CARCINOMA

BREAST

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AN OVERVIEWAN OVERVIEWV

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Dr.B.SELVARAJ,MS;Mch;Dr.B.SELVARAJ,MS;Mch;

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•PEDIATRIC SURGEONV

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•PEDIATRIC SURGEON

•SVMCH&RC

•PONDICHERRY- 605102

OBJECTIVES

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•Etiopathogenesis

•Types &Clinical featuresV

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•Types &Clinical features

•Investigations

•Staging

•Treatment of EBC, LABC&ABC

ANATOMY

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ANATOMY

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ETIOPATHOGENESISIncidence of Sporadic, Familial, and Hereditary Breast Cancer

Sporadic breast cancer 65–75%

Familial breast cancer 20–30%

Hereditary breast cancer 5- 10%S

BRCA1 a 45%

BRCA2 35%

p53 a (Li-Fraumeni syndrome) 1%

STK11/LKB1a (Peutz-Jeghers syndrome) <1%

PTENa (Cowden disease) <1%

MSH2/MLH1a (Muir-Torre syndrome) <1%

ATMa (Ataxia-telangiectasia) <1%

Unknown 20%

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Risk Factors

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Major factors

Gender

Age

Previous breast cancer

Family history and genetic predisposition (BRCA 1 or 2 mutations)

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Intermediate factors

Alcohol and diet

Endocrine factors:

Early menarche

Late menopause

Hormone replacement therapy

Nulliparity

Irradiation

Benign proliferative breast disease (e.g. multiple papillomatosis)

Smoking & OCPs not a risk factor

TYPES

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Classification of Primary Breast Cancer

Noninvasive Epithelial Cancers Lobular carcinoma in situ (LCIS)

Ductal carcinoma in situ (DCIS)

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Invasive Epithelial Cancers (Percentage of Total) Invasive lobular carcinoma (10%-15%)

Invasive ductal carcinoma

Invasive ductal carcinoma, NOS (50%-70)

Tubular carcinoma (2%-3%)

Mucinous or colloid carcinoma (2%-3%)

Medullary carcinoma (5%)

Invasive cribriform carcinoma (1%-3%)

Invasive papillary carcinoma (1%-2%)

Adenoid cystic carcinoma (1%)

Metaplastic carcinoma (1%)

Clinical Features

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• Visible / Palpable Lump

• Hard Consistency

• Non Tender

• Paget’s Disease of the Nipple

• Skin

Tethering/dimpling/puckerin

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• Non Tender

• Low mobility

• Axillary Lymphnodes+

• Nipple Retraction

• Nipple Discharge

Tethering/dimpling/puckerin

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• Peau d’Orange

• Skin Ulceration / Fungation

Clinical Features

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The location of breast cancer is as follows:

Upper outer quadrant: 60%

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Upper outer quadrant: 60%

Central area : 12%

Lower outer quadrant: 10%

Upper inner quadrant: 12%

Lower inner quadrant: 6%

Clinical Features

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Clinical Features

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Peau d’ orange

Appearance

Clinical Features

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Skin dimpling and

puckering are inspectory

findings

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Tethering is due to

infiltration of Astley

cooper’s ligaments and is

confirmed by palpation

Clinical Features

SNipple retraction-

Recent, Unilateral,

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Recent, Unilateral,

circumferential

infiltration and fibrosis

of lactiferous ducts

Clinical Features

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Nipple discharge

suggestive of

malignancy if:

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1. Spontaneous

2. Unilateral

3. From single duct

4. Bloody discharge

5. Asso with mass

6. Age > 40 yrs

Skin Ulceration

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Paget’s Disease of Nipple

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�Eczema like condition

�Malignant cells in the V

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�Malignant cells in the

subdermal layer

�Red flat ulcer, nipple

erosion

Paget’s Disease of Nipple

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Paget’s Disease of

Nipple

Eczema of Breast

Unilateral Bilateral

Itching absent Itching present

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Absence of oozing Presence of oozing

Scales & Vesicles absent Scales & Vesicles present

Nipple destroyed Nipple intact

Underlying lump may be

present

No underlying lump present

Edges are distinct Edges are indistinct

No response to treatment Responds to treatment

Occurs at menopause( old

age)

Seen in lactating women(

young women)

INVESTIGATIONS

S“The choice of initial diagnostic evaluation after

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“The choice of initial diagnostic evaluation after

the detection of a breast lump should be

individualised for each patient according to the

age, perceived cancer risk and characteristics

of the lesion.”

