1、20222022年乳腺癌内科治疗进展年乳腺癌内科治疗进展 贾存东贾存东 新疆医科大学肿瘤医院内三科新疆医科大学肿瘤医院内三科 Cancer from breast From duct and lobule Invasive ductal carcinoma(IDC)Invasive lobular carcinoma Others From stroma:sarcoma(Phyllodes)Squamous cell carcinoma Lymphoma Normal Breast A.Breast Duct System B.Lobules C.Breast Duct System D.Ni
2、pple E.Fat F.Chest Muscle G.Ribs A.Cells lining duct B.Basement membrane C.Open central duct Invasive ductal carcinoma(IDC)A.Breast Duct System B.Lobules C.Breast Duct System D.Nipple E.Fat F.Chest Muscle G.Ribs A.Cells lining duct B.Cancer cells,breaking through the basement membrane C.Basement mem
3、brane Ductal carcinoma in situ(DCIS)A.Breast Duct System B.Lobules C.Breast Duct System D.Nipple E.Fat F.Chest Muscle G.Ribs A.Cells lining duct B.Extra cancer like cells,but aaacontained within duct C.Intact basement membrane D.Open central duct Invasive lobular carcinoma(ILC)A.Breast Duct System B
4、.Lobules C.Breast Duct System D.Nipple E.Fat F.Chest Muscle G.Ribs A.Cells lining lobule B.Cancer cells,breaking through the basement membrane.C.Basement membrane 全球乳腺癌发病概况 乳腺癌：是全世界最常见的女性肿瘤乳腺癌：是全世界最常见的女性肿瘤 2002年年,全球约全球约 1,151,298 新发乳腺癌病例被确诊；新发乳腺癌病例被确诊；410,712 人死于乳腺癌人死于乳腺癌每小时因乳腺癌死亡每小时因乳腺癌死亡48人人 Breas
5、t Carcinoma Worldwide Jemal et al.CA Cancer J Clin.2022;61:69 中国乳腺癌发病概况 每年约有每年约有20多万新发乳腺癌病例多万新发乳腺癌病例 2002年全国乳腺癌年龄标化发病率年全国乳腺癌年龄标化发病率:18.7/100,000；死亡率死亡率:5.5/100,000 发病率：城市发病率：城市农村农村 高发年龄段：高发年龄段：4550岁岁 京津沪乳腺癌发病率增长趋势 每100,000人 上海 北京 天津 80年代*21.5 22.4 21.2 90年代*30.1 27.8 25.5 2000年*56.2 43.8 42.25 x李连弟，
6、饶克勤，中国市、县恶性肿瘤李连弟，饶克勤，中国市、县恶性肿瘤的发病与死亡，北京：中国医药科技出的发病与死亡，北京：中国医药科技出版社，版社，2001：26 x x 乳腺癌居京津沪女性恶性肿瘤发病首乳腺癌居京津沪女性恶性肿瘤发病首位位 首都医药首都医药 2022，7：36-8 乳腺癌的乳腺癌的概述概述 乳腺癌是一种全身性的疾病乳腺癌是一种全身性的疾病，即使早期乳腺即使早期乳腺癌也可能出现全身播散癌也可能出现全身播散。因此因此，手术范围逐步缩手术范围逐步缩小小，全身治疗越来越受到重视全身治疗越来越受到重视。乳腺癌的发病原因乳腺癌的发病原因 遗传因素遗传因素5-10%为遗传性为遗传性 40%遗传性乳
7、腺癌由遗传性乳腺癌由BRCA1和和BRCA2突变引突变引起。起。乳腺暴露在雌激素的时间延长乳腺暴露在雌激素的时间延长 初潮早，绝经晚，绝经后长时间补充雌激素初潮早，绝经晚，绝经后长时间补充雌激素 拒绝生育，哺乳，初产年龄拒绝生育，哺乳，初产年龄35岁岁 肥胖肥胖 高脂饮食高脂饮食 环境因素环境因素 接触放射物质，化学致癌物质等。接触放射物质，化学致癌物质等。How Do We Assess Risk in Breast Cancer Patients Classic Pathological Criteria Oncotype DX New tools in the Genomic Era A
8、ge Tumor Size Lymph Node Status ER/PR HER2 Tumor Grade Adjuvant!Computer-based model 乳腺癌的分型乳腺癌的分型 Genomics of Breast Cancer:Breast Cancer is NOT One Disease!Luminal Subtype A Luminal Subtype B HER-2+Basal Subtype Normal Breastlike Sorlie et al,Proc Natl Acad Sci 100:8418,2003 Subtypes vary with resp
