Breast Carcinoma

BREASTCARCINOMA

Presented byStudents of

Surgery Unit II

• Breast cancer is the most common cancer among Indian women and 2nd leading cause of cancer deaths in women.

• Though it is more common in the western countries the incidence of breast cancer is increasing due to urbanization, adoption of western lifestyle.

• Yet there is more reason for optimism than ever before as in the last 30 years doctors have made great strides in early diagnosis and treatment and reducing breast cancer death.

INTRODUCTION

BREAST CARCINOMA : RISK FACTORS,

RISK ASSESSMENT, ANDRISK PREVENTION

BySAYAN MAHARATNA

Roll No.- 77

RISK FACTORSOF

BREAST CARCINOMA

• Age• Early menarche and late menopause• Hormonal factors• Parity• Diet and obesity• Family history• Prior breast biopsy• Socio economic status

RISK FACTORS

Factors Relative riskGeography Varies in different

areasAge Increases after age

30Family history• First degree relative with

breast caPremenopausalPremenopausal and bilateral PostmenopausalPostmenopausal and bilateral

1.2-3.03.1

8.5-9.01.5

4.0-5.4

RELATIVE RISK OFDIFFERENT FACTORS

(contd.)

Factors Relative RiskMenstrual history

Age at menarche <12 yearsAge at menopause >55 years

1.31.5-2.0

Pregnancy1st live birth from ages 25-29 years1st live birth after age 30 years1st live birth after age 35 yearsNulliparous

1.51.9

2.0-3.03.0

Benign breast diseaseProliferative disease without atypiaProliferative disease with atypical

hyperplasiaLobular carcinoma in situ

1.6>2.0

6.9-12.0

RISK ASSESSMENTOF

BREAST CARCINOMA

RISK ASSESSMENT MODELS

GAIL MODEL CLAUS MODELData derived from

Breast Cancer Detection demonstration Project Study

Cancer and Steroid Hormone Study

Family history characteristic

FDR with breast cancer •FDR or SDR with breast cancer•Age of onset in relatives

Other characteristic

• Current age• Age at menarche• Age at first live birth• Number of breast

biopsies• Race

Current age

(contd.)

GAIL MODEL CLAUS MODELStrength Incorporates –

Risk factors other than family history

Incorporates –•Paternal and maternal history•Age of onset•Familial history of ovarian carcinoma

Limitations

•Underestimates risk in hereditary families•Number of breast biopsies without atypical hyperplasia may cause inflated risk estimates

Does not incorporate –•Paternal family history of breast cancer or family history of ovarian cancer•Age at onset of breast cancer in relatives•All known risk factors for breast cancer

•May underestimates risk in hereditary families•May not be applicable to all combination of affected relatives

(contd.)

GAIL MODEL CLAUS MODELBest application

•For individuals with no family history of breast cancer or one FDR with breast cancer, aged 50 or above.•For determining eligibility of chemoprevention studies.

For individuals with no more than two FDR or SDRs with breast cancer.

OTHER RISK ASSESSMENT MODELS:• BRCAPRO• Tyrer Cuzik’s Model

WEBSITE TO CALCULATE RELATIVE RISK

RISK PREVENTIONOF

BREAST CARCINOMA

BREAST CANCER SCREENING

RISK REDUCING SURGERY

CHEMOPREVENTION

RISK PREVENTION

BREAST CANCER SCREENING MAMMOGRAPHY

• Routine use of mammography in women aged 50 years or above has been reported to reduce mortality from breast cancer by 25%.• Recommendation- Baseline mammography at age of 35 and

from 40 years annually. MRI

Approved for screening of young high risk patients who have-• Strong family history• BRCA mutation carriers• With a history of Li-Fraumeni syndrome and Cowden syndrome

USGIt can be used in pregnant women.

RISK PREVENTION

CHEMOPREVENTION

SERM Therapy by Tamoxifen, Raloxifen• Should be given if relative risk >1.66• After a mean follow up period of 4 years the incidence of breast

cancer was reduced by 49%• Optimal duration of treatment is 5 years. (NSABP-1)

Aromatase inhibitors- Exemestane, Anastrozol• More suitable for reducing the incidence of contralateral breast

cancer in post menopausal women

RISK PREVENTION

RISK REDUCING SURGERY

Prophylactic mastectomy• Reduces risk >90%• For women with an estimated life time risk of 40%,

prophylactic mastectomy adds 3 years of life where as for women with an estimated life time risk of 85% prophylactic mastectomy adds >5 years

Salpingo-oophorectomy• Reduces the risk of both ovarian and breast carcinoma in

BRCA mutation carriers (hereditary breast and ovarian cancer syndrome).

