原发性双侧乳腺癌术后转移和死亡风险及其影响因素探讨
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摘要
1目的
探讨原发性双侧乳腺癌术后转移和死亡风险及其影响因素。
2对象和方法
收集天津医科大学附属肿瘤医院1972年3月至2003年12月期间收治的双乳均在本院接受手术治疗的原发性双侧乳腺癌(BPBC)患者222例，并对这些患者的生存和转移状况进行随访。用Kaplan-Meier方法绘制生存曲线和计算生存率，用Kaplan-Meier法和Cox回归进行预后相关因素的分析。
3结果
1．多因素分析发现：第二侧淋巴结阳性、第二侧肿瘤的大小、第一侧淋巴结阳性是影响患者生存结局的主要生存预后因素；第二侧淋巴结阳性、第二侧肿瘤大小、乳腺病史是影响转移结局的预后因素。
2．有乳腺病史、初产年龄＞25岁患者发生转移的可能性大。
3．时间间隔在24个月以内的生存预后较时间间隔在24个月以上的生存预后差。
4．无论第一侧还是第二侧，淋巴结阳性患者的生存和转移预后均较淋巴结阴性患者差，淋巴结阳性组中淋巴结数量＞3个组的预后(死亡和转移)比淋巴结数量≤3个组的预后差。
5．第二侧肿瘤＞5cm的BPBC患者预后(生存和转移)较≤5cm的BPBC患者差。
6．第二侧组织学3级的BPBC患者预后(生存和转移)较组织学1—2级的BPBC患者差。
7．原发性双侧乳腺癌(从第二次手术日起计算生存时间)的3年、5年、10年累计生存率分别为87.04％，78.73％，69.09％，3年、5年、10年累计转移率为14.30％，19.39％，30.53％。
4结论
单因素分析验证了原发性双侧乳腺癌的3个预后影响因素：①第一侧或第二侧的淋巴结阳性(尤其淋巴结数量＞3个)；②第二侧肿瘤＞5cm；③第二侧组织学3级的BPBC患者预后(死亡和转移)差。
多因素分析发现第二侧淋巴结阳性、第二侧肿瘤的大小、第一侧淋巴结阳性是影响BPBC患者生存结局的主要预后因素；第二侧淋巴结阳性、第二侧肿瘤大小、乳腺病史是影响转移结局的主要预后因素。
本研究新的发现有乳腺病史、初产年龄＞25岁对转移预后差，时间间隔在24个月以内的生存预后较时间间隔在24个月以上的生存预后差。
[Objective]
To explore risks of metastasis and death and their related factorsfor postoperative Bilateral Primary Breast Cancer.
[Methods]
222 patients diagnosed with BPBC, received the surgical operationin Tianjin Medical University Cancer Hospital from March 1972 to December2003 were recorded and survival and metastasis status were followed up.Kaplan-Meier method was used for the survival analyses and the same methodand Cox regression were used for the prognostic factors analyses.
[Result]
1. Multivariate analysis finds that size of secondary side cancer andtwo sides positive lymph node are associated with survivalprognosis, secondary side positive lymph node, size of secondaryside cancer and mammary disease history are associated withmetastasis prognosis.
2. The patients with mammary disease history and the age of firstbirth more than 25 years metastasize easily.
3. The patients whose interval between the primary breast cancer andthe second one is less than 24 months have worse survival prognosisthan those more than 24 months.
4. The survival and metastasis prognosis of patients with positivelymph node of anyone side are worse than those with negative lymphnode.
5. The survival and metastasis prognosis of patients with size ofsecondary cancer＞5cm is worse than those with cancer size≤5cm.
6. The survival and metastasis prognosis of patients with histologygrade 3 of secondary cancer is worse than those with histologygrade 1-2.
7. After operation for the secondary cancer of breast, the 3-year5-year and 10-year Cumulative Survival rates of BPBC were 87.04%,78.73% and 69.09%, respectively. The 3-year 5-year and 10-yearCumulative metastasis rates of BPBC were14.30%, 19.39%, 30.53%,respectively.
