治療乳癌的診斷 分期及治療準則 照護乳癌的照護目標 照護標準或癌症核心測量指標

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1 台灣護理學會 腫瘤個案管理護理師培訓課程乳癌 Ming-Feng Hou, M.D. Department of Surgery Kaohsiung Medical University 侯明鋒第三屆乳房醫學會理事長高雄醫學大學外科教授癌症中心主任 腫瘤個案管理護理師培訓課程乳癌 治療乳癌的診斷 分期及治療準則 照護乳癌的照護目標 照護標準或癌症核心測量指標 2010 年 8 月 22 日 ( 星期日 ) 上午 9:20~10:10 上課地點 : 國立台灣大學醫學院基礎醫學大樓 502 講堂 ( 台北市仁愛路一段 1 號 ) 上課主題 : 乳癌的診斷 分期及治療準則癌症診療準則與核心測量 乳癌的診斷 分期及治療準則 Breast Cancer Diagnosis, Staging & Therapy Epidemiology 流行病學 & Diagnosis 診斷 Staging 乳癌之分期 Treatment 治療準則 Surgery 外科手術 Radiotherapy 放射線治療 Adjuvant Therapy 輔助性治療 1. Chemotherapy 化學治療 2. Expression analysis 基因表現 3. Endocrine therapy 內分泌治療 4. Tailored therapy 剪裁治療 5. Patient involvement 病患參與 Contents A. Anatomy and physiology B. Clinical Examination and Diagnostic Methods C. Benign disease D. Malignant disease a. Epidemiology and Risk Factors b. Symptoms of Breast Cancer c. Treatment 1. Surgery 2. Adjuvant Therapy 3. Radiation Epidemiology 流行病學 & Diagnosis 診斷 A. Anatomy and Physiology (1) A. Anatomy and Physiology (2) Anatomic Distribution of Breast Lymphatic Drainage I II III SLN Axillary 75 % a. Lateral b. Anterior (pectoral) c. Posterior (subscapular) d. Central e. Apical Int. mammary 25 % Level I Nodes lateral to pectoralis minor Level II Nodes pectoralis minor Level III Nodes medial to pectoralis minor

2 A. Anatomy and Physiology (3) Microscopic Anatomy B. Clinical Examination and Diagnostic Methods Galactography 1. Lactiferous sinus 2. Extralobular terminal ductule 3. Intralobular terminal ductule 4. Terminal ductule 5. Lobule Physical examination (PE) Breast self - examination (BSE) Diagnostic tools Mammography Sonography Needle biopsy Mammotone Thermography MRI, C-T Digital Imaging system B. Clinical Examination and Diagnostic Methods a.physical examination (PE) Sitting position Supine position Inspection Palpation Skin Erythema Patch Symptoms in inspection Skin Retracted (Cancer) Inflammatory Breast Ca Nipple Fibroma Male Monder s Disease Vertical Strip Method Wedge Method Circular Method Differential Pressure Nipple retracted ca Inverted nipple Ulcerated ca Bulging Skin in Inframammary Fold Regional Lymph node Position Change in Large Breast or Outer Quadrant Skin Eczema Paget s s Disease LABC Palpation Symptoms of breast disease B. Clinical Examination and Diagnostic Methods b. Breast self - examination (BSE) Mass located Axillary Area (Lipoma) Cancer Sarcoma Male Breast Cancer Aged 20 years (American Cancer Society) day after menstruation, per month (breast nodularility, tenderness less). Post menopausal the same day each month. Lactating mother empty their breast. Bloody Serous Milky Sarcoma Symptom percentage Painless mass 82 Painful mass 6 Nipple discharge 7 Skin retraction 2 Others women; Shang-Hei; China Study:133375; Control: Age:31-65 years old Breast Cancer: 331 : 322 Similar Stage, Size BSE: More benign tumor (1453;623) F/U 5 yrs; similar death rate J Natl Cancer Inst Oct 2;94(19): (Fred Huntchninoson and Shang-Hei center)