RISK PREVENTION

BREAST CARCINOMA:CLINICAL ASSESSMENT,INVESTIGATIONS AND

STAGINGBy

SOAHAM TARAPHDARRoll No.- 83

CLINICAL ASSESSMENTOF

BREAST CARCINOMA

CLINICAL ASSESSMENT

Clinical assessment

History Clinical Examination

General Survey Local

Examination of Breast

Systemic Examination

• Inspection• Palpation

MAJOR POINTS TO BE NOTED:• Age• Lump in breast: Mode of onset, duration, rate of

growth• Pain• Breast or axillary changes• Nipple: Retraction, Discharge• Past history: H/O irradiation, cancers• Personal history: Marital status, menstrual history• Family history

HISTORY TAKING

POSITIONS:• Arms by her side• Arms straight up in

the air• Hands on her hips

(with and without pectoral muscle contraction)

• Arms extended forward in a sitting position leaning forward

• Semi recumbent position with head raised by 45°

INSPECTION

MAJOR POINTS TO BE NOTED:• Breast: Symmetry, Size, Shape, Edema (peau d’

orange), Any visible lump or fungation• Skin: Retraction, Erythema, Ulceration• Nipple: Retraction, Erythema, Ulceration, Discharge

INSPECTION

• In sitting, semi-recumbent and recumbent position• Examination of all quadrants of the breast, along with the

axillary tail• Done with the pads of the middle 3 fingers; avoid

grasping and pinching motion

PALPATION OF BREAST

POINTS TO BE NOTED IN CASE OF BREAST LUMP:• Temperature• Tenderness• Number• Situation• Size • Shape• Surface• Consistency• Margin• Mobility or fixity of lump

Fixity to skin, breast tissue, pectoral muscle and fascia, chest wall

PALPATION OF BREAST

• Assessment of axillary lymphadenopathy

• Patient’s arm is supported on the non examining arm of examiner to maintain relaxation

• Examination with pads of middle 3 fingers in a circular motion

PALPATION OF AXILLA

INVESTIGATIONOF

BREAST CARCINOMA

TO CONFIRM THE DIAGNOSIS: Imaging• Mammography• USG• MRI

Biopsy• FNAC• Trucut biopsy

INVESTIGATIONS

PROCEDURE• Soft tissue radiographs are taken by placing the

breast in direct contact with an ultrasensitive film (selenium coated plate) and exposing it to low-voltage, high-amperage X-rays.

• Radiation dose is 0.1 cGy.• 2 views – (i) Mediolateral oblique and (ii)

Craniocaudal

INDICATIONS• Screening: Asymptomatic women of more than 40

years• Diagnostic: Women with pain in the breast, mass,

discharge, family history of breast cancer

MAMMOGRAPY

FINDINGS Benign: Round, punctate,

popcorn like lesions Malignant:• Solid mass with or without

stellate features• Asymmetric thickening of

breast tissue• Clustered microcalcifications• Tentaculation• Distortion of archtiectural

pattern of breast

MAMMOGRAPHY

MAMMOGRAPHY

Score

Assessment Follow up

0 Incomplete assessment Needs additional imaging1 Negative Continue regular screening (>40

yrs.)2 Benign findings Same as above3 Probably benign Follow up study after 6 month

4 Suspicious of carcinoma Core biopsy may be required5 Highly suggestive of

carcinomaCore biopsy is must

6 Known biopsy proven carcinoma

Biopsy confirms presence of cancer before treatment begins

BI-RADS scoring

ADVANTAGES• Non-invasive procedure• Minimum hazards of radiation

DISADVANTAGES• 5% false positive cases

MAMMOGRAPHY

• Particularly useful in young women with dense breasts in whom mammograpy is difficult to interpret

