医学精品课件：1乳腺疾病.ppt

1、 Sir Run Run Shaw Hospital,Zhejiang University,Surgical OncologyLinbo WangSappys plexus lymphatics under areolar complex75%of lymphatics flow to axillaGross AnatomyBreast Blood vesselsMammary lymphMammary LymphLateral axillaryMedial parasternalboth sides the breast trafficDeep TRAM Sheath Falciform

2、ligament of liver lymph vessels and Lymph nodeAxillary lymph nodes of breastGroup I Armpit Group pectoralis minors laterales Group II central axillary group pectoralis minors deepGroup III upper axillary group pectoralis minors Breast Physiology Pituitary Thyroid Adrenal Ovarian Breast Examination V

3、isual inspectionContour(skin retraction,dimpling)Color(erythema).Texture(skin thickening or lymphedema)Skin retraction or dimpling.Nipple scaling or retraction.Nipple inversion(age of onset during adulthood).Location of abnormal findings or mass according to a clock face as the examiner faces the pa

4、tient,clearly indicating whether the abnormality is in the right or left breast.Size/extent of abnormal finding or mass.Breast Examination PalpationLocation in three dimensions(subcutaneous,midlevel,next to chest wall,Size and according to a clock face as the examiner faces the patient)Shape(round,o

5、blong,irregular,lobular having one to four rounded or curved extensions from a central mass).Mobility(mobile,fixed to skin or chest wall).Consistency(soft,similar to surrounding breast tissue,hard).External texture(smooth,irregular having bumps distributed over the external surface of the mass).Nipp

6、le discharge.(Spontaneous.Color.Number of involved ducts.Right or bleft breast,or both)normal breast The direction of abnormal nipple Flat nippleInverted nippleStellate scar skin contraction Dimple sign skin inward contraction Orange peel skinErythemaLump Mass Axillary lymph nodes protruding Ulcer N

7、ipple dischargePagets diseaseInflammatory breast cancerBreast CancerClinical Sympton:Painless mass Nipple Discharge Nipple eczema-like change Signs of cutaneous malignant The performance of other metastasisThe Diagnosis of Breast DiseasesHistoryPhysical examinationAdjuvant examinationPathologySpecia

8、l Adjuvant ExaminationMammographyUltrasoundMRI IR/LCD BenignProbably BenignProbably MalignantMalignantcystsolid mass(fibroadenoma)solid mass(cancer)Ultrasound Pathology Cytology:Fine needle biopsy Discharge Imprint Histology:Core needle biopsy U/S guided or sterotatic 90%effective in establishing di

9、agnosis Atypia need excision Incisional biopsy Excisional biopsyDifferential diagnosis of breast lumpsEndocrine:(cystic hyperplasia.)Tumor:(benign or malignant,epithelial/mesenchymal origin)Inflammatory:(acute/chronic,specific/non-specific)Traumatic:(fat necrosis/hematoma)Congenital:(multiple nipple

10、/multiple breast/hamartomaOther:(Tietze)Mastitis(acute)History Symptoms of red,swelling,heat,pain Treatment:prevention 1.Unobstructed drainage 2.Fomentation 3.Antibiotics 4.Abscess drainedAbscess drainedBreast Cystic hyperplasiaPain and and related with menstrual cycles Treatment:Chinese MedicineBre

11、ast Tumor1.Fibroadenoma20-25year-oldsinglelumpLargefibroadenomaTreatment:tumorresection/segmentresection Multiple FibroadenomaFibroadenoma 2.Intraductal papilloma Intraductal papillomatosis 3.Phyllodes tumor Treatment:Single breast excision Intraductal papillomaNipple linemultiple breast 4、Breast Ca

12、ncerRisk FactorsControllableAlcohol drinkingBeing overweightNever having children1st child 30yrs of ageHormone ReplacementBirth control pills(very slight)UncontrollableGetting olderFirst degree relative with breast cancerA previous breast biopsy showing atypical changesRisk FactorsControllableBeing

13、exposed to large amounts of radiationUncontrollableBeing young(7(+)unknown number rate number rate number rate number rate number rate （）（）（）（）（）T1 328 241 73.5 51 15.6 10 3.2 15 4.6 11 3.4T2 982 497 50.6 240 24.4 71 7.2 110 11.2 64 6.5T3 475 161 33.9 106 22.3 52 10.9 98 20.6 58 12.2T4 81 24 28.6 11