3 B. Clinical Examination and Diagnostic Methods Performance characteristics of screening modalities Modality Total Abnormal screens c. Diagnostic tools Biopsy cases Cancer detected Sensitivity Specificity CBE (1.8%) 12(1.2%) 7(0.7%) 33.3% 83.5% Mamm (6.0%) 15(1.6%) 11(1.1%) 52.4% 82.2% Sono (12.9%) 24(2.5%) 19(2.0%) 90.4% 86.3% Diagnostic tools Mammography Indication Suspicious lesion Dominant nodule Follow-up (BCS, Contralateral breast) Screen Large fat breast Composition Almost Entirely Fat Replacement Scattered Fibroglandular CBE-clinical breast examination; Mamm-mammography; Sono-sonography (Hou MF.et al. Ultrasound in Medicine and Biology 4,2002;28: ) CC View Cranial Caudal MLO View Medial Lateral Oblique Heterogeneously Dense Breast Extremely Dense Breast American College of Radiology (ACR) Breast Imaging Reporting and Data System (BI-RADS) Mammographic Findings (I) Masses: Shape, Margin, Density Lexicon of terminology to standardize Calcifications: language, reporting structure and Typically benign Intermediate concern decision-oriented approach Higher probability of malignancy Distribution: clustered, linear, segmental, regional, scattered Mass Typically benign Round cal. Lucent-centered cal. Milk of calcium cal. Rim cal. Coarse cal. Vascular cal. Skin cal. Solid-rod cal. Suture cal. Dystrophic cal. Intermediate concern amorphous Higher probability of malignancy granular branching Mammographic Findings (li) Calcifications Types 1. Round 2. Lucent-centered 3. Milk of calcium 4. Acinar 5. Rim 6. Coarse 7. Coarse 8. Vascular 9. Skin 10. Solid rod 11. Granular 12. Branching Cluster Linear Segmental Regional Scattered Mass Shape Mass Margin Round Oval Irregular Cysts Lucentcentered Scatter Calcification cal Regional Linear Coarse Suture DCIS calcification Fat Granuloma necrosis Cluster DCIS Coarse cluster Porcorn CaVascular Cal Mammographic Findings (IIl) Associated findings Skin retraction Nipple retraction Skin thickening Trabecular thickening Skin lesion Axillary adenopathy Architectural distortion Lesion Location Final Assessment Categories For Mammography 0. Need additional imaging evaluation 1. Negative 2. Benign finding - negative 3. Probably benign- short interval follow-up suggested 4. Suspicious abnormality- biopsy should be considered 5. Highly suggestive of malignancy- appropriate action should be taken 6. Known cancer

4 B. Clinical Examination and Diagnostic Methods c. Diagnostic tools Indication of Breast Ultrasound Targeted breast Multiple lesions Reconstructed breast, Silicon leak Family history Breast secretion Screening? Dense breast Young breast Pregnancy Cyst, abscess Assist mammography Non-palpable mass Echo-guiding Diagnostic Pictures for Breast Ultrasound Ultrasound Evaluation of Focal Breast Lesions Shape: round, oval, pleomorphic Contours: smooth, irregular Margins: Sharp, ill-defined Internal structure: Homogeneous, heterogeneous Echogenicity: Anechoic, hypo, hyper Sound transmission: Enhanced, unchanged, attenuated Edge shadows: none, unilateral bilateral Size: Three dimensions Axial orientation: Horizontal, vertical, indifferent Compressibility: Compressible, noncompressible Mobility: Very, slightly,immobile Individual Sonographic Characteristics Benign Echo Pattern Malignant Benign Indeterminate Simple cyst Simple cyst Complex cyst Abscess Spiculation Absent malignant findings Maximum diameter Angular margins Intense hyperechogenicity Isoechogenicity Marked hypoechogenicity Ellipsoid shape Mild hypoechogenicity Shadowing Gentle bi- or trilobulations Normal sound trasnsmission Calcification Thin, echogenic pseudocapsule Enhanced transmission Duct extension Heterogeneous texture Branch pattern Homogeneous texture Microlobulation Lactational cyst Lipoma FC (Stavros et. el.radiology;1995:196: ) Fb Pappill omatosis Malignant Echo Pattern BIRAS Ultrasound (Modified American College of radiology Breast Imaging Reporting and Data System) Categories Description Risk of Management Malignancy (%) Ca IDC CA Normal 0 Clinical lump F/U; screening 2 Benign finding 0 Clinical lump F/U; screening 3 Probably benign 2 F/U or biopsy Ca Papillary Ca 0.8x0.7x0.4 cm DCIS microcalcification 4a Mildly suspicious >2 and <50 Biopsy (additional image) 4b Moderately >50 and <90 Biopsy suspicious 5 Malignant 90 Biopsy 6 Known Malignant 100 proved