• Can distinguish between solid and cystic lesions

• Can be used to localise impalpable areas of breast pathology

• USG guided aspiration of breast may be done

• Cannot detect lesion less than 1mm in diameter

ULTRASONOGRAPHY (USG)

• Can be useful to distinguish scar from recurrence in women who have had previous breast conservation therapy for cancer

• Used in assessment of multifocality and multicentricity of lobular cancer

• Can be used to assess the extent of DCIS

• Best imaging modality for the breasts of women with implants

MRI

• Material is aspirated and collected on slide with 23G needle, smear is made, stained and examined

• More than 95% accuracy• False negative 15%• Invasiveness of cancer cannot

be determined

FNAC

FNAC Scoring

Co No epithelial cells

C1 Scanty epithelial cells , benign

C2 Benign cells

C3 Atypical cells

C4 Suspicious cells

C5 Malignant cells

• Also called Core cut biopsy or Vacuum-assisted biopsy

• Lesion specimen is obtained with 11G needle after proper antiseptic dressing and local anesthesia

• Histological diagnosis of invasive or non invasive carcinoma may be made

• Tumour grade and any lymphovascular invasion may be assessed

• ER/PR and Her2-neu status may also be assessed

TRUCUT BIOPSY

OTHER INVESTIGATIONS

TO STAGE THE DISEASE – METASTATIC WORK UP• CT scan chest• X-ray• Whole body bone scan• Upper abdominal USG with LFT• Sentinel node biopsy

TO KNOW THE GENERAL CONDITION• Complete haemogram with ESR• Serum albumin, sugar, urea, creatinine• ECG,Echo and Pulmonary function test for elder patients

TRIPLE ASSESSMENT

STAGINGOF

BREAST CARCINOMA

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 (Paget’s) Paget’s 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’s disease are categorized based on the size and characteristics of the parenchymal disease, although the presence of Paget’s disease should still be noted

TNM STAGING

PRIMARY TUMOUR (T)

T1 Tumor ≤20 mm in greatest dimension T1mi Tumor ≤1 mm in greatest dimension T1a Tumor >1 mm but ≤5 mm in greatest dimension T1b Tumor >5 mm but ≤10 mm in greatest dimension T1c Tumor >10 mm but ≤20 mm in greatest dimensionT2 Tumor >20 mm but ≤5 cm in greatest dimensionT3 Tumor >50 mm in greatest dimension

TNM STAGING

PRIMARY TUMOUR (T)

T4 Tumor of any size with direct extension to the chest wall and/or to the skin (ulceration or skin nodules)

T4a Extension to chest wall, not including only pectoralis muscle adherence/invasion

T4b Ulceration and/or ipsilateral satellite nodules and/or edema (including peaud’orange) of the skin, which do not meet the criteria for inflammatory carcinoma

T4c Both T4a and T4b T4d Inflammatory carcinoma

TNM STAGING

PRIMARY TUMOUR (T)

NX Regional lymph nodes cannot be assessed (e.g., previously removed)

N0 No regional lymph node metastasesN1 Metastases 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 metastases

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

TNM STAGING

REGIONAL LYMPH NODES – CLINICAL(N)

N3 Metastasis in ipsilateral infraclavicular (level III axillary) lymph node(s) with or without level I, II axillary lymph node involvement; or in clinically detected ipsilateral internal mammary lymph node(s) with clinically evident level I, II axillary lymph node metastases; or metastases 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 nodes(s)

and axillary lymph node(s) N3c Metastasis in ipsilateral supraclavicular lymph node(s)

TNM STAGING

REGIONAL LYMPH NODES – CLINICAL(N)

M0 No clinical or radiographic evidence of distant metastases

cM0(i+) No clinical or radiographic evidence of distant metastases, but deposits of molecularly or microscopically detected tumor cells in circulating blood, bone marrow, or other nonregional nodal tissue that are no larger than 0.2 mm in a patient without symptoms or signs of metastases

M1 Distant detectable metastases as determined by classic clinical and radiographic means and/or histologically proven larger than 0.2 mm

TNM STAGING

DISTANT METASTASIS (M)