14、 14.3 10 13.1 16 20.2 20 23.8stage4 3 1 1 1unknown 320 217 67.8 39 12.2 14 4.4 22 6.9 28 8.8Total 2189 1140 52.1 448 20.5 158 7.5 262 11.9 181 8.3 Tang ZY Modern Oncology in September 2000 Histological type of breast cancer,lymph node metastasis and prognosis Type number rate lymph node survival（）To

15、tal survival (）metastasis rate 5Y 10Y 5Y 10YNon-invasiveCarcinoma 170 3.87 9.8 90-100 83.7-1/1 90.6 83.8Early stage invasive Carcinoma 91 2.07 23.3 77.7-88.2 77.7-88.2 92.3 78.0Invasive Special 500 11.37 43.5 50.8-100 39.1-100 77.0 62.8 Invasive No-special 3618 82.12 60.8 55.2-72.3 34.7-56.0 60.3 39

16、.5Other 17 0.39 53 47.1 22 47 22Total 4396 100 56.6 63.9 44.9 Tang ZY Modern Oncology in September 2000The overall effectiveness of cancer treatment1981-1994 year United States Caucasian the relationship between stage and the five-year survival rate in Common tumor Tumor tumor 5 years survival ratel

17、ocation regional 1981-1987 1983-1990 1986-1993 1986-1994 Localized 57 57 59 57 Stomach Regional 16 19 21 19 Distant 2 2 2 2 Localized 88 91 92 93 Colon Regional 58 61 64 67 Distant 6 7 8 9 Localized 41 47 49 51 Lung Regional 14 15 19 21 Distant 2 2 2 2 Localized 90 95 97 98 Breast Regional 50 75 77

18、78 Distant 14 19 21 23 Localized 89 95 100 100 Prostate Regional 80 87 95 100 Distant 29 30 31 3 2 Cancer Stastistics 1992-1999 years CA-Cancer J ClinTransfer ways:Lymphatic HematogenousSupraclavicular and cervical lymph nodesBreast cancer bone metastases(osteolytic destruction)Breast Cancer Staging

19、 T:Tumor N:Node M:MetastasisBreast Cancer TreatmentLocal treatment Surgery Radiotherapy OtherSystemic treatment Chemotherapy Endocrine therapy Immunotherapy Molecular Targeted therapy Traditional Chinese Medicine Treatment OtherDiagnosis of breast cancer:PathologycTNM+ERPR,Her-2Early stage(/)-Surger

20、ySystemic adjuvant therapy/radiotherapy(Chemotherapy/molecular targeted therapy/endocrine)Interim(/)-Neoadjuvant therapy SurgerySystemic adjuvant therapy/radiotherapy(Chemotherapy/molecular targeted therapy/endocrine)Late stage()-Systemic treatmentSurgery(radiotherapy)(Chemotherapy/molecular targete

21、d therapy/endocrine)ADJUVANT THERAPY FOR BREAST CANCER TREATMENT GUIDELINESGuidelinesNCCN=National Comprehensive Cancer NetworkNIH=National Institute of HealthSt.GallenNIHNCCN19781983 19881992 1995 1998 2001 2003200519801985199020001996yearly中国抗癌协会乳腺癌专业委员会中国抗癌协会乳腺癌专业委员会2007乳腺癌诊治指南乳腺癌诊治指南/规范规范CBCS第五届

22、委员名单2006-12-31CBCS主主 任委员：任委员：邵志敏（复旦大学肿瘤医院）副主任委员：副主任委员：宋三泰（军事医学科学院解放军三七医院）,方志沂（天津医科大学肿瘤医院）,张斌（辽宁省肿瘤医院）常委：常委：王永胜（山东省肿瘤医院）宁连胜（天津医科大学肿瘤医院）任国胜（重庆医科大学第一医院）张保宁（中国医学科学院肿瘤医院）张瑾（天津医科大学肿瘤医院）杨名添（中山大学肿瘤医院）沈坤炜（复旦大学肿瘤医院）吴凯南（重庆医科大学第一医院）欧阳涛（北京大学肿瘤医院）顾林（天津医科大学肿瘤医院）原俊（湖北省肿瘤医院）吴炅（复旦大学肿瘤医院）秘书：秘书：吴炅（复旦大学肿瘤医院）委员：委员：乔新民、李金