5 每十萬人口年齡 標準化發生率 年度 ( 年 ) 台灣女性乳癌年齡標準化發生率之長期趨勢, 依性別分, 年 Indications of Breast MRI Conventional imaging: radiographically dense breast, silicone augmented breast, postop scar Pre-Op. staging for conservative surgery Determination of the source of LAP Monitoring the efficacy of C/T High Risk Group Elmore JG et al Screening for breast cancer. JAMA Mar 9;293(10): Review. 美國黃伯榮醫師提供 Values of Ultrasound,Mammography and MRI in Different Diagnostic Settings Ultrasound Mammography MRI Pregnancy Peripheral lesions + + to - + Bedridden patients Cystic lesions Abscess Prosthesis Dense breast + + to - + Involuted breast + to Microcalcification + to Intraductal masses + to - + (Ductography) + Surgical specimen + to Screen? + + Interventional + + to - +to - Cost Cheap Moderate High Congenital abnormality C. Benign Breast Disease Breast cysts C.Benign Breast Disease Common 7 % population 20 % subclinical Unknown --estrogen 45 ~ 52 y/o 5 c.c ~80 C.c Sono., mamm. Aspiration, Biopsy Accessory Nipple Abscess and Mammary fistula Fibroadenoma Accesory Breast Asymmetric Aspiration + Antibiotics Drainage Excision (recurrent) -- Lobule, unknown etio. -- Young age 16~24 y/o -- 2~3 cm % multiple -- Oriental, Black -- Aspiration cytology --<35 y/o conservative -- Recurrent Cyclical nodularity Lipoma adenolipoma Size with menstrual cycle Discomfort, mastalgia Upper outer quadrant Conservative treatment or Biopsy suspicious Excision Variation Hamartoma Phyllodes tumor -- Phyllodes sarcoma, cystosarcoma, cystosarcoma phyllodes -- Locally, aggressive, meta. -- Hypercellularity, atypia, mitoses -- 30~50 y/o -- Wide excision (>1 cm) % recurrent a. Epidemiology and Risk Factors D. Malignant Diseases 乳癌年齡標準化率之長期趨勢, 年 男女性十大癌症發生分率, 2003 年 年齡標準化率 ( 每十萬人口 ) 發生率死亡率 發生年代 D. Malignant Diseases 2006 年女性乳房年齡別發生率與死亡率 a. Epidemiology and Risk Factors (6,753 人 ) 肝 19% (5,025 人 ) 肺 14% (4,677 人 ) 結腸及直腸 13% (4,040 人 ) 口腔 11% (2,308 人 ) 胃 6% (2,237 人 ) 攝護腺 6% (1,318 人 ) 膀胱 4% (1,258 人 ) 食道 3% (1,157 人 ) 鼻咽 3% (960 人 ) 皮膚 3% (6,552 人 ) 其他癌症 18% 男性共 36,285 人備註 : 子宮頸癌含原位癌, 口腔癌含下咽及口咽 20% 乳房 (5,325 人 ) 14% 結腸及直腸 (3,561 人 ) 民國 年乳房原位癌與侵襲癌發生個案數圖發生數 10% 肝 (2,651 人 ) 6,000 原位癌 5,325 9% 肺 (2,390 人 ) 侵襲癌 4,879 5,000 4,784 4,619 8% 子宮頸 (2,061 人 ) 4,437 5% 胃 (1,226 人 ) 4,000 3,764 3,575 3,052 4% 甲狀腺 (975 人 ) 3,000 2,792 2,368 2,464 3% 卵巢 (833 人 ) 2,238 2,000 3% 子宮體 (793 人 ) 1,000 3% 皮膚 (783 人 ) % 其他癌症 (5,659 人 ) 0 民國年 女性共 26,257 人 2006-Dec-19 DCIS:506 人 男性 女性 年台灣女性乳癌年齡發生率之長期趨勢

6 a. Epidemiology and Risk Factors Risk Factors Early menarche Late menopause Nulliparty HRT Alcohol Postmenopausal weight gain Irradiation Atomic bomb survival Late age of first pregnancy Human Genetics. 104(3):201-4, 4, 1999 Associated genes in Hereditary Breast Cancer BRCA1 BRCA2 P53 ATM PTEN Pedigree of Wei ( 魏 ) Br:Breast Cancer Cx:Cervical Cancer Col:Colon Cancer Ov:Ovary Cancer :BRCA1 mutation 40 Col 30Br Ov Cx 54 Col 50 Br Ov Ov The Relationship of Benign to Malignant Disease No risk Sclerosing adenosis Apocrine change Duct ectasia Fibroadenoma Cyst Mild hyperplasia Apocrine metaplasia Risk (1.5-2x) Moderate hyperplasia Papilloma Risk (4-5x) ADH (Atypical Ductal Hyperplasia) ALH (Atypical Lobular Hyperplasia) Risk (8-10x) DCIS (Ductal Carcinoma In Situ) LCIS (Lobular Carcinoma In Situ) b. Symptoms of Breast Cancer 乳癌之分期 AJC C 7th edition Clinical stage Pathological stage Postneoadjuvant therapy clinical or imaging (yct) or pathologic findings (ypt) 乳癌之分期 Paget s Dis Skin Retracted Orange Skin Nipple Retracted Nipple inverted Mass Biopsy Scar Mass Bloody Discharge LABC Blood clot LABC Claudiflower Mass Ulcerated LABC 行政院衛生署國民健康局 2008 年 10 月 17 日公佈 BREAST CANCER Survival by Stage Stage 0&I : 55% vs 37% Percent surviving Stage 0 Stage I Stage IIA Stage IIB Stage IIIA Stage IIIB OS 5yr% I II III IV Taiwan Total OS: 89% vs 83% US 資料來源 : 台灣 : 癌症登記 ( 診斷年為 2002 年, 計有 10 家醫院申報 2,174 個案, 完整追蹤 5 年資料 ) 美國 : 美國癌症委員會癌症資料庫. Survival Report, 2008( 診斷年為 年共 299,900 個案, 完整追蹤 5 年資料 ) Years after diagnosis Stage IV

