prof g. sivakumar, emeritus professor of surgery & retired hod of surgery madras medical college...
TRANSCRIPT
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Prof G . SIVAKUMAR,Emeritus Professor of Surgery
&Retired HOD of Surgery
MADRAS MEDICAL COLLEGECHENNAI
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Hippocrates, was sceptical about any intervention for cancers of the breast, saying that
" It is better to give no treatment in the cases of hidden cancer. Treatment causes speedy death, but to omit treatment is to prolong life"
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Diagnosis of Breast CancerDiagnosis of Breast Cancer
TNM Staging:
Survival at 10 years
I: Early
90%
II: Operable
60%
III: Locally Advanced 30%
IV: Metastatic 5%
97% survive more than 5 years if diagnosed at an early stage.
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Carcinoma BreastManagement of Early Ca Stage I & II
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Population screeningACS guidelines
Population screeningACS guidelines
Annual screening mammogram +40 yrs
Physical examination
Monthly BSE
Earlier in risk group
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TUMOUR DOUBLING TIME
100-300 days
“CA BREAST IS A SYSTEMIC DISEASE”
B. FISCHER
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IDENTIFYING THE WOMAN AT RISK
AGE - HORMONES – HERIDITORY - HISTOLOGY
IDENTIFYING THE WOMAN AT RISK
AGE - HORMONES – HERIDITORY - HISTOLOGY
AGE & Ca BREASTIncidence more & Prognos is Better
Endogenous & Exogenous EstrogenHormonal replacementOral Contraceptives
GeneticsBRCA-1BRCA-2P53, Rb-1Her-2/neu, c-erB2, c-myc
Proliferative changesDuctal and Lobular HyperplasiaAtypical Ductal and Lobular HyperplasiaLCIS
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Genetic studies
Germline mutation
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Genetic RiskGenetic Risk2 Genes have been identified that whenmutated increase riskBRCA1 (chromosome 17)BRCA2 (chromosome 13)
Only 10% of all breast cancer is associated with an identifiable genetic mutation.
A woman with an identifiable genetic mutation may have –90% lifetime risk of ca breast50% chance of opposite breast and20% of ovarian ca
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Family History of Cancer Breast Cancer Risks
Family History of Cancer Breast Cancer Risks
Risk Factor-Mother or sister breast cancer
-If both sides or premenopausal diagnosis
-If both sides or age<40
-Mother and sister
Both sides and age<40
-No children or 1st pregnancy >30
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Genetic aspects - BRCA1
Screening protocol from 25 yrsProphylactic mastectomy- oophorectomy
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SOMATIC
MUTATION
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Risks for Breast CancerRisks for Breast Cancer
GAIL Model to
IDENTIFY THE HIGH RISK GROUP
Early screeningChemoprevention with Tamoxifen
Prophylactic mastectomy
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Breast Cancer Continuum: intervention possibilitiesBreast Cancer Continuum: intervention possibilities
Prevention of ClinicallyDetectable Breast CancerPrevention of Clinically
Detectable Breast Cancer
Pre- Malignant Conditions
LCIS 6.5%ADH 5.1%
Women at Increased Risk
1.7 % to 14%
Non- Invasive Cancer
DCIS 7.2%
Prevention of Contralateral Breast Cancer 3.2%
Prevention of Contralateral Breast Cancer 3.2%
Tumors< 1cm
11.8%
Early Stage
node neg25.1%
Early Stage
node pos47.1%
Prevention of Recurrence
Late StageCancer
Recurrenceof BreastCancer
Prevention of Progression
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Stages of tumour developmentStages of tumour development
Malignant cell
Dissemination of other organs
Invasion
Proliferation Angiogenesis
Neovascular endothelial
maintenance
Invasion
CytotoxicsEndocrineEGFR inhibitorsHER2 antibodies
Anti-angiogenics
Vasculartargeting agents Novel
agentsNovelagents
MetastaticCancer
of other organs
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Proliferative changes
Ductal and Lobular Hyperplasia
Atypical Ductal and Lobular Hyperplasia
LCIS
Proliferative changes
Ductal and Lobular Hyperplasia
Atypical Ductal and Lobular Hyperplasia
LCIS
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Benign Breast disease - Relative RiskBenign Breast disease - Relative Risk
Risk FactorProliferative Benign breast disease
Moderate Hyperplasia 2Atypical Hyperplasia 4Atypical Hyperplasia and FH 11
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Pick up to 24% high risk patients with normal imaging 3.2 times more than cytology of nipple discharge alone.