[Conclusion]
Single factor analyses show that three factors are related to badsurvival and metastasis prognosis which is positive lymph node of twosides, cancer size＞5cm and histology grade 3 of secondary cancer.
Multivariate analysis finds that survival prognosis factors aresize of secondary side cancer and positive lymph node of two sides,metastasis prognosis are positive lymph node of secondary side, cancersize of secondary side and mammary disease history.
The findings that the patients with mammary disease history andwhose first birth age is more than 25 years old have bad metastasisprognosis, and the patients whose interval between the primary breastcancer and the second one is less than 24 months have worse survivalprognosis than those more than 24 months are the first time to be reported.
探讨原发性双侧乳腺癌术后转移和死亡风险及其影响因素。
2对象和方法
收集天津医科大学附属肿瘤医院1972年3月至2003年12月期间收治的双乳均在本院接受手术治疗的原发性双侧乳腺癌(BPBC)患者222例，并对这些患者的生存和转移状况进行随访。用Kaplan-Meier方法绘制生存曲线和计算生存率，用Kaplan-Meier法和Cox回归进行预后相关因素的分析。
3结果
1．多因素分析发现：第二侧淋巴结阳性、第二侧肿瘤的大小、第一侧淋巴结阳性是影响患者生存结局的主要生存预后因素；第二侧淋巴结阳性、第二侧肿瘤大小、乳腺病史是影响转移结局的预后因素。
2．有乳腺病史、初产年龄＞25岁患者发生转移的可能性大。
3．时间间隔在24个月以内的生存预后较时间间隔在24个月以上的生存预后差。
4．无论第一侧还是第二侧，淋巴结阳性患者的生存和转移预后均较淋巴结阴性患者差，淋巴结阳性组中淋巴结数量＞3个组的预后(死亡和转移)比淋巴结数量≤3个组的预后差。
5．第二侧肿瘤＞5cm的BPBC患者预后(生存和转移)较≤5cm的BPBC患者差。
6．第二侧组织学3级的BPBC患者预后(生存和转移)较组织学1—2级的BPBC患者差。
7．原发性双侧乳腺癌(从第二次手术日起计算生存时间)的3年、5年、10年累计生存率分别为87.04％，78.73％，69.09％，3年、5年、10年累计转移率为14.30％，19.39％，30.53％。
4结论
单因素分析验证了原发性双侧乳腺癌的3个预后影响因素：①第一侧或第二侧的淋巴结阳性(尤其淋巴结数量＞3个)；②第二侧肿瘤＞5cm；③第二侧组织学3级的BPBC患者预后(死亡和转移)差。
多因素分析发现第二侧淋巴结阳性、第二侧肿瘤的大小、第一侧淋巴结阳性是影响BPBC患者生存结局的主要预后因素；第二侧淋巴结阳性、第二侧肿瘤大小、乳腺病史是影响转移结局的主要预后因素。
本研究新的发现有乳腺病史、初产年龄＞25岁对转移预后差，时间间隔在24个月以内的生存预后较时间间隔在24个月以上的生存预后差。
[Objective]
To explore risks of metastasis and death and their related factorsfor postoperative Bilateral Primary Breast Cancer.
[Methods]
222 patients diagnosed with BPBC, received the surgical operationin Tianjin Medical University Cancer Hospital from March 1972 to December2003 were recorded and survival and metastasis status were followed up.Kaplan-Meier method was used for the survival analyses and the same methodand Cox regression were used for the prognostic factors analyses.
[Result]
1. Multivariate analysis finds that size of secondary side cancer andtwo sides positive lymph node are associated with survivalprognosis, secondary side positive lymph node, size of secondaryside cancer and mammary disease history are associated withmetastasis prognosis.
2. The patients with mammary disease history and the age of firstbirth more than 25 years metastasize easily.
3. The patients whose interval between the primary breast cancer andthe second one is less than 24 months have worse survival prognosisthan those more than 24 months.