7 c. Treatment for Breast Cancer Diagnosis Surgery 外科手術 Treatment Molecular Diagnosis Cytology Core biopsy Open biopsy Local excision Axillary Dissection (Sentinel Node) Mastectomy Aspiration Cytology Easy method Insufficient sample Liu s Stain Core biopsy 14G 5 samples 16G Preop Diagnosis Open biopsy Definite diagnosis Cost Directional Vacuum-Assisted Breast Biopsy Benign Lesion after Mammotone Biospy Large core, single pass biopsy device Guided either stereotactically or by ultrasound Directional by virtue of side aperture High accuracy due to good quality biopsy cores Related to vaccuum-suction Allows marker clip placement Low complication rate Obtain larger volume of sample Decrease histologic underestimation Decrease rebiopsy (Mammotome) Pre biopsy 7days after MMT Mammotome 3months after MMT Post biopsy Needle Localization for Nonpalpable Lesion Microcalcification DCIS Comparison of Image-Guided Biopsies Methods Methods mg / sample FN / FP Needle localization Failure % (mean 2.6%) FNAC Insufficient sampling 35.4% 0-7.9% (mean 2%) 11.5% / 8.6% Underestimation ADH DCIS 14G Automatic Core 17 mg 0-8.2% % % 14G Vacuum 35 mg 0-39 % 0-17 % 11G Vacuum 100 mg % 4-15 % <3cm: 3% Single pass Advantages >3cm: 43% Larger, higher quality core Core biopsy 14G MMT biopsy 14G 17-18mg 34-40mg FN: False Negative Rate FP: False Positive Rate MMT biopsy 11G 94-96mg Lowers rate of underdiagnosis (ADH vs DCIS) understaging (DCIS vs IDC) 0% upgrading in 281 lesions (6 ADH; 30 DCIS; 15 IDC) Potential for complete excision (Heywang-Kobrunner. Eur Radiol 1998)

8 乳癌外科治療之發展 THE EVOLVING LANSCAPE OF BREAST CANCER SURGICAL THERAPY c.treatment 1.Surgery Rembradant (Bathsheba) Willian Stewart Halsted( ) 1922) Radical en bloc surgery Ann Surg 1907;46:1 D. H. Patey( ) 1977) MRM Umberto Veronesi Bernard Fisher NSABP(1918-) NEJM.1993;328:1581 systemic hypothesis Hellman S Spectrum Theory JCO 1995; 13: 8-10 Heterogeneous 1894~ Modified Radical Mastectomy 乳房切除手術 Sentinel node biopsy Imaged-Guided Ablation? Extended Radical Reconstruction Mastectomy Oncoplastic surgery 乳房保留手術 Lumpectomy 標靶生物製劑口服化療藥物 Oral chemotherapy Targeted biologics 劑量緻密化療藥物 Antiangiogenic Chemotherapy 抗荷爾蒙製劑 biologics 注射化療藥物 Anti-hormone therapy 抗血管新生生物製劑 ; 1933; 250 cases Middlesex Hospital Br Med J 1962, 2:213 Anatomic Structures Removed in Various Operations Extended Radical Mastectomy Skin Gland Areola Pector alis major Quardrectomy Pecto ralis minor Level I LevelI I Level III Interna l Node Supracl avicular Node Breast Conserving Surgery (BCS) Simple mastectomy MRM (Auchincloss) MRM (Patey) RM Super RM The dissection of internal mammary nodes does not improve the survival of breast cancer patients. 30-year results of a randomised trial.(737 patients) MRM (Modified Radical Mastectomy VS Radical Mastectomy) MRM MRM vs RM RM 558 patients who died in the 30 year interval period, 395 (71%) died from breast carcinoma (201 in the Halsted group and 194 in the extended mastectomy group) and 163 from other causes Eur J Cancer Sep;35(9): Veronesi U, et al. Donegon WL. Cancer of the Breast, Staging and Primary Treatment p413,1995 (Turner L, Ann R Coll Surg Engl. 1981;63: ) Wilson, R. E.The 1982 national survey of carcinoma of the breast in the United States by the American College of Surgeons. Surg Gynecol Obstet 159: Manchester trial Types No OS% DFS% Radical % 75% MRM % 79%