Stage 0 Tis N0 M0

Stage IA T1 N0 M0

Stage IB T0 N1mi M0

T1 N1mi M0

Stage IIA

T0 N1 M0

T1 N1 M0

T2 N0 M0

Stage IIB

T2 N1 M0

T3 N0 M0

TNM STAGING

Stage IIIA T0 N2 M0

T1 N2 M0

T2 N2 M0

T3 N1 M0

T3 N2 M0

Stage IIIB T4 N0 M0

T4 N1 M0

T4 N2 M0

Stage IIIC Any T

N3 M0

Stage IV Any T

Any N

M1

TNM STAGE GROUPINGS

BREAST CARCINOMA:PATHOLOGICAL CLASSIFICATION

ByASIF RAHAMAN

Roll No.- 86

Breast Carcinoma

Carcinoma in situ Invasive Carcinoma

1.Ductal Carcinoma in situ

2. Lobular Carcinoma in situ

1. Paget’s disease of the nipple

2. Invasive ductal carcinoma

3. Medullary carcinoma4. Mucinous (colloid)

carcinoma5. Papillary carcinoma6. Tubular carcinoma7. Invasive lobular

carcinoma8. Rare cancers (adenoid

cystic, squamous cell, apocrine )

• Cancer cells are in situ or invasive depending on whether or not they invade through the basement membrane.

• Broders’s original description of in situ breast

cancer stressed the absence of invasion of cells into the surrounding stroma and their confinement within natural ductal and alveolar boundaries.

CARCINOMA IN SITU

• Although DCIS is predominantly seen in the female breast, it accounts for 5% of male breast cancers.

• Histologically, DCIS is characterized by a proliferation of the epithelium that lines the minor ducts, resulting in papillary growths within the duct lumina.

DUCTAL CARCINOMA IN SITU (DCIS)

(contd.)

• The papillary growths (papillary growth pattern) eventually coalesce and fill the duct lumina so that only scattered, rounded spaces remain between the clumps of atypical cancer cells, which show hyperchromasia and loss of polarity (cribriform growth pattern).

• Eventually pleomorphic cancer cells with frequent mitotic figures obliterate the lumina and distend the ducts (solid growth pattern).

TYPES OF DCIS

• Solid type, Ductal Carcinoma in situ: The tumour cells completely fill the involved ducts.

• Cribriform type, Ductal Carcinoma in situ: The tumour cells do not completely fill the ducts. The pattern has little holes and slits, similar to a sieve.

• Papillary and micropapillary types, Ductal Carcinoma in situ:These two types have fern-like projections of cells into the centre of the duct. The micropapillary type projections are smaller than those seen with the papillary type. (contd.)

• Comedo type Ductal Carcinoma in situ:

It tends to be slightly more aggressive than the other forms of DCIS.

Appearance under the microscope: The individual cells look more abnormal The centre of the duct is plugged up with dead

cellular debris, known as necrosis.

Also seen very often in mammograms the areas of necrosis are microcalcifications – small abnormal calcium deposits in the areas of necrosis.

LOBULAR CARCINOMA IN SITU (LCIS)

• Originates from the terminal duct lobular units and develops only in the female breast.

• Characterized by distension and distortion of the terminal duct lobular units by cells

• Characterized by dyscohesive cells lacking E-cadherin adhesion protein.

LOBULAR CARCINOMA IN SITU (LCIS)

• Malignant proliferation of cells in lobules with no invasion of the basement membrane.

• Does not produce a mass or calcifications; usually discovered incidentally on biopsy.

• Often multifocal and bilateral.

PAGET’S DISEASE OF THE NIPPLE

• Frequently presents as a chronic, eczematous eruption of the nipple, which may be subtle but may progress to an ulcerated, weeping lesion.

• Usually is associated with extensive DCIS, may be associated with an invasive cancer.

PAGET’S DISEASE OF THE NIPPLE

• Nipple biopsy specimen shows a population of cells that are identical to the underlying DCIS cells (pagetoid features or pagetoid change).

• Pathognomonic of this cancer is the presence of large, pale, vacuolated cells (Paget cells) in the rete pegs of the epithelium.

INVASIVE DUCTAL CARCINOMA

• Occurs most frequently in perimenopausal or postmenopausal women in the fifth to sixth decades of life.

• Presents as a solitary, firm mass with poorly defined margins.

• Broad spectrum of histologic types with variable cellular and nuclear grades.

INVASIVE DUCTAL CARCINOMA

• Cut surfaces show a central stellate configuration with chalky white or yellow streaks extending into surrounding breast tissues.