INVESTIGATIONS

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INVESTIGATIONS

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• Radiological Investigations

• Ultrasonography• Mammography

• Pathological Investigations

• Staging

Investigations

• Xray Chest

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• Pathological Investigations

• Fine Needle Aspiration Cytology�FNAC

• Core Needle Biopsy� Trucut Biopsy

• Needle Localisation Biopsy• Stereotactic Biopsy• Open Biopsy� Incisional& Excisional

• Sentinel node Biopsy

• Xray Chest

• Abdominal

Ultrasound

• Radionucleide

Bone Scan

• CT Brain

Mammography

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• Irregular Margins

• Ill-defined margins

• AsymmetryV

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• Asymmetry

• Clustered pleomorphic

microcalcification

• Architectural distortion

• Stellate or spiculated

appearance

Mammography

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Ultrasonography

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• High frequency 7MHz probe is used although 10 to 13MHz preferable

• Differentiate solid and cystic lesions

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cystic lesions

• Malignant appearing masses

1.Irregular margins

2.Hypoechoic

3.Posterior acoustic shadow

4.Vertical growth appearance (TALLER than wide)

FNAC

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• 1.5 inch 22 gauge needle attached to a 10 ml syringe is used

• With or without image guidance

• FNAC-DISADVANTAGESV

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• FNAC-DISADVANTAGES

1. FALSE NEGATIVE rate high

2. Inadequate specimen

3.Requires skilled cytopathologist

4. Cannot differentiate in situ vsinvasive lesions

Trucut Needle Biopsy

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Core needle Biopsy• Done using a 14 gauge needle or Tru

cut needle

• ADVANTAGES

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• ADVANTAGES

1. Lower FALSE negative rates

2. Doesn't need specially trained

cytopathologist

3. Adequate samples are obtained

4.Can differentiate in situ vs invasive

lesions

5.Can confirm-ER/PR/Her 2 neu status

Investigations for Nonpalpable

Lumps

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Image guided biopsies

1.USG guided FNAC or core

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1.USG guided FNAC or core needle biopsy(if mass is visualised)

2. Needle localising biopsy

3. STEREOTACTIC needle biopsy

(when no mass present but micro calcifications seen mammographically)

Sentinel Node Biopsy

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•• LYMPHAZURIN LYMPHAZURIN

BLUE DYEBLUE DYE

•• Tc99 SULPHUR Tc99 SULPHUR

COLLOIDCOLLOID

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COLLOIDCOLLOID

•• Accuracy 99%Accuracy 99%

Sentinel Node Biopsy

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INDICATIONS CONTRAINDICATIONS

• High-risk IN SITU

cancer, non-palpable

breast cancer

• Altered drainage of breast.eg-

Augmentation surgery

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breast cancer

• T1 or T2 carcinoma

and especially good

prognosis tumors

(mucinous, papillary

and adenoid cystic)

• Recent

mammoplasty,pregnancy

• Allergy to dye or radiocolloid

• Inflammatory Ca

• Axillary mets

Other Investigations

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1.CXR-PA VIEW

2.CT CHEST

3.USG – ABDOMEN AND PELVIS

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3.USG – ABDOMEN AND PELVIS

4.SKELETAL SURVEY/ Tc99 BONE SCAN

5.MRI BREAST- Voluminous breast/ Implant

rupture

6.PET SCAN- Follow up to detect residual disease

7.Tumor Marker- CA- 15/3

AJCC Staging

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T (Primary Tumor)

Tis Carcinoma in situ (lobular or ductal)

T1 Tumor <2 cm

T2 Tumor >2 cm, <5 cm

T3 Tumor >5 cmM (Metastasis)

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T3 Tumor >5 cm

T4 Tumor any size with extension to the

chest wall or skin

N (Nodes)

N0 No regional node involvement

N1 Metastasis to 1-3 axillary nodes

N2 Metastasis to 4-9 axillary nodes

N3 Metastasis to >10 axillary nodes

M (Metastasis)

M0 No distant

metastasis

M1 Distant metastasis

AJCC Staging

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• Stage 1 and stage 2 –EBC

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• Stage 3 – LABC

▪ 3a- T3, N 1,2,▪ 3b- T4, ANY N▪ 3c- N3, ANY T

• Stage 4- ABC

Management-Multimodality

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• Surgery

• Curative

• Palliative

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• Radiotherapy

• Chest Wall

• Axilla

• Supraclavicular

• Chemotherapy

• Hormonal Therapy

Management

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•Stage 1 & 2

• Breast conservation

•Stage 3

• MRM+Adjuvant RT+

•Stage 4

•Toilet Mastectomy

EBC LABC ABC

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• Breast conservation

treatment

� Lumpectomy

� Wide local excision

� Quadrantectomy

� Axillary dissection

� Radiotherapy

•Modified radical

mastectomy

• MRM+Adjuvant RT+

Adjuvant CT +/- HT

• Neoadjuvant CT+MRM+

Adjuvant RT &CT+/- HT

•Toilet Mastectomy

•Adjuvant RT & CT +/-

HT

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Breast Conservation Treatment

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Management- LABC

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Classification of LABC

•LABC Operable at Presentation

•T3, N1, M0V

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•T3, N1, M0

•LABC Inoperable at Presentation

•T4, Any N, M0

•Any T, N2 or N3, M0

•Inflammatory Carcinoma of Breast

•T4d, N0, M0

Management- LABC

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Treatment of Operable LABC

� MRM → Adjuvant Radiotherapy (RT) & Adjuvant

Systemic Chemotherapy (CT) +/- Hormone Therapy V

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Systemic Chemotherapy (CT) +/- Hormone Therapy

