Prof G . SIVAKUMAR,Emeritus Professor of Surgery

&Retired HOD of Surgery

MADRAS MEDICAL COLLEGECHENNAI

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"

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.

Carcinoma BreastManagement of Early Ca Stage I & II

Population screeningACS guidelines

Population screeningACS guidelines

Annual screening mammogram +40 yrs

Physical examination

Monthly BSE

Earlier in risk group

TUMOUR DOUBLING TIME

100-300 days

“CA BREAST IS A SYSTEMIC DISEASE”

B. FISCHER

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

Genetic studies

Germline mutation

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

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

Genetic aspects - BRCA1

Screening protocol from 25 yrsProphylactic mastectomy- oophorectomy

SOMATIC

MUTATION

Risks for Breast CancerRisks for Breast Cancer

GAIL Model to

IDENTIFY THE HIGH RISK GROUP

Early screeningChemoprevention with Tamoxifen

Prophylactic mastectomy

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

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

Proliferative changes

Ductal and Lobular Hyperplasia

Atypical Ductal and Lobular Hyperplasia

LCIS

Proliferative changes

Ductal and Lobular Hyperplasia

Atypical Ductal and Lobular Hyperplasia

LCIS

Benign Breast disease - Relative RiskBenign Breast disease - Relative Risk

Risk FactorProliferative Benign breast disease

Moderate Hyperplasia 2Atypical Hyperplasia 4Atypical Hyperplasia and FH 11

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

Types of breast cancerTypes of breast cancer

In situIntraductal (DCIS)

Intralobular (LCIS)

InvasiveInfiltrating ductal carcinoma

Tubular carcinoma

Medullary carcinoma

Mucinous carcinoma

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

Clinical signs and symptomsClinical signs and symptoms

Lump features

Puckering

Dimpling

Retraction

Nipple discharge

Thickening of skin or lump or “knot”

Retracted nipple

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

Mammographic abnormalitiesMammographic abnormalities

Spiculated masses

Clustered calcification

Architectural distortion

Pleomorphic calcification

Micro calcificationLe Gal’s classification

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

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

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.

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

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

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

Sterotactic biopsy

Hooked wire

Vacuum assisted biopsy

I125 seed localisation

Nonpalpable lesions

FNACSENSITIVITY > 90%

CYTOLOGY

ER & PgR can be Estimated

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

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

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)

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

.

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+)

Principle of TherapyPrinciple of Therapy

Cure - Add Years to Life

Survival /Disease Free Interval

Palliation - Add Life to Years

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

Paradigm shift in Breast cancer treatmentParadigm shift in Breast cancer treatment

B. Fischer “ca breast is a systemic disease”

William Halsted “Local Radical Therapy”

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

Surgical ManagementSurgical Management

M R M

Total mastectomy with

Axillary Dissection

BCT - QUART

Quadantectomy

with

Axillary Dissection

with

Radiotherpy

RADIOTHERAPY IS A MUST

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%

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

SENTINEL Node BiopsyLYMPHAZURIN BLUE

DYE

Tc99 SULPHUR COLLOID

Accuracy 99%

Management of Mastectomy Specimen

Management of Mastectomy Specimen

HPE Grading

Margins

Ax Nodes – IM ?

Receptors

Her2/neu

DNA content

S - phase fraction

ESTROGEN RECEPTOR STATUS

Pg Receptor &

HER-2/neu

HER2/neu

Overexpression

Herceptin

The outer layer is called the basal layer and the inner layer is called the luminal layer.

Triple-negativeBreast cancers

Stage I & II Adjuvant therapyStage I & II Adjuvant therapy

Hormonal

Chemotherapy

Radiotherapy

Aromatase inhibitors

Herceptin

Biphosphonates

Adjuvant systemic therapyStage I & Stage II

Adjuvant systemic therapyStage I & Stage II

PREMENOPAUSAL POSTMENOPAUSAL

ER+ CHEMOTHERAPY/OVARIAN ABLATION/TAMOXIFEN

TAMOXIFEN +/- CHEMOTHERAPY

ER- CHEMOTHERAPY CHEMOTHERAPY

Cell cycle and cytotoxic opportunities

CELLDIFFERENTIATION

CELLLIFE CYCLE

TIME

CELLDIVISION

G2 PERIOD

(CHROMOSOME REPLICATION) S-PHASE

G1 PERIOD

Hormonal Managemrnt of Carcinoma Breast

Sir George Beatson

Oophorectomy

TAMOXIFENAROMATASE INHIBITORS

Hormonal Managemrnt of Carcinoma Breast

Sir George Beatson

Oophorectomy

TAMOXIFENAROMATASE INHIBITORS

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

Disruption of cadherin junctions

Focal contact/adhesion turnover

GPCR signalingcross-talk

RTK phosphorylation signal modulation and cross-talk

Cytoskeleton

ApoptosisProliferation

ba

SRC

If getting chemotherapy…If getting chemotherapy…

Radiation is usually withheld until after the systemic therapy is complete.

Followed with Hormonal therapy if indicated

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.

RT as Adjuvant

Radio therapy & BCT

RT as Adjuvant

Radio therapy & BCT

48% vs34%

Breast Reconstruction

BREAST RECONSTRUCTION

TRAM

&

LD

FLAPS

ONCO PLASTIC SURGERY

Management of Advanced Ca Breast

LABC & Systemic disease

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.