MEDULLARY CARCINOMA

• 4% of all invasive breast cancers.

• Frequent phenotype of BRCA1 hereditary breast cancer.

• Gross characteristics: Soft and haemorrhagic A rapid increase in size

may occur secondary to necrosis and haemorrhage.

MEDULLARY CARCINOMA• Microscopic

characteristics:

Dense lymphoreticular infiltrate composed predominantly of lymphocytes and plasma cells

Large pleomorphic nuclei that are poorly differentiated and show active mitosis

Sheet-like growth pattern with minimal or absent ductal or alveolar differentiation

MUCINOUS (COLLOID) CARCINOMA


• Typically presents in the elderly population as a bulky tumour.

• Cut surface is glistening and gelatinous.

• Fibrosis is variable, and when abundant, imparts a firm consistency to the cancer.

MUCINOUS CARCINOMA

• Microscopically defined by extracellular pools of mucin surrounding aggregates of low-grade cancer cells.

• Generally presents in the seventh decade of life.

• Occurs in a disproportionate number of non-white women.

• Typically small, rarely attain a size of 3 cm in diameter.

• Defined by papillae with fibrovascular stalks and multilayered epithelium.

PAPILLARY CARCINOMA


• Diagnosed in the perimenopausal or early menopausal periods.

• Under low-power magnification, a haphazard array of small, randomly arranged tubular elements are seen.

• Distant metastases are rare.

• Long-term survival approaches 100%.

TUBULAR CARCINOMA

• 10% of breast cancers.

• Presentation: Varies from clinically inapparent carcinomas to those that replace the entire breast with a poorly defined mass.

• Frequently multifocal, multicentric, and bilateral.

LOBULAR CARCINOMA

LOBULAR CARCINOMA

• Histopathological features:

Small cells with rounded nuclei, inconspicuous nucleoli, and scant cytoplasm.

Special stains may confirm the presence of intracytoplasmic mucin, which may displace the nucleus (signet-ring cell carcinoma).

BREAST CARCINOMA:MOLECULAR

CLASSIFICATION,BIOMARKERS AND

PROGNOSTIC FACTORSBy

MAYUKH MUKHERJEERoll No.- 84

MOLECULAR CLASSIFICATION OF

BREAST CARCINOMA

Subtype These tumours tend to be(Characteristics)

Prevalence (approximate

)

Luminal A

• ER-positive and/or PR-positive• HER2-negative• Low Ki67

40-55%

Luminal B

• ER-positive and/or PR-positive• HER2-positive (or HER2-negative with high Ki67)

15-20%

Basal-like(Triple –ve)

• ER-negative• PR-negative• HER2-negative

13-25%

HER2 type

• ER-negative• PR-negative• HER2-positive

7-12%

Normal breast-like

• ER-positive• HER2-negative

6-10%

• Express ER• Most common• Posses a higher ER and oestrogen associated gene

ESR1, GATA3, and FOXA1• Do not express HER-2/neu• Ki-67 proliferation index is low• Luminal A tumours are associated with better prognosis

LUMINAL A

Association of osteopontin, cyclooxygenase 2, oestrogen receptor, progesterone receptor & human epidermal growth factor receptor 2

LUMINAL A

• Express ER• Variable HER-2/neu expression• Increased frequency of TP53 mutations• Ki-67 proliferation index is high• Luminal B tumours are associated with worse prognosis

than Luminal A

LUMINAL B

LUMINAL BAssociation of osteopontin, cyclooxygenase 2, oestrogen receptor,

progesterone receptor & human epidermal growth factor receptor 2

• Hormone receptor (ER and PR) and HER-2/neu receptor negative

• Expression of genes associated with myoepithelial cells: KRT5 (keratin 5), KRT17 (keratin 17), CNN1 (calponin 1), CAV1 (caveolin) and LAMB1 (laminin)

• Aggressive with a poorer disease free and overall survival than other breast cancer subtypes.

BASAL LIKE (TRIPLE NEGATIVE)SUBTYPE

BASAL LIKE (TRIPLE NEGATIVE)SUBTYPE


• Increased expression of genes located in the same region of chromosome 17q: human epidermal growth receptor factor 2, and growth factor receptor bound protein 7

• Associated with high histological grade, low expression of ER and PR

• Poor clinical outcome.

