作者投稿
专家审稿
编辑办公
邮件订阅
RSS
Correlation between Molecular Subtypes and the Prognosis in Elderly Women with Breast Cancer: A Case-control Study
-
摘要:
目的 通过分析老年乳腺癌分子分型特点, 明确分子分型与老年乳腺癌患者预后的相关性。 方法 回顾性收集北京协和医院乳腺外科2010年1月1日至2016年6月30日收治的老年乳腺癌患者的临床资料, 包括基本人口学特征、手术方式、病理信息、辅助治疗信息及预后。应用Kaplan-Meier和Cox比例风险回归模型分析分子分型与患者无病生存期和总生存期的相关性。 结果 共502例符合纳入和排除标准的患者入选本研究, 平均年龄(76.65±4.36)岁, 其中腔管型乳腺癌占79.88%(401/502), 人表皮生长因子受体-2(human epidermal growth factor receptor 2, Her-2)过表达型乳腺癌占7.77%(39/502), 三阴性乳腺癌占12.35%(62/502)。截至末次随访(2019年4月30日), 8.37%(42/502)的患者出现局部复发和/或远处转移, 50例患者去世, 其中11例死因与乳腺癌相关。生存分析提示, 分子分型与老年女性乳腺癌患者无病生存期(P < 0.001)及总生存期(P=0.040)均显著相关, 腔管B2型(HR=4.306, 95% CI:1.469~12.618, P=0.008)、Her-2过表达型(HR=3.729, 95% CI:1.418~9.809, P=0.008)和三阴性(HR=2.580, 95% CI:1.045~6.367, P=0.040)乳腺癌局部复发和/或远处转移风险均明显高于腔管A型; Her-2过表达型总生存期显著劣于腔管A型(HR=3.219, 95% CI:2.762~3.676, P=0.010)。 结论 老年女性乳腺癌患者的分子分型与无病生存期及总生存期显著相关, 腔管B2型、Her-2过表达型和三阴性老年女性乳腺癌局部复发及远处转移风险较高。 Abstract:Objective The aim of this retrospective study was to analyze the distribution of molecular subtypes and its impact on the prognosis of elderly women with breast cancer(BC). Methods Elderly women with BC who received an operation between January 1st, 2010 and June 30th, 2016 were reviewed. Information on epidemiological characteristics, operation, pathology, adjuvant therapy, and outcome were collected based on the hospital-based database and routine follow-up. Kaplan-Meier analysis and Cox proportional hazards model were applied to pursue the correlation between molecular subtypes and disease-free survival (DFS)/overallsurvival(OS). Results A total of 502 elderly women with BC who met the inclusive and exclusive criteria were enrolled, with an average age of (76.65±4.36)years old, including 401(79.88%) cases of luminal BC, 39(7.77%) of Her-2 rich BC, and 62(12.35%) of triple-negative BC(TNBC). At a median follow-up of 60 months, 8.37%(42/502) of the patients suffered from local recurrence and/or metastasis, and 11 of 50 deaths were of breast cancer. Survival analysis indicated that the molecular subtype had a significant correlation with DFS(P < 0.001) and OS(P=0.040). Compared with the luminal A subgroup, there were more local recurrence or metastasis in the luminal B2(HR=4.306, 95% CI:1.469-12.618, P=0.008), Her-2 rich(HR=3.729, 95% CI:1.418-9.809, P=0.008), and TNBC(HR=2.580, 95% CI:1.045-6.367, P=0.040) subgroups. Compared with the luminal A subgroup, there were more deaths in the Her-2 rich subgroup (HR=3.219, 95% CI:2.762-3.676, P=0.010). Conclusions The molecular subtype has a significant correlation with DFS and OS in elderly women with BC. Luminal B2, Her-2 rich, and TNBC subgroups indicate high risk of local recurrence and distant metastasis. -
Key words:
- elderly /
- breast cancer /
- molecular subtype /