(HT)

� Neoadjuvant CT→ To attempt to Down-Stage

lesions for Breast Conservation Surgery

� Tumor Responding → BCS → CT,RT +/- HT

� Non-responders → MRM → CT with RT +/-

HT

Management- LABC

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Treatment of Inoperable LABC

Aim of Treatment: To make the disease operable and achieve

loco – regional control, hence improve patients quality of life

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loco – regional control, hence improve patients quality of life

Neoadjuvant CT → MRM → CT & RT +/- HT

Advantages of Neoadjuvant CT

To make the tumor operable

To assess tumor response to CT

Management- MRM

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Prognostic Factors

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1.Axillary nodal status( most important)

2.Tumour size

3.ER/PR Status – Both positive- good prognosis

4.Histological grade of tumour

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4.Histological grade of tumour

5.Her 2neu overexpression – aggressive malignancy-

poor prognosis

6.Proliferating rate

1.DNA flow cytometry – aneuploid – poor

prognosis

2.S phase fraction – low S phase – good prognosis

Prognostic Factors

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Stage 1 – 90%

5 yr survival – Ca Breast

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Stage 1 – 90%

Stage 2 – 70%

Stage 3 – 40 %

Stage 4 – 20 %

Adjuvant Chemotherapy

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To deal with occult metastasis

Always use combination chemotherapy

More effective in pre-menopausal

CT + HT > CT / HT alone

Drugs used:

Schedule used commonly:

CAF q21d x 6cycles

Cyclophosphamide: 500mg/m2 D1

5 – FU: 500mg/m2 D1 & D8

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Drugs used:

Cyclophosphamide

Methotrexate

5 – FU

Anthracyclines: Doxorubicin,

Epirubicin

Taxanes: Paclitaxel, Docitaxel

5 – FU: 500mg/m2 D1 & D8

Doxorubicin: 50mg/m2 D1

Regimen of choice: TAC

Good efficacy irrespective of

ER/PR/HER-2 neu status

Neoadjuvant Chemotherapy

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CT given before Local Control of disease

It does not provide any survival advantage

Helps decide response of tumor to CT

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Helps decide response of tumor to CT

Indications:

1.To downstage Operable LABC for BCT

2.To downstage Inoperable LABC for operability

3.Inflammatory Breast Cancer

4.In EBC, to improve cosmetic appeal after BCS, for large

tumor in small breast

Neoadjuvant Chemotherapy

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�Usually 2 – 4 cycles are given till maximum shrinkage

is achieved

�Choice of drugs are the same as for Adjuvant CT –V

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�Choice of drugs are the same as for Adjuvant CT –

CAF / TAC

�If tumor is resistant then non cross resistant drugs can

be used as second line CT

Hormone Therapy

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�ER+/PR+ → 80% chance of

favorably response to HT

�Most commonly used agent

→ Tamoxifen

Dose: 20mg/day, Oral

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�All (pre/post menopausal)

patients with ER/PR+ LABC

should undergo HT for 5yrs.

�Can be given in combination

with CT

Dose: 20mg/day, Oral

Side effects: Hot flushes,

sexual dysfunction,

endometrial cancer,

thromboembolism

Hot flushes →

Venlafaxine, Paroxetine

Hormone Therapy

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ClassClass AgentsAgents

Selective estrogen receptor Selective estrogen receptor

modulators (SERMS)modulators (SERMS)TamoxifenTamoxifen, Raloxifene, , Raloxifene,

ToremifeneToremifene

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AromataseAromatase inhibitorsinhibitors AnastrozoleAnastrozole, Letrozole, , Letrozole,

ExemestaneExemestane

Pure antiestrogensPure antiestrogens FulvestrantFulvestrant

LHRH agonistsLHRH agonists Goserelin, Leuprolide Goserelin, Leuprolide

Progestational agentsProgestational agents MegestrolMegestrol

AndrogensAndrogens FluoxymesteroneFluoxymesterone

HighHigh--dose estrogensdose estrogens DiethylstilbestrolDiethylstilbestrol

Hormone Therapy

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Trastuzumab or Herceptin

�Monoclonal antibody that targets the HER-2 neu

oncogene

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oncogene

�Her 2 neu codes for a growth factor that is overexpressed

in 25% to 30% of breast cancers

�Her 2 neu over-expression indicates aggressive nature of

malignancy.

�Trastuzumab may be used for Her 2 neu positive

tumours in adjuvant or neo adjuvant setting

Radiotherapy

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Indications for PMRT:

4 Positive axillary nodesV

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1. >4 Positive axillary nodes

2. Tumour size > 5 cm

3. Positive surgical margins

4. As a part of LABC PROTOCOL

Followup

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� Monthly self examination of the breast

� Regular physical examination following mastectomy is necessary

� Every 4 months for years 1 and 2,

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� Every 4 months for years 1 and 2,

� Every 6 months for years 3 through 5,

� Every 12 months thereafter

� Contralateral mammogram yearly

� Routine bone scans, skeletal surveys, CT of abdomen and brain- Not

necessary, Yield is low