4. The survival and metastasis prognosis of patients with positivelymph node of anyone side are worse than those with negative lymphnode.
5. The survival and metastasis prognosis of patients with size ofsecondary cancer＞5cm is worse than those with cancer size≤5cm.
6. The survival and metastasis prognosis of patients with histologygrade 3 of secondary cancer is worse than those with histologygrade 1-2.
7. After operation for the secondary cancer of breast, the 3-year5-year and 10-year Cumulative Survival rates of BPBC were 87.04%,78.73% and 69.09%, respectively. The 3-year 5-year and 10-yearCumulative metastasis rates of BPBC were14.30%, 19.39%, 30.53%,respectively.
[Conclusion]
Single factor analyses show that three factors are related to badsurvival and metastasis prognosis which is positive lymph node of twosides, cancer size＞5cm and histology grade 3 of secondary cancer.
Multivariate analysis finds that survival prognosis factors aresize of secondary side cancer and positive lymph node of two sides,metastasis prognosis are positive lymph node of secondary side, cancersize of secondary side and mammary disease history.
The findings that the patients with mammary disease history andwhose first birth age is more than 25 years old have bad metastasisprognosis, and the patients whose interval between the primary breastcancer and the second one is less than 24 months have worse survivalprognosis than those more than 24 months are the first time to be reported.
引文
[1] 乳腺癌离我们有多远[EB／OL]．：乳腺普查网，http://www.rxpc.cn.
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[10] 余松林编著．临床随访资料的统计分析方法[M]．人民卫生出版社．第一版，1991年．
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[18] Safal M, Lower EE, Hasselgren PO, et al. Bilateral synchronous breast cancer and Her-2/neu overexpression[J]. Breast Cancer Research and Treatment, 2002, 72 (3): 195.
[19] 王勐．原发性双侧乳腺癌分子水平的研究进展[J]．实用癌症杂志，2004，19(4)：432-433，436．
[20] 洪文善，杨名添，王思愚，等．双侧原发性乳腺癌的预后因素分析[J]．肿瘤防治杂志，2005，12(4)：297-300．
[21] Kinoshita T, Ueda M, Enomoto K,et al. Comparison of p53 gene abnormalities in bilateral and unilateral breast cancer[J]. Cancer, 1995, 76(12):2504-2509.
[22] Healey EA, Cool EF, Oran EJ, et al. Contralateral breast cancer: Clinical characteristics and impact on prognosis[J].J Clin Oncol, 1993, 11 (8):1545--1552.
[23] 毛杰，海健，张超杰，等．双侧原发乳腺癌的流行病学特点与临床分析[J]中国现代医学杂志，2004，14(19)：105-107，110．
[24] 左文述．原发性双侧乳腺癌18例报告[J]．实用肿瘤杂志，1988，(3)：146-148．
[25] Brenner H, Engelsrnann B, Stegrmaoer C, et al. Clinical epidemiology of bilateral breast cancer[J].Cancer, 1993,72(12): 3629-3635.
[26] Awad AT, el-Husseini G, Anwar M, et al. Bilateral primary breast cancer:a clinicopathological study of the second primary [J].Int Surg 1996, 81(1):57-60.
[27] 宁连胜，石松魁，刘素香，等．原发双侧乳腺癌[J]．肿瘤临床，1984，11(2)：96-98．
[28] 沈镇宙，韩企夏，庄传经，等．双侧乳腺癌71例分析[J]．上海医学，1989，12(5)：252-254．
[29] 薛兴欢，马红兵，狄政莉，等．双侧原发性乳腺癌临床分析[J]．中国现代医学杂志，2003，13(24)：11-13，17．
[30] 左怀全，付华，董虹亮，等．双侧乳腺癌22例临床分析[J]．中国肿瘤临床与康复．2002，9(4)：22-23．
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[2] 医药与保健，2006，14(8)-1-1．
[3] 卫生统计年鉴(2005年)[EB／OL]．：中华人民共和国卫生部，http://www.moh.gov.cn.