Dooley WC, Journal of National Cancer institute, 2001
Ductoscopy & Ductal lavage cytology
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Types of breast cancerTypes of breast cancer
In situIntraductal (DCIS)
Intralobular (LCIS)
InvasiveInfiltrating ductal carcinoma
Tubular carcinoma
Medullary carcinoma
Mucinous carcinoma
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Clues to exclude Non malignant conditionsClues to exclude Non malignant conditions
Fibroadenoma Young, mobile from breast tissue
Breast abscess Lactating, Inflammatoy features
F C B Middle age, Bilateral, Cyclical pain
Tuberculosis Breast Sinuses and pthisis
Skin tumours
Hidradenitis
Fatty pectoral fold
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Clinical signs and symptomsClinical signs and symptoms
Lump features
Puckering
Dimpling
Retraction
Nipple discharge
Thickening of skin or lump or “knot”
Retracted nipple
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Clinical signs and symptomsClinical signs and symptoms
Change in breast size
Pain or tenderness
Redness
Change in nipple position
Scaling around nipples
Sore on breast that does not heal
PAGET’S DISEASE
PAGET’S DISEASE
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Mammographic abnormalitiesMammographic abnormalities
Spiculated masses
Clustered calcification
Architectural distortion
Pleomorphic calcification
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Micro calcificationLe Gal’s classification
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The Breast Imaging Reporting and Data System (BI-RADS)
0 Incomplete assessment1 Negative2 Benign finding3 Probably benign finding4 Suspicious abnormality5 Highly suggestive of malignancy6 Known biopsy—proven malignancy
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Ductal Carcinoma in situ (DCIS)
Ductal Carcinoma in situ (DCIS)
Increased incidence due to screening
FNAC is not useful
Comedo vs non comedo
Surgical exision
Axillary clearance not necessary
Van Nuys prognostic index
LCIS requires observation
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Multicentricity and MultifocalityMulticentricity and Multifocality
Multicentricity
Multicentricity in breast cancer may be defined as the presence of two or more tumor foci within a single quadrant of the breast.
Multifocality
Multifocality in breast cancer may be defined as the presence of two or more tumor foci within different quadrants of the same breast.
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Types of DCISTypes of DCIS
Traditionally based on Morphological features Five types: comedo 30-50% solid 9-20% cribriform 20-25% micropapillary 8-14% Papillary 4-7%
Van Nuys Prognostic Index Van Nuys Prognostic Index
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DCIS - Ductal Carcinoma in SituDCIS - Ductal Carcinoma in Situ
Mastectomy is acceptable No Axillary node dissection
BCT is an acceptable approach if:Lesion is small (< 3 cm)
Margins must be negative preferably > 10 mm in all dimensions
Nuclear grade is low to intermediate
Adjuvant radiotherapy can be delivered
Surgery alone can be considered if margins >10 mmcontroversial
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BIOPSYBIOPSYA – PALPABLE LESIONS
FNAC
DIAGNOSTIC MAMMOGRAPHY+ USG OR STEREOTACTIC LOCALIZATION + FNAC = 100% DIAGNOSTIC
CORE BIOPSY
EXCISIONAL BIOPSY
NEWER BIOPSY TECHNIQUES
Mammotome
B – NON PALPABLE LESION
Image guided biopsies
USG guided FNAC or core needle biopsy
STEREOTACTIC needle biopsy
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Sterotactic biopsy
Hooked wire
Vacuum assisted biopsy
I125 seed localisation
Nonpalpable lesions
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FNACSENSITIVITY > 90%
CYTOLOGY
ER & PgR can be Estimated
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Staging of Breast CancerStaging of Breast CancerThe American Joint Committee on Cancer (AJCC)
has designated staging by TNM
7th edition
T= tumor size
N = lymph node involvement
M = metastasis
TX - T0 - Tis - T1, T2, T3, T4 NX - N0 -N1, N2, N3 MX - M0 - M1