HER-2/NEU OVER EXPRESSINGSUBTYPE

HER-2/NEU OVER EXPRESSINGSUBTYPE


BIOMARKERS INBREAST CARCINOMA

TYPES OF BIOMARKERS

Endpoint biomarkersUsed as endpoints in short term chemoprophylaxis trials.

Prognostic biomarkersFor info regarding cancer outcome irrespective of therapy.

Predictive biomarkersFor info regarding response to therapy.

Risk factor biomarkers:• Familial clustering and inherited germ line abnormality• Proliferative breast disease with atypia• Mammographic densities

Exposure biomarkers: e.g. DNA adducts

Surrogate endpoint biomarkers:Markers of biologic alterations in tissues that occur between cancer initiation and development

ENDPOINT BIOMARKERS

a.Indices of proliferation• PNCA (Proliferating cell nuclear antigen)• Ki 67

b.Indices of apoptosis and apoptosis modulators• bcl-2• bax:bcl-2 ratio

c. Indices of angiogenesis• VEGF• AI (Angiogenesis index)

PROGNOSTIC AND PREDICTIVEBIOMARKERS

(contd.)

d.Growth factor and growth factor receptor• HER-2/neu (Human epidermal growth factor receptor 2)• EGFr (Epidermal growth factor receptor)• Transforming growth factor• PDGF (Platelet derived growth factor)• IDGF (Insulin derived growth factor)

e.Steroid hormone receptor pathway• Estrogen receptor

ER alpha ER beta

• Progesterone receptor PR alpha PR beta (contd.)

f. Cell cycles, cyclines, cell dependent kinase S

g.Proteasome

h.COX-2 enzyme

i. PPARs (Peroxisome proliferator activated receptors)

j. Tumour suppressor genes: p53

k.mTOR (Mammalian target of rapamycin) signalling

pathway

PROGNOSTIC FACTORSOF

BREAST CARCINOMA

Tumour Factors Host Factors

Nodal Status Age

Tumour size Menopausal status

Histologic/Nuclear grade Family history

Lymphatic/Vascular invasion Previous breast cancer

Pathologic stage Immunosuppresion

Hormone receptor status Nutrition

DNA content (Ploidy, S phase fraction) Prior chemotherapy

Extent of intraductal component Prior radiation therapy

HER-2/ neu expression

A FEW POINTS ABOUTPROGNOSTIC FACTORS

• Spread to the axillary nodes is the most important prognostic indicator.

Lymph node as prognostic factor Number of nodes: >2 carries poor prognosis Location of nodes Capsular invasion Size of nodes: >2.5cm ha poor prognosis More than 4 nodes/level III (apical nodes)

involvement has worst prognosis(contd.)

• Younger age has worse prognosis• CA male breast has worse prognosis than CA female

breast• Stage 1 & 2 of carcinoma of breast has better

prognosis than stage 3 & 4• ER +ve & PR +ve tumours have better prognosis• HER-2/neu +ve tumours have poor prognosis• p53 tumour suppressor gene shows bad prognosis• Inflammatory carcinoma has worst prognosis• Tumour size less than 1cm has better prognosis

BREAST CARCINOMA:TREATMENT OPTIONS

AND SURGERY

BySHRONA BANDOPADHYAY

Roll No.- 82

SURGERY

CHEMOTHERAPY

RADIOTHERAPY

HORMONAL THERAPY

TREATMENT MODALITIES

CHOICE OF TREATMENT

ACCORDING TO STAGING WITH EMPHASIS ON

SURGICAL METHODS

IN SITU (STAGE 0)

LOBULAR CARCINOMA IN SITU (LCIS):

• Observation or• Chemoprevention or• B/L Total Mastectomy

DUCTAL CARCINOMA IN SITU (DCIS):

• Limited disease : Lumpectomy with radiation.

• Extensive disease : Modified radical mastectomy (MRM).

Breast Conservation Surgery (BCS): Lumpectomy with Radiation.

Modified Radical Mastectomy (MRM).

Whether BCS or MRM assessment of Lymph node status is done. Clinically negative axillary LN status has to be detected by sentinel LN biopsy.