23、峰、王天峰、徐晓娜、江泽飞、王东民、骆成玉、孙强（北京）；陆劲松、李亚芬、陈佳艺、杨文涛、顾雅佳、胡夕春（上海）；只向成、刘红、佟伸生、刘佩芳、付丽、冯玉梅（天津）；姜军（重庆）；张清媛、庞达（黑龙江）；王长青、刘克（吉林）；范忠林、刘巍、张培礼（河北）；刘奇伦（宁夏）；赵庆丽（甘肃）；陈武科（陕西）；左文述（山东）；霍树德、冯爱强、谷元廷（河南）；朱继荣、武正炎、唐金海（江苏）；吴金民、张苏展、王林波、黄建、张筱骅（浙江）；张红雁、刘爱国（安徽）；孙圣荣（湖北）；罗以、席许平、周征宇（湖南）；于震、马行天、雷秋模（江西）；陈夏、许林、许建华、陈晓耕、林舜国（福建）；吕肖（四川）；汤学良（云南

24、）；陆云飞（广西）；潘志忠、苏逢锡、王颀（广东）；汤鹏（海南）；马斌林（新疆）；毛大华（贵州）Breast cancer does not require adjuvant treatment(NCCN Breast Cancer Practice Guidelines 2007.2 Version)Axillary lymph node-negativeTumor(T)Situ Micro-invasive carcinoma T 0.5cm Tubular carcinoma,mucinous adenocarcinoma,T 1.0cm Other types ,0.6-1.0 cm,n

25、o adverse factorsUnfavorable factors:Vascular invasion,large nuclear atypia,poor tissue differentiation and HER-2 overexpression,ER(-)St.Gallen 2005 Risk CategoryLowIntermediateHighG1T2 AGE2Node+(3)And HER2+Node+4Node-,HER2+or LVI present Node+(13)and Her2-Node-HER2-LVI absentRISKRISK Risk Category

26、1 End.Resp.2 End.Resp.Uncertain2,3 End.Non Resp.2 Low Risk Average Risk HER2+Higher Risk HER2+ET ETET alone orCT ET(CT+ET)TrastuzumabCT ET(CT+ET)TrastuzumabNA2CTTrastuzumabCT ET(CT+ET)TrastuzumabCT TrastuzumabCT ET(CT+ET)TrastuzumabThe basic principles of adjuvant therapySt Gallen 2009：乳腺癌综合治疗选择方法方法

27、指征指征说明说明内分泌治疗内分泌治疗任何程度ER表达ER-而PR+可能是检测误差引起分子靶向治疗分子靶向治疗IHC或FISH验证HER-2阳性临床试验标准亦可供参考化疗化疗 HER-2阳性病例阳性病例（联用靶向治疗）（联用靶向治疗）曲妥珠单抗只有联用或续贯化疗使用的证据内分泌治疗+靶向治疗（ER&HER-2+），而不用化疗逻辑上可行但没有循证学依据 三阴乳腺癌三阴乳腺癌绝大多数患者大多数风险较大，暂无其他可选治疗 ER+,HER-2-病例病例（联用内分泌治疗）（联用内分泌治疗）根据各风险因素决定根据各风险因素决定?!见下图G1G1T1 T1 PVIPVILNLN阴性阴性低增殖水平低增殖水平高高

28、ERER、PgRPgR水平水平多基因分析低分多基因分析低分患者意愿避免化疗患者意愿避免化疗G3G3T3T3以上以上PVI+PVI+LN+LN+（44）高增殖水平高增殖水平低低ERER、PgRPgR水平水平多基因分析高分组多基因分析高分组患者有意愿接受化疗患者有意愿接受化疗G2G2T2T2LN+LN+（1-31-3）中等增殖水平中等增殖水平多基因分析中间组多基因分析中间组倾向单独内分泌治疗倾向单独内分泌治疗倾向内分泌治疗倾向内分泌治疗+化疗化疗无用信息？St Gallen 2009：ER+,HER-2-乳腺癌化疗决策因素？Goldhirsch A,et al.Ann Oncol Epub 200

29、9 JunPVI,peritumoral vascular invasion 瘤旁血管浸润瘤旁血管浸润 William Stewart HalstedBreast cancer treatment乳腺癌外科发展历程“Radical”Meyer.1891 Halsted.1894“Extended”Margottini.1949 Urban.1951“Modified”Patey.1949 Auchincloss.1951“Conservative”Veronesi.1973 Atkin&Hayward.1977“Sentinel node biopsy”DavidKrag.1992 The s