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TX Primary tumor cannot be assessedT0 No evidence of primary tumorTis Carcinoma in situTis (DCIS) Ductal carcinoma in situTis (LCIS) Lobular carcinoma in situTis (Paget) Paget disease of the nipple NOT associated with invasive carcinoma and/or carcinoma in
situ (DCIS and/or LCIS) in the underlying breast parenchyma. Carcinomas in the breast parenchyma associated with Paget disease are categorized based on the size and characteristics of the parenchymal disease, although the presence of Paget disease should still be noted
T1 Tumor ≤ 20 mm in greatest dimensionT1mi Tumor ≤ 1 mm in greatest dimensionT1a Tumor > 1 mm but ≤ 5 mm in greatest dimensionT1b Tumor > 5 mm but ≤ 10 mm in greatest dimensionT1c Tumor > 10 mm but ≤ 20 mm in greatest dimensionT2 Tumor > 20 mm but ≤ 50 mm in greatest dimensionT3 Tumor > 50 mm in greatest dimensionT4 Tumor of any size with direct extension to the chest wall and/or to the skin
T4a Extension to chest wall, not including only pectoralis muscle adherence/invasion
T4b Ulceration and/or ipsilateral satellite nodules and/or edema (including peau d’orange) of the skin, which do not meet the criteria for inflammatory carcinoma
T4c Both T4a and T4bT4d Inflammatory carcinoma
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NX Regional lymph nodes cannot be assessed (eg, previously removed)N0 No regional lymph node metastasisN1 Metastasis to movable ipsilateral level I, II axillary lymph node(s)N2 Metastases in ipsilateral level I, II axillary lymph nodes that are clinically
fixed or matted or in clinically detected* ipsilateral internal mammary nodes in the absence of clinically evident axillary lymph node metastasis
N2a Metastases in ipsilateral level I, II axillary lymph nodes fixed to one another (matted) or to other structures
N2b Metastases only in clinically detected* ipsilateral internal mammary nodes and in the absence of clinically evident level I, II axillary lymph node metastases
N3 Metastases in ipsilateral infraclavicular (level III axillary) lymph node(s), with or without level I, II axillary node involvement, or in clinically detected * ipsilateral internal mammary lymph node(s) and in the presence of clinically evident level I, II axillary lymph node metastasis; or metastasis in ipsilateral supraclavicular lymph node(s), with or without axillary or internal mammary lymph node involvement
N3a Metastasis in ipsilateral infraclavicular lymph node(s)N3b Metastasis in ipsilateral internal mammary lymph node(s) and axillary lymph
node(s)N3c Metastasis in ipsilateral supraclavicular lymph node(s)
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On January 1, 2010,the new 7th edition of the AJCC staging system for breast cancer went into effect.
Summary of Changes to 7th Edition AJCC
The changes can be divided into 4 areas:Tumor size definitionNode classificationMetastasis classificationSpecial issues in patients who received neoadjuvant chemotherapyM0(i +) No larger than 0.2 mm of cancer cells are found in blood or bone marrow or in lymph nodes away from the breast
.
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ANATOMIC STAGE PROGNOSTIC GROUP
0 Tis N0 M0IA T1 N0 M0
IBT0 N1mi M0T1 N1mi M0
IIAT0 N1 M0T1 N1 M0T2 N0 M0
IIBT2 N1 M0T3 N0 M0
IIIA
T0 N2 M0T1 N2 M0T2 N2 M0T3 N1 M0T3 N2 M0
IIIBT4 N0 M0T4 N1 M0T4 N2 M0
IIIC Any T N3 M0IV Any T Any N M1 (cM0(i+)
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Principle of TherapyPrinciple of Therapy
Cure - Add Years to Life
Survival /Disease Free Interval
Palliation - Add Life to Years
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Clinical staging – TNM -AJCClinical staging – TNM -AJC
Stage I Early Cancer clearance
Stage II Operable Cancer clearance
Stage III Locally adv Downstage
Stage IV MetastaticPalliation
Stage I & II Curative Surgery with Adjuvant therapy
Stage III Neo Adjuvant therapy
Stage IV Systemic therapy
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Paradigm shift in Breast cancer treatmentParadigm shift in Breast cancer treatment
B. Fischer “ca breast is a systemic disease”
William Halsted “Local Radical Therapy”
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Radical Mastectomy - HalstedRadical Mastectomy - Halsted
Locoregional clearance Breast with nipple areola, Skin, PMj & PMn, Costocorocoid membrane.
