari P, Väänänen HK.The effects of bisphosphonates on the resorption cycle of isolated osteoclasts[J].Calcif Tissue Int, 1994, 55(5):368-375.
12. Murakami H, Takahashi N, Sasaki T, et al.A possible mechanism of the specific action of bisphosphonates on osteoclasts:tiludronate preferentially affects polarized osteoclasts having ruffled borders[J].Bone, 1995, 17(2):137-144.
13. Pike MC, Spicer DV, Dahmoush L, et al.Estrogens, progestogens, normal breast cell proliferation, and breast cancer risk[J].Epidemiol Rev, 1993, 15(1):17-35.
14. Clemons M, Goss P.Estrogen and the risk of breast cancer[J].N Engl J Med, 2001, 344(4):276-285.
15. Clarke R, Leonessa F, Welch JN, et al.Cellular and molecular pharmacology of antiestrogen action and resistance[J].Pharmacol Rev, 2001, 53(1):25-71.
16. Clarke RB, Howell A, Potten CS, et al.Dissociation between steroid receptor expression and cell proliferation in the human breast[J].Cancer, 1997, 57(22):4987-4991.
17. Russo J, Ao X, Grill C, et al.Pattern of distribution of cells positive for estrogen receptor alpha and progesterone receptor in relation to proliferating cells in the mammary gland[J].Breast Cancer, 1999, 53(3):217-227.
18. Seagroves TN, Lydon JP, Hovey RC, et al.C/EBPbeta (CCAAT/enhancer binding protein) controls cell fate determination during mammary gland development[J].Mol Endocrinol, 2000, 14(3):359-368.
19. 林颖.双膦酸盐临床试验最新进展--2011年SABCS会议速递[J].药品评价, 2012, 9(6):24-25.
20. 邵志敏, 沈镇宙, 徐兵河, 等.乳腺肿瘤学[M].上海:复旦大学出版社, 2013:474-478.
21. Coleman R, Marshall H, Gregory W, et al.5019 poster discussion discordant treatment effects according to menopausal status following adjuvant zoledronic acid in stageⅡ/Ⅲbreast cancer.The AZURE trial (BIG 01/04)[J].Eur J Cancer, 2011, 47(1):s336.
22. 邵淑丽, 李秀云, 杨金存, 等.女性性腺激素水平与乳腺疾病的相关性研究[J].医学检验与临床, 2009, 20(1):21-23.
23. Schenk R, Eggli P, Fleisch H, et al.Quantitative morphometric evaluation of the inhibitory activity of new aminobisphosphonates on bone resorption in the rat[J].Calcif Tissue Int, 1986, 38(6):342-349.
24. Russell RG, Xia Z, Dunford JE, et al.Bisphosphonates:an update on mechanisms of action and how these relate to clinical efficacy[J].Ann N Y Acad Sci, 2007, 1117:209-257.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Influence of Estrogen on Zoledronic Acid in Preventing Bone Metastasis of Breast Cancer

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