- disease-free survival /
- overall survival
利益冲突 无 -
表 1 不同分子亚型乳腺癌患者临床特点
临床特点 腔管A型
(n=188)腔管B1型
(n=185)腔管B2型
(n=28)Her-2过表达型
(n=39)三阴性
(n=62)P值 年龄(x±s，岁) 76.60±4.34 76.98±4.33 77.04±3.83 75.10±4.29 76.65±4.66 0.183 病理类型[n(%)] ＜0.0001 浸润性导管癌 93(49.47) 136(73.51) 25(89.29) 28(71.79) 51(82.26) 其他类型 95(50.53) 49(26.49) 3(10.71) 11(28.21) 11(17.74) 肿瘤大小(x±s，mm) 19.34±12.56 21.08±10.31 24.39±10.62 26.89±15.43 24.24±10.91 ＜0.0001 分化程度* [n(%)] ＜0.0001 低分化 12(8.11) 39(23.93) 7(25.93) 20(57.14) 35(61.40) 高中分化 136(91.89) 124(76.07) 20(74.07) 15(42.86) 22(38.60) Ki-67(x±s，%) 6.82±3.00 28.05±14.47 32.32±21.02 35.23±21.98 43.39±26.15 ＜0.0001 乳腺手术方式[n(%)] 0.0003 象限切除 141(75.00) 122(65.95) 16(57.14) 15(38.46) 40(64.52) 全乳切除 47(25.00) 63(34.05) 12(42.86) 24(61.54) 22(35.48) 腋窝淋巴结手术方式[n(%)] 0.003 未处理 134(71.28) 113(61.08) 14(50.00) 16(41.03) 38(61.29) 前哨或腋清扫 54(28.72) 72(38.92) 14(50.00) 23(58.97) 24(38.71) 腋窝淋巴结阳性[n(%)] 17(30.48) 29(40.28) 8(57.14) 12(52.17) 13(54.17) 0.158 淋巴血管浸润[n(%)] 4(2.13) 6(3.24) 1(3.57) 2(5.13) 4(6.45) 0.082 *部分患者病理未报告分化程度；Her-2：人表皮生长因子受体-2 
下载: 导出CSV
表 2 不同分子亚型老年女性乳腺癌局部复发和/或远处转移和死亡风险分析
分子分型 局部复发和/或远处转移风险 死亡风险 例数 2年OR(%) 5年OR(%) 例数 2年OR(%) 5年OR(%) 腔管A型(n=188) 5 1.1 2.5 12 2.1 5.8 腔管B1型(n=185) 10 2.7 5.6 16 2.2 10.0 腔管B2型(n=28) 6 17.9 23.3 2 7.1 7.1 Her-2过表达型(n=39) 7 15.4 18.3 8 7.7 11.1 三阴性(n=62) 14 12.9 21.8 12 2.8 16.7 Her-2：同表 1
下载: 导出CSV
表 3 502例乳腺癌患者无病生存期相关因素分析
因素 单因素分析HR(95% CI) P值 多因素分析HR(95% CI) P值 年龄(岁) ＞76比≤76 1.084(1.015~1.158) 0.016 1.063(0.990~1.141) 0.094 肿瘤直径(cm) ＞2比≤2 1.112(0.586~2.110) 0.745 - - 分化程度 低分化比中高分化 1.660(0.648~4.254) 0.291 - - Ki-67(%) 高表达比低表达 1.012(0.998~1.026) 0.091 - - 手术方式 全乳切除比象限切除 0.455(0.215~0.963) 0.039 0.665(0.154~2.865) 0.584 腋窝手术方式 腋窝清扫比前哨淋巴结活检 0.424(0.200~0.898) 0.025 0.467(0.113~1.928) 0.293 脉管瘤栓 阳性比阴性 4.226(1.649~10.829) 0.003 7.168(2.404~21.373) ＜0.001 分子分型(相比腔管A型) 腔管B1型 0.763(0.290~2.007) 0.583 - - 腔管B2型 4.306(1.469~12.618) 0.008 1.493(0.917~2.432) 0.107 Her-2过表达型 3.729(1.418~9.809) 0.008 1.599(1.165~2.194) 0.004 三阴性 2.580(1.045~6.367) 0.040 1.293(1.031~1.622) 0.026 Her-2：同表 1
下载: 导出CSV
表 4 502例乳腺癌患者总生存期相关因素分析
因素 单因素分析HR(95% CI) P值 多因素分析HR(95% CI) P值 年龄(岁) ＞76比≤76 1.082(1.052~1.112) 0.010 1.142(1.113~1.171) ＜0.001 肿瘤直径(cm) ＞2比≤2 2.089(1.789~2.389) 0.014 1.020(0.92~1.120) 0.063 分化程度 低分化比中高分化 1.293(0.881~1.705) 0.534 - - Ki-67(%) 高表达比低表达 1.015(1.009~1.021) 0.016 1.001(0.994~1.008) 0.865 手术方式 全乳切除比象限切除 1.024(0.718~1.330) 0.938 - - 腋窝手术方式 腋窝清扫比前哨淋巴结活检 1.007(0.704~1.310) 0.980 - - 脉管瘤栓 阳性比阴性 1.015(1.009~1.021) 0.016 3.931(3.477~4.385) 0.003 分子分型(相比腔管A型) 腔管B1型 1.339(0.952~1.726) 0.451 - - 腔管B2型 1.227(0.463~1.991) 0.789 - - Her-2过表达型 3.219(2.762~3.676) 0.010 - - 三阴性 0.939(0.367~2.404) 0.895 - - Her-2：同表 1
下载: 导出CSV
-