9 NSABP B women with clinically negative node 586 women with clinically positive node 1st Trial BCS 1961 Guy s Hospital, London Hedley Atkins The Guy's trial of treatments of "early" breast cancer. Hayward JL. World J Surg May;1(3): Discourage Higher local Recurrence Worse survival Low dose radiation Comparison of radical mastectomy with alternative treatments for primary breast cancer. A first report of results from a prospective randomized clinical trial.fisher B, Cancer Jun;39: Findings from NSABP Protocol No. B-04: comparison of radical mastectomy N Engl J Med, 347:567-,2002 with alternative treatments. II. The clinical and biologic significance of medialcentral breast cancers.fisher B, Cancer Oct 15;48(8): Five-year results of a randomized clinical trial comparing total mastectomy and segmental mastectomy with or without radiation in the treatment of breast cancer.fisher B, N Engl J Med. 1985, 14;312(11): Long-term follow-up of the first breast conservation trial: Guy' wide excision study. Fentiman IS. Breast Feb;9(1):5-8. National Surgical Adjuvant Breast and Bowel Project Protocol were treated by LO and 517 were in the LXRT group Twenty-year follow-up of a randomized study comparing breast-conserving surgery with radical mastectomy for early breast cancer Cancer 2001;91: N Engl J Med, 347, 1233-, women, T <2 cm RM ( 349 patients) BCS + RT ( 352 patients) (Veronesi U, NEJM 347: ) NIH consensus conference. Treatment of early-stage breast cancer JAMA. 1991;265: Breast conservation with or without radiotherapy Trials No WE F/U Local recurrence(%) Survival(%) (yrs) BCS BCS + RT BCS BCS + RT B Lump ± RT Swedish 381 Qurd ± RT Ontario 799 Lump ± RT Milan 567 Qurd ± No difference RT Scottish 585 WE ± RT Similar West Midlands 707 WE ± RT CRC 535 OP±RT No difference N Engl J Med 2002;347: Anatomic Distribution of Breast Lymphatic Drainage I II III Axillary Metastasis with T1a Primary Winchester, SSO, % SEER ( ) JNCI, % SEER ( ) JNCI, % Cady, Arch Surg, % McGee, Am J Surg, % Staging Therapy SLN

10 Morbidity of Axillary LN Dissection Infection SLN Axillary Drain Mayo Clinic 6% 34% Seroma Chicago 2.6% 27% Lymphedema Northwestern 3% 17% Post mastectomy pain syndrome Limitation of Shoulder Motion Paresthesia Indications for Sentinel Lymph Node Dissection Patient-related factors Age, Body mass Tumor-related factors Histology Ductal (84.5%) >Lobular, Early Ca Type of operative Procedure Biopsy(-), BCS, Mastectomy, SSM, Blanchard DK. Arch Surg 2003;138 :482 Martin GM. Am Surg 2003;69:209 Haid A.Breast Cancer Res Treat 2002;73:31 Controversial Previous axillary surgery Multicentric disease Suspicious axillary lymph nodes Neoadjuvant chemotherapy DCIS? Prophylactic mastectomy Contraindication Pregnancy Lactation Clinical N2 Inflammatory Procedures of SLN identification Isotope method 90-99% Dye method 80-95% Combined methods % Blue dye Stained SLN Stained SLN Preop Probe Intraop Probe Intraop SLN Isotope Neoprobe preop Incision wound Intraop SLN Probe detect SLN Preoperative Lymphoscintigram ILQ tumor with axillary SLN SLN Int. mammary chain and axillary LNs SLN SLN Supraclavicular LN Clavicle SLN T T IM T T Supraclavicular LN and axillary LNs IM:Internal mammary chain T: tumor SLN: Sentinel lymph nodes Lymphoscintigram SLN ID rate FN Rate Mean # SLN Yes 310/348 (89.1%) 8.7% 2.00 No 221/240 (92.1%) 1.6% 2.16 Total 531/588 (90.3%) 6.1% 2.07 No significant differences Amer J Surg 2004;188:49-61 A Randomized Comparison of Sentinel-Node Biopsy with Routine Axillary Dissection in Breast Cancer (AXD:257; SN:259; T<2cm) Umberto Veronesi, N Engl J Med 2003;349: Positive Cytokeratin Staining Shows Micrometastasis In SLN m-rna (Mammoglobin) CEA, CK-19, CK-20, MUC-1, GA733, etc (Bostik, JCO, Aug, 1998) RT-PCR Markers Consensus Statement on Guidelines for Performance of Sentinel Lymphadenectomy for Breast Cancer Contraindications: Suspicious palpable axillary lymph nodes Prior breast radiation therapy Extensive prior breast surgery or axillary surgery Invasive multifocal disease Pre-operative chemotherapy Indications SLN should be considered for patients with DCIS who are undergoing mastectomy. It is highly recommended that all patients who are candidates for SL have this procedure discussed as an option in their surgical management. 20 cases,combination methods (The American Society of Breast Surgeon 2006)