30、urvival rates of I/II phase of breast cancer modified radical mastectomy Comparied with breast-conserving surgerySimple mastectomy+Axillary lymph node dissectionBreast-conserving surgery+RadiotherapyLocal recurrence rate5 years survival rate 29%420%No statistically significant differenceThe worlds s

31、ix prospective randomized clinical trial results The Impact of Postoperative Radiotherapy on survival RateInternational Early Breast Cancer Collaborative Group36 group of randomized trials in patients with a total of 29175 casesNo chemotherapy or endocrine therapyRadiotherapy No Radiotherapy P value

32、Total survival rate 40.3%49.4%0.3 Conclusion:Radiotherapy did not significantly improve survival,it can reduce the rate of postoperative local recurrence 术后放疗对生存率的影响术后放疗对生存率的影响放疗组放疗组未放疗组未放疗组P值值总生存率总生存率40.3%49.4%0.3未用化疗或内分泌治疗时代的结果：未用化疗或内分泌治疗时代的结果：国际早期乳癌试验协作组 36组随机试验共29,175例患者v结论：结论：未明显提高生存率Radiothera

33、py vs.NotISOLATED LOCAL RECURRENCES91.5%72.9%18.7%(se0.6)91.5%90.4%70.4%19.9%(se0.7)Actuatial estimate and SE:-allocated RADIO.-allocated CONTROLProportional reduction in local recurrence is of similar size(about 2/3)in all major studies,old or new.1008060402002001020yearEBCTCG 关于乳腺癌术后放疗的结论关于乳腺癌术后放疗

34、的结论（2000年9月 20000例）v局局 部部 复复 发发 率：率：04 年，降低2/3v乳腺乳腺 癌癌 死亡死亡 率：率：515年，降低1/6v非乳腺癌死亡率：非乳腺癌死亡率：15年后，增加1/3术后放疗适应症：术后放疗适应症：2006前前v1-3个淋巴结阳性但腋窝清扫不彻底个淋巴结阳性但腋窝清扫不彻底vT3或或4个淋巴结阳性个淋巴结阳性v1-3个淋巴结阳性、腋窝彻底清扫者还需进一步评价个淋巴结阳性、腋窝彻底清扫者还需进一步评价 (推荐选择放疗推荐选择放疗)EBCTCG.Breast-conserving SurgeryEBCTCG.Breast-conserving SurgeryEB

35、CTCG.MastectomyEBCTCG.MastectomyEBCTCG Overview Lancet 2005,366:2088-2106全乳放疗全乳放疗保乳术后放疗近70的5年复发风险 17的15年死亡风险0%0%1%1%2%2%3%3%4%4%5%5%6%6%NSABP B-06NSABP B-06Milan-3Milan-3Ontario COGOntario COGNSABP B-21NSABP B-21Swedish BCCGSwedish BCCGScottishScottishWest Midlands,UKWest Midlands,UK肿块切除肿块切除肿块切除+放疗肿

36、块切除+放疗复发事件复发事件/人年人年EBCTCG.Lancet,2005.Radiation therapy and Surgical treatment -local treatment mutual complementSurgical dissection insufficientLarge mass 5cm,Axillary lymph node metastasis 3,(1-3)Post-operation of Breast-conserving surgerylocal recurrence Distant metastasisBreast cancer is the sys

37、temic disease-Effective systemic treatment is the key pointEffective chemotherapy can increase the survival rate of breast cancer-side effect 100%Neo-adjuvant chemotherapy-First-line programAdjuvant chemotherapy-First-line programTreatment of chemotherapy(later period)-First-line/second line program

38、Rescue chemotherapy(Patients with recurrence and metastasis)-First-line/second line/Third line programCommon Program:CMF,FAC,AC,FEC,EC,TAC,TEC.Endocrine therapy can increase the survival rate of breast cancer-Less side effect compared with chemotherapy Postmenopausal patient:Endocrine therapy chemot

39、herapy According to ER,PR(+)/(-)Neo-adjuvant endocrine therapyAdjuvant Endocrine therapyTreatment of endocrine therapy(later period)Rescue endocrine therapySelective estrogen receptor modulator:TAM,TOR Aromatase inhibitorsCastration:Drug,surgery,radiation辅助化疗和内分泌治疗231740173213卵巢去势对卵巢去势对ERER5 5年年TAMT