[1] Jemal A, Ward E, Thun MJ. Recent trends in breast cancer incidence rates by age and tumor characteristics among U.S. women[J]. Breast Cancer Res, 2007, 9:R28. doi: 10.1186/bcr1672 [2] Turner N, Zafarana E, Becheri D, et al. Breast cancer in the elderly:which lessons have we learned?[J].Future Oncol, 2013, 9:1871-1881. doi: 10.2217/fon.13.140 [3] Fan L, Strasser-Weippl K, Li JJ, et al. Breast cancer in China[J]. Lancet Oncol, 2014, 15:e279-e289. doi: 10.1016/S1470-2045(13)70567-9 [4] Kemeny MM, Peterson BL, Kornblith AB, et al. Barriers to clinical trial participation by older women with breast cancer[J]. J Clin Oncol, 2003, 21:2268-2275. doi: 10.1200/JCO.2003.09.124 [5] Aapro MS, Kohne CH, Cohen HJ, et al. Never too old? Age should not be a barrier to enrollment in cancer clinical trials[J]. Oncologist, 2005, 10:198-204. doi: 10.1634/theoncologist.10-3-198 [6] 中国老年乳腺癌治疗共识专家组.中国老年乳腺癌治疗专家共识(2018)[J].协和医学杂志, 2018, 9:307-312. http://d.old.wanfangdata.com.cn/Periodical_zhptwkxwx201801003.aspx [7] Bouchardy C, Rapiti E, Fioretta G, et al. Undertreatment strongly decreases prognosis of breast cancer in elderly women[J]. J Clin Oncol, 2003, 21:3580-3587. doi: 10.1200/JCO.2003.02.046 [8] Yancik R, Wesley MN, Ries LA, et al. Effect of age and comorbidity in postmenopausal breast cancer patients aged 55 years and older[J]. JAMA, 2001, 285:885-892. doi: 10.1001/jama.285.7.885 [9] Biganzoli L, Licitra S, Moretti E, et al. Taxanes in the elderly:can we gain as much and be less toxic?[J]. Crit Rev Oncol Hematol, 2009, 70:262-271. doi: 10.1016/j.critrevonc.2008.07.017 [10] Bergen ES, Tichy C, Berghoff AS, et al. Prognostic impact of breast cancer subtypes in elderly patients[J]. Breast Cancer Res Treat, 2016, 157:91-99. doi: 10.1007/s10549-016-3787-y [11] Jenkins EO, Deal AM, Anders CK, et al. Age-specific changes in intrinsic breast cancer subtypes:a focus on older women[J]. Oncologist, 2014, 19:1076-1083. doi: 10.1634/theoncologist.2014-0184 [12] Perou CM, Sorlie T, Eisen MB, et al. Molecular portraits of human breast tumours[J]. Nature, 2000, 406:747-752. doi: 10.1038/35021093 [13] Nielsen TO, Hsu FD, Jensen K, et al. Immunohistochemical and clinical characterization of the basal-like subtype of invasive breast carcinoma[J]. Clin Cancer Res, 2004, 10:5367-5374. doi: 10.1158/1078-0432.CCR-04-0220 [14] Carey LA, Perou CM, Livasy CA, et al. Race, breast cancer subtypes, and survival in the Carolina Breast Cancer Study[J]. JAMA, 2006, 295:2492-2502. doi: 10.1001/jama.295.21.2492 [15] Valla M, Vatten LJ, Engstrom MJ, et al. Molecular subtypes of breast cancer:long-term incidence trends and prognostic differences[J]. Cancer Epidemiol Biomarkers Prev, 2016, 25:1625-1634. doi: 10.1158/1055-9965.EPI-16-0427 [16] Cheang MC, Chia SK, Voduc D, et al. Ki67 index, HER2 status, and prognosis of patients with luminal B