11 Nipple Discharge 乳頭流血 Is a step operation for breast cancer patients presenting nipple discharge without palpable mass feasible? Prolene suture Histologies Galactography Intraductal cytology Both Ca 32/35 (91.4%) 34/35 (88.6%) 34/35 (97.1%) Benign 109/141 (77.3%) 119/141(98.4%) 127/141 (90.0%) OP methods No Recurrence rate Galactography (Hou MF.Radiology 1995:195:568-9) (Hou MF. Clin Imaging 1998,22:89-94) (Hou MF.Acta Cyto 2000,44: ) (Hou MF. J Cli Imag 2001,25:75-81) (Hou MF.The Breast,2002,11: ) MRM 16 0 Ductolobular resections 19 0 Follow-up 8 yrs (Hou MF.Radiology 1995:195:568-9) (Hou MF. Clin Imaging 1998,22:89-94) (Hou MF.Acta Cyto 2000,44: ) (Hou MF. J Cli Imag 2001,25:75-81) (Hou MF.The Breast,2002,11: ) Oncoplastic Breast Surgery Radial-excision lumpectomy Donut mastopexy lumpectomy Batwing mastopexy lumpectomy Breast reduction lumpectomy Breast Reconstruction after Mastectomy Timing of reconstruction 1. Immediate reconstruction 2. Delay reconstruction Types of reconstruction 1. Implant reconstruction a. 20% Implant complication (infection, rupture, extrusion, capsular contracture, autoimmune?) b. Tissue expander 2.Autogenous Reconstruction TRAM Flap (Transverse rectus abdominis muscle) Free or pedicle; Latissimus dorsi flap 3. Mastectomy a. Conventional non-skin sparing Hou MF, Lin b. Skin sparing SD. c. Nipple-areolar preservation Authors yrs No. of p ts Recurre nce rate % F/u yrs 1. Noone R.B Slavin S.A.l Carlson G.W * Newman L.A * Langstein l Carlson l Spiegel l * 3.1(16/5 03) 5.7 (BO Anderson,Lancet Oncol 2005; 6: ) Radiotherapy 放射線治療 乳房部份切除併放射線治療 RT Reduces Local Recurrences Breast Conservation Mastectomy 乳房部份切除併加速部份放射線治療 Accelerated Partial Breast Irradiation 減少放射線暴露減少組織傷害縮短時間 Targit Mammosite 局部再發高但存活率相似 EBCTCG, Lancet, 2005, 366:

12 Breast Cancer Histologic Classifications Carcinoma, NOS (not otherwise specified). Ductal. Intraductal (in situ). Invasive with predominant intraductal component. Invasive, NOS. Comedo. Inflammatory. Medullary with lymphocytic infiltrate. Infiltrating or invasive ductal Mucinous (colloid). cancer is the most common breast Papillary. cancer histologic type and Scirrhous. comprises 70% to 80% of all cases. Tubular. Other. Lobular. In situ. Invasive with predominant in situ component. Invasive. Nipple. Paget s disease, NOS. Paget s disease with intraductal carcinoma. Paget s disease with invasive ductal carcinoma. Other. Undifferentiated carcinoma. The following are tumor subtypes that occur in the breast but are not considered to be typical breast cancers: Cystosarcoma phyllodes;angiosarcoma;primary lymphoma. 5-Year Breast Cancer Relative Survival Rates (SEER) According to Tumor Size and Lymph Node Status 治療個人化及共識化 Continuing Progress in Breast Cancer Treatment: Moving Toward Molecular Oncology Survival Rate, % Primary Tumor Diameter, cm SEER = Surveillance, Epidemiology, and End Results Program. Carter et al. Cancer. 1989;63: No nodal involvement 1 3 Positive nodes 4 Positive nodes Empirical Oncology 2008~2012 Rough estimation of relapse risk One shoe fits all Treatment strategy Chemotherapy Hormone agents Tumor size Nodes Tumor grade Histological type Age Performance status ER (Tamoxifen,AI) PR Proliferation markers (TLI, Ki-67, MIB-1, PCNA) Apoptotic index Molecular Oncology Antibodies, Target agents Improved estimation of relapse risk Heterogeneous Tailored adjuvant treatment Data Evidence and Consensus for Adjuvant Therapy ( Early Breast Cancer) 乳癌治療共識會議指引 NIH consensus conference (2000) Early Breast Cancer Trialists Collaborative Group (EBCTCG, Oxford Overview) (2007, 2010) St. Gallen International Consensus Panel on the Treatment of Primary Breast Cancer (2007, 2009-March) NCCN guideline (2010 v.2) San Antonia 2009 Dec Sotiriou C,& Pusztain L NEJM 360;8, 2009

