乳腺癌中山大学肿瘤医院20101019

Breast Cancer,Xiaoming Xie, M.D. and Ph.D.Department of Breast OncologySun Yat-Sen University Cancer Center谢小明 中山大学肿瘤防治中心 乳腺科 Email: Tel: 61639540 (O)，(Cell),Jemal A., et al. CA Cancer J Clin 2010; 60:277-300,Breast cancer is the most common cancer and the second leading cause of cancer-related death for women in USA,Jemal A., et al. CA Cancer J Clin 2010; 60:277-300,Death Rates For Cancer and Heart Disease for Ages Younger Than 85 Years and 85 Years and Older, 1975 to 2006,Breast cancer is more frequently diagnosed in affluent countries and the death rate is higher in developing countries,Recent Decrease in UK and USA Breast Cancer Mortality at Ages 5069 Years,Modified from Peto et al. Lancet 355:1822, 2000,Functional Anatomy,Blood Supply,(1) perforating branches of the internal mammary artery; (2) lateral branches of the posterior intercostal arteries(3,4,5); (3) branches from the axillary artery, including the highest thoracic, lateral thoracic （胸外侧动脉）, and pectoral branches of the thoracoacromial artery 肩胛下动脉：此血管不供血于乳腺，但作乳癌根治术时需清除其周围的淋巴结，术中易损伤，需小心操作、必要时可结扎、切断。,The veins of the breast and chest wall,The three principal groups of veins (1) perforating branches of the internal thoracic vein; (2) perforating branches of the posterior intercostal veins; (3) tributaries of the axillary vein. The vertebral venous plexus of Batson, which invests the vertebrae and extends from the base of the skull to the sacrum, may provide a route for breast cancer metastases to the vertebrae, skull, pelvic bones, and central nervous system. Lymph vessels generally parallel the course of blood vessels.,肋间-椎静脉系转移(骨，肺，肝，脑）,Neural anatomy of the breast,Lateral cutaneous branches of the third through sixth intercostal nerves provide sensory innervationLateral pectoral n.Medial pectoral n. Long Thoracic n.(胸长N) supply the serratus anterior muscle. “winging of the scapula and loss of shoulder power（紧贴胸壁下行，支配前据肌)Thoracodorsal n. (胸背N) （approach subscapular artery）: supply latissimus dorsi muscle（肩胛下血管伴行，支配肩胛下肌、大圆肌）,The lymphatic drainage of the breast,75%,20-25%,The lymph node groups,1. level I LN(14-19). located lateral to or below the lower border of the pectoralis minor muscle: the axillary vein（4-6): external mammary（5-6), scapular groups （5-7）2. Level II LN (5-8): located superficial or deep to the pectoralis minor muscle the central(3-4), interpectoral groups (Rotters）(1-4) 3. Level III LN : located medial to or above the upper border of the pectoralis minor muscle: the subclavicular group（6-12),Risk factors - unchangeable,1. Being a woman: 1 out of 8 in lifetime，男性乳腺癌仅占乳腺癌的1%左右2. Age: increasing over age, 1790岁，中位年龄47岁。按5岁年龄段计算，4549岁的患者最多（25.2），次为4044岁（15.8）和5954岁（15.6） 3. Genetic factors - mutations in BRCA1 or BRCA2; 50-60% of women inheriting a BRCA1 mutation from either parent will have breast cancer by age 70: collaboration with Dr. Bignon, France4. Family history of breast cancer (not related to BRCA mutations): we are testing 18 genes5. Personal history of hyperplastic breast disease,Risk factors - unchangeable/contd.,6. Personal history of breast cancer7. Race: incidence is higher in Caucasian compared with African-American, Hispanic or Asian women8. Radiation treatment: chest irradiation as a child/young woman can significantly increase risk of developing breast cancer9. Dense breast tissue10. Menstrual history: early menarche (50yr) has some association with increased risk. Also nulliparous, or first childbirth at 30 yrs,Risk factors associated with lifestyle,1. Oral contraceptives - remains controversialHormone replacement therapy - 5 years of therapy with combined estrogen and progesterone may increase risk Not breast feeding4. Obesity, lack of physical activity5. Alcohol - 2-5 drinks/day can increase risk x 1.5 over non-drinkers.,Factors with uncertain, controversial or unproven effects on risk of developing breast cancer,High fat diet Induced abortionsBreast implantsEnvironmental chemical exposure (e.g. pesticides)Tobacco smokeNight shift workHuman mammary tumor virus ?,Hereditary Breast Cancer,Hereditary breast-ovarian cancer (HBOC) syndrome：Mutation in BRCA1, BRCA2 genesAtaxia telangiectasia (A-T) : Mutation in ATM geneLi-Fraumeni syndrome: Mutation in p53 gene (? CHEK2 gene).Cowden syndrome: Mutation in PTEN genePeutz-Jeghers syndrome: Mutation in STK11 