breast cancer[J]. J Natl Cancer Inst, 2009, 101:736-750. doi: 10.1093/jnci/djp082 [17] Cuzick J, Dowsett M, Pineda S, et al. Prognostic value of a combined estrogen receptor, progesterone receptor, Ki-67, and human epidermal growth factor receptor 2 immunohistochemical score and comparison with the Genomic Health recurrence score in early breast cancer[J]. J Clin Oncol, 2011, 29:4273-4278. doi: 10.1200/JCO.2010.31.2835 [18] Ihemelandu CU, Leffall LD, Jr Dewitty RL, et al. Molecular breast cancer subtypes in premenopausal and postmenopausal African-American women:age-specific prevalence and survival[J]. J Surg Res, 2007, 143:109-118. doi: 10.1016/j.jss.2007.03.085 [19] Tavassoli FA, Devilee P. World Health Organization calssificaiton of tumours. Pathology and genetics of tumours of the breast and female genital organs[C]. Lyon: IARC Press, 2003. [20] Lakhani SR, Ellis IO, Sehnitt SJ, et al. WHO classification of tumours of the breast[C]. Lyon: IARC Press, 2012. [21] Ray PS, Bagaria SP, Wang J, et al. Basal-like breast cancer defined by FOXC1 expression offers superior progno-stic value:a retrospective immunohistochemical study[J]. Ann Surg Oncol, 2011, 18:3839-3847. doi: 10.1245/s10434-011-1657-8 [22] Wolff AC, Hammond ME, Schwartz JN, et al. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer[J]. J Clin Oncol, 2007, 25:118-145. http://www.ncbi.nlm.nih.gov/pubmed/17159189 [23] Peto R, Davies C, Godwin J, et al. Comparisons between different polychemotherapy regimens for early breast cancer:meta-analyses of long-term outcome among 100, 000 women in 123 randomised trials[J]. Lancet, 2012, 379:432-444. doi: 10.1016/S0140-6736(11)61625-5 [24] Engstrom MJ, Opdahl S, Hagen AI, et al. Molecular subtypes, histopathological grade and survival in a historic cohort of breast cancer patients[J]. Breast Cancer Res Treat, 2013, 140:463-473. doi: 10.1007/s10549-013-2647-2 [25] Lobbezoo DJ, van Kampen RJ, Voogd AC, et al. Prognosis of metastatic breast cancer subtypes:the hormone receptor/HER2-positive subtype is associated with the most favorable outcome[J]. Breast Cancer Res Treat, 2013, 141:507-514. doi: 10.1007/s10549-013-2711-y [26] Rauh C, Gass P, Eusinger K, et al. Association of molecular subtypes with breast cancer risk factors:a case-only analysis[J]. Eur J Cancer Prev, 2015, 24:484-90. doi: 10.1097/CEJ.0000000000000111 [27] De Kruijf EM, Bastiaannet E, Ruberta F, et al. Comparison of frequencies and prognostic effect of molecular subtypes between young and elderly breast cancer patients[J]. Mol Oncol, 2014, 8:1014-1025. doi: 10.1016/j.molonc.2014.03.022 [28] Schonberg MA, Marcantonio ER, Li D, et al. Breast cancer among the oldest old:tumor characteristics, treatment choices, and survival[J]. J Clin Oncol, 2010, 28:2038-2045. doi: 