[4] 卫生统计年鉴(1998年)[EB／OL]．：中华人民共和国卫生部，http://www.moh.gov.cn.
[5] Donovan AJ..Bilateral breast cancer[J].Surg Clin North Am, 1990, 70(10):1141-1149.
[6] Pomerantz RA, Murad T, Hines JR, et al. Bilateral breast cancer[J]. Am Surg, 1989,55(97):441-444.
[7] 阚秀．乳腺癌临床病理学[M]．北京：北京医科大学出版社，1993．98-102．
[8] 刘命文，汝涛，张洪武，等．双侧原发性乳腺癌68例临床分析[J]．南华大学学报：医学版．2003，31(1)：84-85．
[9] 金丕焕主编．医用统计方法[M]．上海医科大学出版社，第一版，1993年．
[10] 余松林编著．临床随访资料的统计分析方法[M]．人民卫生出版社．第一版，1991年．
[11] Rovatti M, Gerosa E, Turi V, et al. Multiple primary malignant neoplasms[J].Minerva Chirugica, 1995,50(11): 949-958.
[12] Guiss L. The problem of bilateral independent mammary carcinoma [J]. Am J Surg, 1954,88(7):171--177.
[13] Farrow J. Bilateral mammary cancer[J].Cancer, 1956,9:1182-1188.
[14] Robbins GF, Berg JW. Bilateral primary breast cancer[J].Cancer, 1964(12),17:1501-1527.
[15] Chaudary MA, Millis RR, Hoskins BOL, et al. Bilateral primary breast cancer[J].A prospective study of disease incidence [J]. Br J Surg, 1984, 71(9) :711--714.
[16] 余科达，狄根红，柳光宇，等．原发性双侧乳腺癌预后分析[J]．实用肿瘤杂志，2006，21(1)：66-69，76．
[17] Heron DE, Komarnicky LT, Hyslop T, et al. Bilateral breast carcinoma: risk factors and outcomes for patients with synchronous and metachronous disease [J]. Cancer, 2000, 88 (12): 2739-2750.
[18] Safal M, Lower EE, Hasselgren PO, et al. Bilateral synchronous breast cancer and Her-2/neu overexpression[J]. Breast Cancer Research and Treatment, 2002, 72 (3): 195.
[19] 王勐．原发性双侧乳腺癌分子水平的研究进展[J]．实用癌症杂志，2004，19(4)：432-433，436．
[20] 洪文善，杨名添，王思愚，等．双侧原发性乳腺癌的预后因素分析[J]．肿瘤防治杂志，2005，12(4)：297-300．
[21] Kinoshita T, Ueda M, Enomoto K,et al. Comparison of p53 gene abnormalities in bilateral and unilateral breast cancer[J]. Cancer, 1995, 76(12):2504-2509.
[22] Healey EA, Cool EF, Oran EJ, et al. Contralateral breast cancer: Clinical characteristics and impact on prognosis[J].J Clin Oncol, 1993, 11 (8):1545--1552.
[23] 毛杰，海健，张超杰，等．双侧原发乳腺癌的流行病学特点与临床分析[J]中国现代医学杂志，2004，14(19)：105-107，110．
[24] 左文述．原发性双侧乳腺癌18例报告[J]．实用肿瘤杂志，1988，(3)：146-148．
[25] Brenner H, Engelsrnann B, Stegrmaoer C, et al. Clinical epidemiology of bilateral breast cancer[J].Cancer, 1993,72(12): 3629-3635.
[26] Awad AT, el-Husseini G, Anwar M, et al. Bilateral primary breast cancer:a clinicopathological study of the second primary [J].Int Surg 1996, 81(1):57-60.
[27] 宁连胜，石松魁，刘素香，等．原发双侧乳腺癌[J]．肿瘤临床，1984，11(2)：96-98．
[28] 沈镇宙，韩企夏，庄传经，等．双侧乳腺癌71例分析[J]．上海医学，1989，12(5)：252-254．
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