gene,Histopathology of Breast Cancer,Carcinoma In Situ,Ductal carcinoma in situ (DCIS) cribriform type,Ductal carcinoma in situ (DCIS) cemedo type,Lobular carcinoma in situ (LCIS),Invasive Breast Carcinoma,Pagets disease of the nippleInvasive ductal carcinoma.A. Adenocarcinoma with productive fibrosis (scirrhous, simplex, NST) 80%B. Medullary carcinoma 4%C. Mucinous (colloid) carcinoma 2%D. Papillary carcinoma 2%E. Tubular carcinoma (and ICC) 2%3） Invasive lobular carcinoma 10%4） Rare cancers (adenoid cystic, squamous cell, apocrine),Invasive ductal carcinoma,Infiltrating lobular carcinoma,Blood vessel invasion,Lymphatic invasion,Microinvasive breast cancer （微侵）,The extension of cancer cells beyond the basement membrane into the adjacent tissues with no focus greater than 0.1 cm in its greatest dimension.Stage: T1mic.Can be seen in association with DCIS and LCISFirst stage in the development of invasion.,Diagnosing breast cancer,Triple assessment,Clinical,Imaging,Pathology,AgeExamination,UltrasoundMammographyMRI,Fine needle aspiration cytologyCore-cut biopsy,Clinical Presentation,New lumps or a thickening in the breast or under the armNipple tenderness, discharge, or physical changesSkin irritation or changes (puckers, dimples, scaliness, or new creases),Symptoms that may indicate breast cancer,Lumps in the breast: single, hard and painless, irregular in shapeLumps in the armpitBreast pain: seldom (most the menstrual cycle, cyclic mastalgia)Bleeding or discharge from the nipple (5%)Involution or inversion of the nippleSwelling of the arm (lymphedema)Dimpling, ulceration of skinChanges in size or shape of the breastSymptoms of secondary tumors,A breast lump is most often the clinical problem that causes women to seek treatment and remain the most common presentation of breast carcinoma. 65% of breast cancer cases.Other less frequent presenting signs and symptoms of breast cancer include (1) breast enlargement or asymmetry; (2) nipple changes, retraction, or discharge; (3) ulceration or erythema of the skin of the breast; (4) an axillary mass; and (5) musculoskeletal discomfort. However, some of women presenting with breast complaints have no physical signs of breast pathology. Breast pain usually is associated with benign disease.,Lump,Dimpling （酒窝征）: skin retraction, tumors deep within the substance of the breast that involves the Coopers ligaments Peau dorange （桔皮征）: edema of the breast. Usually obstruction of the dermal lymphatics with tumor, extensive axillary LN involvement related met tumor, primary disease of the axillary nodes, axillary dissection. (also after irradiation of the breast).,Changes in the skin of the breast (DPUSE),Ulceration（菜花征）: in advanced case, the tumor may involve the skin, leading to it. Satellite change（卫星征）: tumor cells enter the lymphatic vessels and form masses around the primary site.,Erythema （炎症征）：inflammatory breast cancer, usually involves the entire breast and is distinguished from the inflammation due to infection by the absence of breast tenderness and fever.,Nipple retraction：tumor involves the tissue beneath the nipple. Bleeding: Eczematous change: PagetsChanges in the character of the skin.,The nipple change,Lymph nodes,Breast self-examination,Encourage Adverse effect: a lifetime of uncertainty and anxiety for the patient (of proven harm!)Controversy,Mammography,Annual screening mammography beginning at age 40 years is recommended in the United StatesMammography is shown to reduce mortality from breast cancer by as much as 44%American Cancer Society (ACS) 1997 Aged 40 Annual mammogram,Screening Mammography (cont.),Invasive cancer (4 mm),Malignant microcalcifications,Ultrasonography,Ultrasonography is an important method of resolving equivocal mammography findings, defining cystic masses, and demonstrating the echogenic qualities of specific solid abnormalities.Breast cysts are well circumscribed, with smooth margins and an echo-free centerBenign breast masses usually show smooth contours, round or oval shapes, weak internal echoes, and well-defined anterior and posterior marginsBreast cancer characteristically has irregular walls,乳腺癌沿Coopers韧带浸润50%，C3级,肿瘤穿破浅筋膜浅层和韧带已达皮下，C4级。