13 Predictive Factor: Sensitivity for Therapy Key Factors: Endocrine Therapy ER expression PR HER2 Ki 67 Grade Recurrence Score/ signature Chemotherapy Tailored Adjuvant Therapy for HER2 Negative Breast Cancer Tumor Subtype Risk Factors Adjuvant Endocrine Adjuvant Chemotherapy Triple negative Stage Not applicable Anthracycline-and taxane-based Hormone-receptor positive Lower risk Strong ER/PR Lower grade Node negative Limited/ absent LVI Smaller T size Lower recurrence score Higher risk Lower ER/PR Higher grade Nodal involvement LVI Larger T size Higher recurrence score Postmenopausal: Tam AI vs AI alone vs Tam alone Premenopausal Tam+/- OS Likely minimal role for chemotherapy Anthracyclin-and taxane-based Adjuvant Therapy in BC NCCN 2010 N-,>1cm E+CT+H E±CT* CT+H CT IDC ER+,H+ ER+,H- ER-,H+ ER-,H- N-,<0.5cm E (mic)c E (mic) CT (mic) CT (mic) N-,0.6~1.0cm E±CT±H E ±CT* CT±H CT N+ E+CT+H E+CT CT+H CT Favorable (Tubular, ER+ ER- Colloid) N-,<1cm No No N-,1~2.9cm Ec CTc N-, 3cm E CT N+ E±CT CT+H CT CT: chemotherapy; E: endocrine therapy; c:consider; mic:microinvasion; H:Her2/Herceptin Modified by MF Hou 2010 April *(Gene 21): None: E±CT RS<18: E RS18~30: E±CT RS>31:E+CT St Gallen Consensus 2009 Thresholds for treatment modalities Next slide Ann Oncol Aug;20(8):

14 St Gallen Consensus 2009 Chemoendocrine therapy in patients with ER-positive, HER2-negative disease International Overview Results of Adjuvant Ovarian Ablation, Tamoxifen and Chemotherapy Relative Recurrence Reduction Mortality Ann Oncol Aug;20(8): OA vs Control 25 ±7 % 24 ±7 % OA + C/T vs C/T 10 ±9 % 8 ±10 % C/T vs Control 37 ±4 % 28 ±5 % Tam 5 yr vs Control 47 ±5 % 26 ±4 % (Lancet 1996; 348:1189) (Lancet 1998; 353:930) (Lancet May;365: ) Molecular Subtypes of Breast Cancer Molecular Subtypes of Breast Cancer : Relative Benefits of Therapy Type Hormone Receptor Positive (ER/PR) Her2 Positive Triple Negative Interventions Antiestrogen therapies Chemotherapy Trastuzumab Chemotherapy Chemotherapy Type Interventions Anti-E Chemo Trastuzumab ER+/PR % 20-35%** ER+/PR- 33% 20-35% Her2+/ER+ ~33% 20-35% ~50% Her2+/ER % ~50% Triple Negative % 2nd Asia International Breast Cancer Summit 2208 July Hangzhou *Tamoxifen 47%; AI ~57% **Low aggressive~20%, Aggressive ~35% 核心的定義與意涵 乳癌核心介紹 核心 (Core Measures), 係指一組標準化的績效, 可被一致性的使用於各醫療照護組織並做為臨床品質指標測量系統 核心測量以組為單位是由同一領域 ( 如 : 乳癌 ) 內多個相互關聯之品質指標所組成 可幫助醫療機構確認品質改善的機會, 並提供整合性資訊協助外部人員或管理者對該機構進行整體性的評估, 近一步了解其照護品質之全貌

15 乳癌核心發展 國家癌症防治五年計畫 : 建立主要癌症之核心, 推動癌症醫療遵循準則提升並確保診療品質 乳癌核心 ~ 治療前 發展醫療品質指標所必備的六項關鍵的步驟 : 1. 確認測量領域 目的及使用者 2. 組成多元專家小組 3. 收集實證醫學支持的候選指標清單 4. 透過專家共識法進行指標選擇 5. 進行實施前測試 6. 撰寫計分結果與分析規格 專責單位行政院衛生署國民健康局 50 歲以上 ( 含 ) 婦女施行乳癌手術前 3 個月內有雙側乳房 x 光攝影的比率 分子 :50 歲以上施行乳癌手術前 3 個月內有雙側乳房 x 光攝影的人數 分母 :50 歲以上施行乳癌手術人數 69.2% 83.51% 乳癌核心 ~ 治療前 乳癌核心 ~ 治療 乳癌病人在手術進行前曾經細胞學或組織學診斷的比率 分子 : 乳癌病人在手術進行至少前一天曾經細胞學或組織學診斷的人數 ( 排除 : 轉移性乳癌病人與同一天病人 ) 分母 : 經過手術治療的乳癌病人 72.8% 81.0% 確診結果為乳癌者, 於 2 個月內接受治療的比率 分子 : 確診結果為乳癌者且 2 個月內接受治療的人數 分母 : 確診結果為乳癌者人數 97.0% 97.8% 乳癌核心 ~ 診療 乳癌核心 ~ 診療 乳癌第零期且病理報告清除腋下淋巴結數 10 顆以上的比率 分子 : 第零期且病理報告接受清除腋下淋巴結數 10 顆以上的病人數 分母 : 第零期腫瘤 2.5 公分以下的病人數 ( 排除 : 接受手術前化學治療或放射線治療或轉移性乳癌病人 ) 26.7% 25.0% 乳癌第 I 期執行乳房保留手術的比率 分子 : 第 I 期乳癌且接受乳房保留手術的人數 分母 : 第 I 期乳癌的人數 乳癌第 II 期執行乳房保留手術的比率 分子 : 第 II 期乳癌且接受乳房保留手術的人數 分母 : 第 II 期乳癌的人數 52.6% 52.4% 35.0%