10.1200/JCO.2009.25.9796 [29] Anderson WF, Katki HA, Rosenberg PS. Incidence of breast cancer in the United States:current and future trends[J]. J Natl Cancer Inst, 2011, 103:1397-1402. doi: 10.1093/jnci/djr257 [30] Freyer G, Braud AC, Chaibi P, et al. Dealing with metastatic breast cancer in elderly women:results from a French study on a large cohort carried out by the 'Obser-vatory on Elderly Patients'[J]. Ann Oncol, 2006, 17:211-216. doi: 10.1093/annonc/mdj043 [31] Elkin EB, Hurria A, Mitra N, et al. Adjuvant chemotherapy and survival in older women with hormone receptor-negative breast cancer:assessing outcome in a population-based, observational cohort[J]. J Clin Oncol, 2006, 24:2757-2764. doi: 10.1200/JCO.2005.03.6053 [32] Giordano SH, Duan Z, Kuo YF, et al. Use and outcomes of adjuvant chemotherapy in older women with breast cancer[J]. J Clin Oncol, 2006, 24:2750-2756. doi: 10.1200/JCO.2005.02.3028 [33] Ring A, Sestak I, Baum M, et al. Influence of comorbidities and age on risk of death without recurrence:a retrospective analysis of the Arimidex, Tamoxifen Alone or in Combination trial[J]. J Clin Oncol, 2011, 29:4266-4272. doi: 10.1200/JCO.2011.35.5545 [34] Muss HB, Woolf S, Berry D, et al. Adjuvant chemotherapy in older and younger women with lymph node-positive breast cancer[J]. JAMA, 2005, 293:1073-1081. doi: 10.1001/jama.293.9.1073 [35] Extermann M, Overcash J, Lyman GH, et al. Comorbidity and functional status are independent in older cancer patients[J]. J Clin Oncol, 1998, 16:1582-1587. doi: 10.1200/JCO.1998.16.4.1582 [36] Monfardini S. Evaluation of renal function in elderly cancer patients[J]. Ann Oncol, 2004, 15:183-184. doi: 10.1093/annonc/mdh078 [37] Land LH, Dalton SO, Jensen MB, et al. Influence of comorbidity on the effect of adjuvant treatment and age in patients with early-stage breast cancer[J]. Br J Cancer, 2012, 107:1901-1907. doi: 10.1038/bjc.2012.472 [38] De Azambuja E, Cardoso F, de Castro G, et al. Ki-67 as prognostic marker in early breast cancer:a meta-analysis of published studies involving 12, 155 patients[J]. Br J Cancer, 2007, 96:1504-1513. doi: 10.1038/sj.bjc.6603756 [39] 张燕娜, 周易冬, 茅枫, 等.孕激素受体与ki-67指数组合对激素受体阳性中分化早期乳腺癌预后的评估价值[J].协和医学杂志, 2019, 10:539-545. http://oldmed.wanfangdata.com.cn/Paper/Detail/PeriodicalPaper_xhyx201905022 [40] Besic N, Besic H, Peric B, et al. Surgical treatment of breast cancer in patients aged 80 years or older-how much is enough?[J]. BMC Cancer, 2014, 14:700. doi: 10.1186/1471-2407-14-700 [41] Van Leeuwen BL, Rosenkranz KM, Feng LL, et al. The effect of under-treatment of breast cancer in women 80 years of age and older[J]. Crit Rev Oncol Hematol, 2011, 79:315-320. doi: 10.1016/j.critrevonc.2010.05.010 -
点击查看大图
图(2) / 表(4)
计量
- 文章访问数: 1041
- HTML全文浏览量: 377
- PDF下载量: 293
- 被引次数: 0