,MRI,High sensitivity (94 100%)Low specificity (37 97%)Better “screening” tool than mammography in high-risk populationsExpensive, invasive and more time consuming,Breast Biopsy,1. Fine-needle aspiration (FNA) biopsy Sensitivity: 6598% Specificity: 34100% False-positive Rate: 0.17%2. Core-needle biopsy Automated biopsy gun (14-guage, 5 core samples for mass and 5-10 for microcalcification) Directional vacuum-assisted biopsy (Mammotome, EnCore) Stereotactic Core Biopsy Nonpalpable Lesion Sensitivity: 92100% Nonpalpable Lesion Imaging-guide Needle Localization3. Incisional or Excisional Biopsy,Biomarkers and Circulatory tumor cells,Carcinoembryonic antigen (CEA): positive rate 20%-70%.The MUC -1 gene product (CA15-3: positive 33-60%; CA27.29).(Ch 1q21-24).The HER-2/neuextrocellular domain (Ch 17q11-12). 20-30% overexpression.New serum tumor markers (uPA，urokinase plasminogen activator; PAI-1, plasminogen activator inhibitor-1).Circulatory tumor cells (CTC), 5 or more CTC cells in the blood of patients with MBC.,Comparative frequency of fibrocystic changes, fibroadenomas, and carcinomas by age groups,Staging,TNMHistologic type (DCIS, LDIS, IBC)Hormone receptors (ER,PR)Oncogenes (Her-2)Staging procedures,TNM staging,TNM Staging takes into account the size of the tumour (T); whether the lymph nodes (N) are affected and; whether the tumor has matastasized (M) anywhere else. The TNM system for staging is a frequently used staging system used all over the world. More likely to use this staging system because it describes stage more accurately than others.Treat breast cancer according to the staging and grade.,The T0 and Tis Stage,Tx: primary tumor cannot be assessedT0： No evidence of primary tumorTis: Carcinoma in situ Tis (DCIS), Ductal carcinoma in situ Tis (LCIS), lobular carcinoma in situ Tis (Pagets), pagets disease of the nipple with no tumor.,Modified from American Joint Committee on Cancer: AJCC Cancer Staging Manual, 6th ed. New York: Springer, 2002, pp 227228.,T1 Stage,T1mic: 0.1- 0.5 cmT1b: 0.5- 1.0 cmT1c: 1.0- 2.0 cm,T2 Stage,T2:2.0-0.5,T3 Stage,T3: 5.0 cm,T4 Stage,Tumor of any size with direct extension to (a) chest wall or (b) skin, only as described below T4a: The tumor is fixed to the chest wallT4b: The tumor is fixed to the skinT4c: T4a+T4bT4d: inflammatory carcinoma (red, swollen,and painful to the touch),Risk of Recurrence and Survival by Tumor Size for Patients with Node-Negative Disease,The N stage (clinical regional LN ）,Nx：Regional lymph nodes cannot be assessed (e.g., previously removed) .N0: No cancer cells found in any LN.N1: Metastasis to movable ipsilateral axillary LN.N2: N2a:Met in ipsilateral axillary LN fixed or matted or to other structures, N2b:Met only in clinically apparenta ipsilateral internal mammary LN and in the absence of clinically evident axillary LN met.N3: N3a:Met in ipsilateral infraclavicular LN. N3b: Met in ipsilateral internal mammary LN and axillary LN. N3c: Metastasis in ipsilateral supraclavicular LN.,0 12 24 36 48 60 72 84 96 108 120,Months,1.0,0.8,0.6,0.4,0.2,0.0,Proportion Relapse Free,Nodal Status,01-34-910+,Chang JC, Hilsenbeck SG in Dis of the Br 3rd Ed, p 673-696, 2004,Relapse Free Survival and Number of Involved Lymph Nodes,Lymph Node Metastasis and Survival,The N stage (pathologic regional LN）,pNx：Regional LN cannot be assessed (e.g., previously removed) pN0: No regional LN met histologically. pN0(i-),IHC; pN0(i+), IHC， no IHC cluster greater than 0.2 mm. pN0(mol-),RT-PCR; pN0(mol+), RT-PCR.pN1: Met in 1 to 3 axillary LN, and/or in internal mammary LN with microscopic disease detected by SLN dissection, not clinically apparent. pN1mi: Micrometastasis (greater than 0.2 mm, none greater than 2.0 mm) pNia: met in 1-3 axillary LN. pN1b: met in internal mammary LN with microscopic disease detected by SLN dissection pN1c: pNia+pN1b.pN2: Met in 4 to 9 axillary LN, or in clinically apparenta internal mammary LN in the absence of axillary lymph node metastasispN2a: Met in ipsilateral axillary LN fixed or matted to other structures, pN2b:Met only in clinically apparenta ipsilateral internal mammary LN and in the absence of clinically evident axillary LN met.pN3: Met in 10 or more axillary LN (pN3a), or in infraclavicular LN (pN3a), or in clinically apparenta ipsilateral internal mammary LN in the presence of 1 or more positive axillary LN; or in more than 3 axillary LN with clinically negative microscopic met in internal mammary LN (pN3b); or in ipsilateral supraclavicular LN (pN3c).,The M stage (distant