Axillary nodes fascia & fat
Preserve
Axillary vessels, Cephalic vein & Nerve of Bell, nerve to Latissimus dorsi
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Surgical ManagementSurgical Management
M R M
Total mastectomy with
Axillary Dissection
BCT - QUART
Quadantectomy
with
Axillary Dissection
with
Radiotherpy
RADIOTHERAPY IS A MUST
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Breast Conserving Therapy - BCTBreast Conserving Therapy - BCT
70-80% of patients with stage I or II disease are candidates for BCT
6 major randomized trials comparing mastectomy to BCT No difference in DFS No difference in OS
Trial # Time pt. Mast. BCT
WHO 1972-79 179 22 yrs 24% 23%
Milan I 1973-80 701 20 51% 54%
NSABP06
1976-84 1406 20 33% 40%
US NCI 1979-89 279 20 34% 39%
EORTC 10801
1980-86 903 10 34% 30%
Denmark 82TM
1983-89 859 6 32% 34%
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Management of Axillary Nodes Levels I, II & III
Management of Axillary Nodes Levels I, II & III
“ Node involvement is of Great
Prognostic value but Axillary clearance
is of no value in survival ’’
SENTINEL NODE BIOPSY
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SENTINEL Node BiopsyLYMPHAZURIN BLUE
DYE
Tc99 SULPHUR COLLOID
Accuracy 99%
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Management of Mastectomy Specimen
Management of Mastectomy Specimen
HPE Grading
Margins
Ax Nodes – IM ?
Receptors
Her2/neu
DNA content
S - phase fraction
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ESTROGEN RECEPTOR STATUS
Pg Receptor &
HER-2/neu
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HER2/neu
Overexpression
Herceptin
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The outer layer is called the basal layer and the inner layer is called the luminal layer.
Triple-negativeBreast cancers
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Stage I & II Adjuvant therapyStage I & II Adjuvant therapy
Hormonal
Chemotherapy
Radiotherapy
Aromatase inhibitors
Herceptin
Biphosphonates
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Adjuvant systemic therapyStage I & Stage II
Adjuvant systemic therapyStage I & Stage II
PREMENOPAUSAL POSTMENOPAUSAL
ER+ CHEMOTHERAPY/OVARIAN ABLATION/TAMOXIFEN
TAMOXIFEN +/- CHEMOTHERAPY
ER- CHEMOTHERAPY CHEMOTHERAPY
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Cell cycle and cytotoxic opportunities
CELLDIFFERENTIATION
CELLLIFE CYCLE
TIME
CELLDIVISION
G2 PERIOD
(CHROMOSOME REPLICATION) S-PHASE
G1 PERIOD
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Hormonal Managemrnt of Carcinoma Breast
Sir George Beatson
Oophorectomy
TAMOXIFENAROMATASE INHIBITORS
Hormonal Managemrnt of Carcinoma Breast
Sir George Beatson
Oophorectomy
TAMOXIFENAROMATASE INHIBITORS
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Selective inhibitors
Nonselective inhibitorsMultiple steps involving P-450 enzymes and production of steroid
intermediates
Cholesterol
Cortisol AndrostenedioneAldosterone
Testosterone
Estrone Estradiol
Federman, DD. The adrenal. Scientific American Medicine. Dale DC, Federman DD, eds. Section 3. Subsection IV. ©1997 Scientific American Inc. All rights reserved.
Selective vs Nonselective Aromatase InhibitionSelective vs Nonselective Aromatase Inhibition
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Disruption of cadherin junctions
Focal contact/adhesion turnover
GPCR signalingcross-talk
RTK phosphorylation signal modulation and cross-talk
Cytoskeleton
ApoptosisProliferation
ba
SRC
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If getting chemotherapy…If getting chemotherapy…
Radiation is usually withheld until after the systemic therapy is complete.
Followed with Hormonal therapy if indicated
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Post-mastectomy Radiotherapy
Chest wall:
- 4 or more pathologically involved axillary
nodes,
- primary tumor >5cm(large breast)
- and tumor 3-5cm( small breast),
- narrow deep margin <0.5cm,
- evidence of lymph vascular invasion.
Irradiation to the axilla is only for those who have not had axillary clearance.
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RT as Adjuvant
Radio therapy & BCT
RT as Adjuvant
Radio therapy & BCT
48% vs34%
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Breast Reconstruction
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BREAST RECONSTRUCTION
TRAM
&
LD
FLAPS
ONCO PLASTIC SURGERY
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Management of Advanced Ca Breast
LABC & Systemic disease
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AJCC defines inflammatory carcinoma as a clinical entity.
Staging as pT4d
Diffuse erythema and edema involving a third or more of the skin of the breast.
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