When clinically palpable or sentinel LN biopsy is positive then axillary clearance is to be performed by dissecting the level I and II LN.

(contd.)

EARLY INVASIVE BREAST CARCINOMA (STAGE I, IIA, OR IIB)

Unless contraindicated, here Lumpectomy with Radiation therapy is preferred over MRM because :

• Equivalent in terms of oncologic safety

• Better quality of life & aesthetics post surgically.

• Preservation of breast shape and skin as well as sensation.

ADVANCED LOCAL-REGIONAL BREAST CARCINOMA (STAGE IIIA OR IIIB)

Neoadjuvant Chemotherapy

Reassessment of stage

MRM with axillary LN level I, II, III dissection

Adjuvant Radiation Therapy

Systemic Chemotherapy

Hormonal Therapy

Radiation Therapy

Palliative Surgery

DISTANT METASTASES (STAGE IV)

BREAST CONSERVATION

SURGERY

BREAST CONSERVATION SURGERY (BCS)

Principle: Breast tissue, nipple-areolar complex and skin are preserved. BCS is always associated with Radiation Therapy.

QUART: Quadrantectomy + axillary LN clearance (Level I, II, III) + post operative radiation therapy.

Lumpectomy: Lump with 1cm normal surrounding breast tissue is excised.

INDICATIONS: • Early breast carcinoma with tumour size < 4cm.• Radiation is not contraindicated.• Facility of radiation is present.

CONTRAINDICATIONS: • Multicentric tumour.• History of previous breast irradiation.• Pregnancy.• Persistent positive margins after reasonable surgical

attempts.• Collagen vascular disease.

LUMPECTOMY

DISADVANTAGES :

• Higher rate of local recurrence, more common in younger women and tumours with high grades.

• Needs radiotherapy after surgery.

LUMPECTOMY

MASTECTOMY

TYPES OF MASTECTOMY

Simple or total mastectomy

Removal of breast tissue, nipple-areola complex, skin.

Extended simple mastectomy

Removal of breast tissue, nipple-areola complex, skin & level I axillary nodes.

Modified radical mastectomy

Removal of breast tissue, nipple-areola complex, skin & level I, II axillary LNs.

Halstead’s radical mastectomy

Removal of breast tissue, nipple-areola complex, skin, pectoralis major & minor &level I, II, III axillary LNs.

Extended radical mastectomy

Radical mastectomy + removal of internal mammary LNs.

Super radical mastectomy

Radical mastectomy + removal of internal mammary LNs, mediastinal & supraclavicular LNs.

Most acceptable and most widely practised surgery.

Advantages over radical mastectomy:• Good postoperative cosmetic appearance• Maintain motor activity in the arm• Low rate of postoperative arm oedema• Easy postoperative breast reconstruction

MODIFIED RADICAL MASTECTOMY

TYPES:It is of 3 types:1.Patey’s Modified Radical Mastectomy: Pectoralis

major muscle is preserved and Pectoralis minor removed.

2. Scanlon’s Modified Radical Mastectomy: Pectoralis minor muscle is divided but not removed.

3.Auchincloss’ Modified Radical Mastectomy: Pectoralis minor is retraced but not divided.

Auchincloss’ Modified Radical Mastectomy is widely practiced nowadays.


INDICATIONS:• Large tumour size > 5cm.• Multicentric tumour.• Surgical lines after lumpectomy are not free of

tumour.• Poorly differentiated tumour.


INCISIONTransverse elliptical incisions, including the nipple areola complex and skin overlying the tumour together with skin margins that lie 1-2 cm from the cephalic and caudal extents of the tumour.


Anatomical boundaries of MRM:• Lateral: Anterior margin of latissimus dorsi muscle• Medial: Sternal border• Superior: Clavicle• Inferior: Up to upper ¼ th of rectus sheath.

Raising skin flaps:The upper skin flap is raised upto the clavicle and the lower skin flap is raised upto the upper quadrant of the rectus sheath.


The fascia of the pectoralis major muscle and the overlying breast tissue are elevated off the underlying musculature.