9、ect to:Likelihood of recurrence Sites of metastases Response to treatment Figure 1a.Sorlie T,Tibshirani R,Parker J,et al:Repeated observation of breast tumor subtypes in independent gene expression data sets.Proc Natl Acad Sci U S A 100:8418-23,2003 Sotiriou,C.et al.NEJM,2022.Luminal A Luminal B HER
10、2+Basal-like Intrinsic Breast Cancer Subtypes described by Perou et al.Express amounts Of luminal cyto-Keratins&genetic Markers of luminal Epithelial cells of Normal tissue Express levels of EGFR,c-kit,&growth factors like hepatocyte growth factor and IGF Subtypes and Prognosis Sorlie T et al,PNAS 2
11、001 The 21-gene Recurrence Score:Oncotype DX Levels of Gene Expression Determine Recurrence Score 21-gene assay=16 outcome-related genes+5 reference genes Higher expression levels of“favorable genes=RS Higher expression levels of“unfavorable genes=RS A risk score is calculated from 0-100 Cutoff poin
12、ts chosen based on Results of NSABP trial B-20 Sparano,J&Paik,S.JCO,2022.Prospective Validation Study of 21-Gene Assay Analyzed tumor blocks of 668 patients on NSABP trial B-14 study that were randomized to tamoxifen RS was significantly correlated with relapse free interval&OS(p0.001)Rate of distan
13、t recurrence at 10 years:Low risk 6.8%Intermediate risk 14.3%High risk 30.5%(similar risk to LN+patients)No distant recurrence (low risk)=93.2%No distant recurrence (high risk)=69.5%p0.001 Paik,S.JCO,2004.Recurrence Score 40 35 30 25 20 15 10 5 0 0 5 10 15 20 25 30 35 40 45 50 Recurrence Score Rate
14、of Distant Recurrence at 10 years 95%C.I.Recurrence Rate Low RS 18 Rec.Rate=6.8%C.I.=4.0%-9.6%Intermediate RS 18-31 Rec.Rate=14.3%C.I.=8.3%-20.3%High RS 31 Rec.Rate=30.5%C.I.=23.6%-37.4%Paik S.et al.N Engl J Med 2004;351:2817-26 Other End Points RS predicted distant recurrence independent of age&tum
15、or size The likelihood of distant recurrence continuously as the RS Multivariate Cox Analysis Distant Recurrence as a Function of RS Paik,S.JCO,2004.Kaplan-Meier Plots for Distant Recurrence All patients Low Risk RS 18 Intermediate Risk RS 18-30 High Risk RS 31 88%60%92.2%87.7%Paik,S.JCO,2022.乳癌的综合治
16、疗治疗手段乳癌的综合治疗治疗手段 放射治疗放射治疗 外科手术外科手术 内分泌治疗内分泌治疗 化学治疗化学治疗 分子靶向治疗分子靶向治疗 各期乳腺癌治疗原那么 I期：手术治疗改进根治或保乳手术，目期：手术治疗改进根治或保乳手术，目前趋向保乳放疗。对高危病人可考虑术后化前趋向保乳放疗。对高危病人可考虑术后化疗疗 II期：先手术，术后化疗，选择性放疗。期：先手术，术后化疗，选择性放疗。III期：一般先行化疗，然后手术，术后化、放期：一般先行化疗，然后手术，术后化、放疗。疗。以上各期病人，如果受体阳性，那么在化以上各期病人，如果受体阳性，那么在化放疗结束后给予内分泌治疗放疗结束后给予内分泌治疗 IV期：采用化疗和内分泌治疗为主的综合治疗期：采用化疗和内分泌治疗为主的综合治疗 一、乳腺癌化学药物治疗 Copyri ght?Ameri can Soci et y of Cl i ni cal Oncol ogyOutcomes of Adjuvant Chemotherapy in Breast Cancer Walgren et al.JCO 2022;23:7342-7349 卫生部卫生部 医