metastasis),Mx: Distant metastasis cannot be assessed M0: No distant metastasis M1：Distant metastasis.,Stage and Grade,The stage of breast cancer means how far it has grown and whether it has spread. The grade means what the cancer cells look like under the microscope. Breast cancers can be grade 1 (Low grade or slow growing) grade 2( Intermediate grade ) grade 3 (High grade or fast growing),What the number staging system,Stage 0. Tis, N0, M0. Stage I. T1，N0, M0. When the cancer has spread beyond a milk duct or lobe, but not outside the breast. The tumor size for this stage is equal to or less than 2 cm.The tumour is no more than 2 cm across (T1) The LNin the armpit are not affected The cancer has not spread,Stage II,This is divided into two groupsStage IIA : T0,N1,M0; T1,N1,M0; T2,N0,M0; T1,N1,M0 : The tumour is less than 2 cm, the LN under the arm contain cancer but are not stuck to each other and the cancer has not spread. T2,N0,M0: The tumour is less than 5 cm, there are no cancer cells in LN in the armpit and the cancer has not spread. T0,N1,M0: Although no tumour is seen in the breast, the LN under the arm contain cancer cells but are not stuck together, and there is no sign of spread to other parts of the body.Stage IIB: T2,N1,M0; T3,N0,M0T2,N1,M0 : The tumour is less than 5 cm and the LN under the arm contain cancer cells but are not stuck to each other, and the cancer has not spread or T3,N0,M0 : The tumour is bigger than 5 cm across, there are no cancer cells in the lymph nodes in the armpit and the cancer has not spread,Stage III,Stage IIIA: T0,N2,M0; T1,N2,M0; T2,N2,M0;T3,N1,M0;T3,N2,M0. Although no tumour is seen in the breast, the lymph nodes under the arm contain cancer cells and are stuck together, but there is no sign of cancer spread or The tumour is 5 cm or less, the lymph nodes in the armpit contain cancer cells and are stuck to each other, but the cancer has not spread elsewhereor The tumour is more than 5 cm, the lymph nodes in the armpit contain cancer cells and may be stuck together, but there is no further spread.Stage IIIB: T4,N0,M0; T4,N1,M0; T4,N2,M0.The tumour is fixed to the skin or chest wall, the lymph nodes may or may not contain cancer cells, but there is no further spread.Stage IIIC: Ant T, N3, M0. The tumour can be any size and has spread to lymph nodes in the armpit and under the breast bone, or to nodes above or below the collarbone, but there is no further spread.,Stage IV,Stage IV. Ant T, any N, M1.Metastatic cancer, which is cancer that has spread to other more distantorgans of the body. Frequent metastatic sites for breast cancer are the bones, lungs, liver or brain. Stage IV is also the classification given to inflammatory breast cancer or breast cancer that has spread to the lymph nodes in the neck near the collarbone.The tumour can be any size The lymph nodes may or may not contain cancer cells The cancer has spread or metastasised to other parts of the body such as the lungs, liver or bones,Survival rate and prognosis factors,Stage Survival rate at 8 year(%)Stage 90Stage 70Stage 40Stage 10,Early Breast Cancer TNM Staging System,T0No evidence of primary tumorTisDuctal carcinoma in situ or lobular carcinoma in situT1Tumor 2 cmT2Tumor 2 cm but 5 cm,Greene FL, et al. AJCC Cancer Staging Manual, 6th ed., 2002.,Early Breast Cancer TNM Staging System (cont.),NXRegional lymph nodes cannot be assessedN0No involvement of regional lymph nodesN1Involvement of one to three axillary lymph nodesMXDistant metastases cannot be assessedM0No distant metastases,Stage Classifications for Early Stage Disease,Stage 0TisN0M0Stage IT1N0M0Stage IIAT0N1M0T1N1M0T2N0M0Stage IIB T2N1M0,Singletary SE, et al. J Clin Oncol. 2002;20:3576-3577.,Locally Advanced Breast Cancer （LABC）,This means the cancer has not spread to another part of the body but may be:Bigger than 5 cm across Growing into the skin or muscle of the chest Present in the lymph nodes in the armpit, and these lymph nodes are either stuck to each other, or other structures,NCCN 2010 Breast Cancer,Overall survival for women with breast cancer according to axillary lymph node status.,Risk of metastases according to breast cancer volume and diameter,Biomarkers of Breast cancer,Biomarkers and Circulatory tumor cells,Carcinoembryonic antigen (CEA): positive rate 20%-70%.The MUC -1 gene product (CA15-3: po