40、AM对对ERER联合化疗联合化疗10050危险度危险度复发危险度复发危险度死亡危险度死亡危险度EBCTCG,Lancet,2005Bio-targeted therapyHerceptin-HER2+Metastatic Breast CancerImmunization agents-AdjuvantTraditional Chinese Medicine-There is no credible evidence 适应证Her-2/neu基因过表达免疫组化法(IHC)3+，或荧光原位杂交法（FISH）阳性，或者色素原位杂交法（CISH）阳性Her-2 IHC2+的患者值得进一步FISH或C

41、ISH明确Vogel CL,et al.J Clin Oncol 2002;20:71926紫杉类化疗联合赫赛汀NCCTG N9831和NSABP B-31联合分析 DFSRomond et al 2005Years from randomisation87%85%67%75%HR=0.48;p0.000110090807060500123452-year median follow-up Pts(%)AC PAC PHnEventsACPH1672133ACP1679261近年来乳腺癌辅助治疗取得的进展近年来乳腺癌辅助治疗取得的进展疾病相关复发风险降低百分比疾病相关复发风险降低百分比17%4

42、2%46%31%CEF vs CMFLevine 2005AC T vs ACHenderson 2003Piccart 2005三苯氧胺三苯氧胺 vs 安慰剂安慰剂Fisher 2004DAC vs FACMartin 200528%HER2+HER2+&HER2-HER2-Romond 20050102030405052%HER2+HER2+化疗化疗 +赫赛汀赫赛汀 vsvs 化疗化疗化疗化疗 赫赛汀赫赛汀 vsvs 化疗化疗2005 2005 ASCOASCO乳腺癌的部分新进展前哨淋巴结问题前哨淋巴结问题!The ALMANAC Trial(U.K.)The Axillary Lymph

43、atic Mapping Against Nodal Axillary Clearance(ALMANAC)trial.NSABP B-32Randomized Multicenter Trial of Sentinel Node Biopsy Versus Standard Axillary Treatment in Operable Breast CancerThe ALMANAC TrialFrom November 1999 to October 2003,1031 patients were randomly assigned to undergo sentinellymph nod

44、e biopsy(n=515)or standard axillary surgery(n=516).Patients with sentinel lymph node metastases proceededto delayed axillary clearance or received axillaryradiotherapy(depending on the protocol at the treating institution).Intention-to-treat analyses of data at 1,3,6,and 12months after surgery are p

45、resented.Sentinel Node BiopsyA radiopharmaceutical compound A blue dye Outcome Assessments Arm morbidity：Lymphedema；Shoulder function；Sensory deficits Infection rate Quality of life：FACT-B+4The ALMANAC TrialArm morbidityArm morbidityArm morbidity assessmentpLymphedemaSelf-assessment Moderate or seve

46、re.001Mean change in arm volume.005Sensory deficit Self-assessment.1Clinician assessment of ICB nerve damage.001Mean change in shoulder function Flexion.004 Abduction.001Other effect endpointQuality of lifeQuality-of-life scoresBaseline1mo3mo6mo12moTrial outcome index,mean(95%CI)Sentinel lymph node

47、biopsy86.782.984.484.989.2 Standard axillary treatment87.778.781.982.487.1p vs 2 cm)Age(50 years and older vs younger than 50 years)NSABP B-32:Local and Regional Recurrence Rates Similar in Both Groups00.51.01.52.02.53.0LocalAxillaryExtra-axillaryPatients(%)Recurrence Type2.72.40.10.30.250.3SNR+ALND

48、(n=1975)SNR(n=2011)NSABP B-32:Significantly Lower Morbidity Without vs With ALND051015253035Patients(%)SNR+ALND(n=1975)SNR(n=2011)Shoulder Abduction Deficit 1913Arm Volume Difference 5%2817137Arm TinglingArm Numbness31820P .001P .001P .001P .001NSABP B-32:ConclusionsIn clinically node-negative patie

49、nts,ALND following SNR did not improve survival or regional control vs SNR aloneNo significant differences in OS,DFS,or locoregional recurrenceTheLancetOncology,21September2010,KragDNNSABP B-32:ConclusionsSNR without ALND associated with significantly lower morbidity and higher postoperative quality

50、 of lifeSNR alone without ALND appears safe and effective therapy for clinically node-negative breast cancer patients when SNR also negativeTheLancetOncology,21September2010,KragDN 区域淋巴引流示意图区域淋巴引流示意图常规术前造影并不必要常规术前造影并不必要内乳区内乳区SLNBSLNB方法可行方法可行术前造影可选择应用术前造影可选择应用1.SLN送冰冻切片送冰冻切片2.局部扩大切除标本送切缘局部扩大切除标本送切缘SL