16 乳癌核心 ~ 診療 乳癌病人手術後病理檢查報告記錄原發腫瘤大小的比率 分子 : 病理檢查呈現主要腫瘤大小的病理報告總人數 分母 : 病理報告總人數 ( 排除 : 轉移性乳癌病人 ) 94.3% 94.1% 乳癌核心 ~ 診療 侵犯性乳癌在切除腫瘤時, 病理檢查 10 個或以上的腋下淋巴結廓清的比率 分子 : 病理檢查 10 個或以上腋下淋巴結人數 分母 : 手術合併清除腋下淋巴結的病人數 ( 排除 : 接受術前化放療或轉移性乳癌病人與及 Sentinel node biopsy) 73.4% 81.5% 乳癌核心 ~ 診療 侵犯性乳癌, 有 ER 接受體報告的比率 分子 : 檢查報告有 ER 接受體分析結果病人數 分母 : 有病理檢查報告的病人數 侵犯性乳癌, 有 PR 接受體報告的比率 分子 : 檢查報告有 PR 接受體分析結果病人數 分母 : 有病理檢查報告的病人數 96.7% 96.9% 96.9% 乳癌核心 ~ 診療 侵犯性乳癌, 有 Her2 接受體報告的比率 分子 : 檢查報告有 Her2 接受體分析結果病人數 分母 : 有病理檢查報告的病人數 97.6% 96.4% 乳癌核心 ~ 診療 侵犯性乳癌乳房保留手術後放射治療的比率 分子 : 侵犯性乳癌接受乳房保留手術後放射線治療的人數 分母 : 侵犯性乳癌接受乳房保留手術的人數 70.5% 77.0% 乳癌核心 ~ 診療 停經前 ( 50 歲 ) 婦女腋下淋巴結陽性的乳癌病人給予輔助性化學治療 分子 : 停經前婦女腋下淋巴結陽性的病人給予輔助性化學治療的病人數 分母 : 停經前婦女腋下淋巴結陽性的病人數 ( 排除 : 轉移性乳癌病人 ) 83.9% 97.2%

17 乳癌核心 ~ 診療 乳癌核心 ~ 存活分析 (2004 年 年整體存活率 ( 依整併分期 )) 停經後 (>50 歲 ) 婦女腋下淋巴結陽性的乳癌病人給予賀爾蒙治療或輔助性化學治療 分子 : 停經後婦女腋下淋巴結陽性的病人給予賀爾蒙治療或輔助性化學治療人數 分母 : 停經後婦女腋下淋巴結陽性的病人數 90.9% 100% 整併分期 1 年存活率 (%) 3 年存活率 (%) 5 年存活率 (%) Stage 0 100% 100% 98.4% Stage I 100% 97.3% 93.2% Stage IIA 99.6% 93.4% 87.0% Stage IIB 100% 89.7% 84.6% Stage IIIA 100% 86.7% 70.6% Stage IIIB 95.2% 75.6% 75.6% Stage IIIC 96.4% 77.8% 67.8% Stage IV 68.7% 31.2% 31.2% 乳癌核心 ~ 存活分析 (2004 年 年整體存活率 ( 依整併分期 )) 整併分期 1 年存活率 (%) 3 年存活率 (%) 5 年存活率 (%) Stage 0 100% 100% 98.4% Stage I 100% 97.3% 93.2% Stage IIA 99.7% 93.9% 87.5% Stage IIB 100% 90.4% 85.2% Stage IIIA 100% 85.5% 69.7% Stage IIIB 95.7% 76.1% 76.1% Stage IIIC 97.1% 79.4% 69.2% Stage IV 73.2% 35.0% 35.0% Church of Santa Maria della Grazia that Jayant S. Vaidya The Breast accepted 19 September 2006 houses Leonardo da Vinci s Last Supper 2008-Sep-2 8th Milan Breast Cancer conference, 100