Three important structures should be preserved:

1. Axillary vein2. Bell’s nerve(long thoracic nerve)3. Cephalic vein


COMPLICATIONS1. Seroma/ lymph collection2. Secondary infection3. Flap necrosis4. Haemorrhage5. Pain and numbness in axilla, medial side

of the arm6. Shoulder dysfunction7. Injury/thrombosis of axillary vein8. Winging of scapula9. Lymphedema of arm(few month later)


The goals of reconstructive surgery after mastectomy are wound closure & breast reconstruction.

COMMON OPTIONS:• Implant(silicon gel).• Latissimus dorsi flap (LD flap).• Transverse Rectus Abdominis Myocutaneous flap

(TRAM flap).

RECONSTRUCTION OF THE BREAST AND CHEST WALL

• Role of axillary surgery in CA breast is debated, but it is accepted that presence of metastatic disease within axillary lymph nodes is still the best single marker for prognosis.

• In early breast carcinoma, if there is no clinically apparent nodes and the disease is not multicentric, then sentinel node biopsy is considered.

• Otherwise Complete Axillary Dissection is done.

AXILLARY SURGERY

A sentinel lymph node is defined as the first lymph node to which cancer cells are most likely to spread from a primary tumour.

INDICATION: Early breast cancer with clinically node negative axilla.

SENTINEL LYMPH NODE BIOPSY

• SLN can be detected either by radioactive Tc-99m labelled sulphur colloid or Isosulfan blue dye.However combination of both gives better results.

Radioactive colloid is injected in subareolar region or near the primary tumour 2-24 hours before the surgery.

Isosulfan blue dye is injected at the time of surgery in the

same region.

A hand held gamma camera is used to identify the location of SLN.

PROCEDURE OFSENTINEL LYMPH NODE BIOPSY

(contd.)

3-4cm transverse incision is given just below the hairline of axilla.

Blunt dissection is done to visualise the dye containing lymphatics which are traced to locate the SLN.

The SLN is removed and send for histopathological examination.

INTERPRETATION:1.If –ve: No axillary block

dissection is required.2.If +ve: Axillary block

dissection is done.

SENTINEL LYMPH NODE BIOPSY

BREAST CARCINOMA:NEOADJUVANT AND

ADJUVANT THERAPIES

BySOHAM SENRoll No.- 81

NEOADJUVANTTHERAPY

Neoadjuvant therapy refers to the administration of drugs – chemotherapy or hormonal therapy

Prior to surgery For a large operable tumour With the aim to reduce the loco regional tumour

burden to make it better amendable for surgical resection.

NEOADJUVANT THERAPY

1. T3,T4 tumours2. Inflammatory breast CA3. Ipsilateral supra or infraclavicular lymph node

involvement

INDICATIONS

CLASSIFICATION

Neoadjuvant therapy

Chemotherapy Hormonal therapy

• 4 cycles of Anthracyclin followed by 4 cycles of Pacitaxel followed by surgery.

• Full course chemotherapy should be completed whether or not the growth has completely resolved, before or after surgery.

• Patients who have received full course neoadjuvant chemotherapy before surgery need not receive adjuvant chemotherapy.

NEOADJUVANT CHEMOTHERAPY

• Drugs – Trastuzumab Pertuzumab

• If one gets neoadjuvant Trastuzumab, she will likely also receive adjuvant Trastuzumab.

• Trastuzumab is not usually given at the same time as Anthracycline based chemotherapy, neither in the neoadjuvant nor the adjuvant setting.

• Pertuzumab is only used as a neoadjuvant therapy and not given after surgery.

NEOADJUVANT CHEMOTHERAPY FOR HER-2 POSITIVE PATIENTS

INDICATIONS• Women who are not candidates for chemotherapy

due to other health problems or advanced age• ER/PR-positive tumours• Low grade tumours• Invasive lobular breast cancer

Most young women with large tumours are treated with chemotherapy rather than hormone therapy, even if their tumours are ER-positive.

NEOADJUVANT HORMONAL THERAPY

DRUGS• Tamoxifen• Letrozole•Anastrozole

Duration of treatment should be up to achievement of maximal response.

NEOADJUVANT HORMONAL THERAPY

To check the response to neoadjuvant therapy, several tests are done, including –• a clinical breast exam, • a mammogram, • a breast MRI , and/or• an ultrasound.

Then, surgery is planned much in the same way as if there was no neoadjuvant therapy

AFTER NEOADJUVANT THERAPY

• When a person has neoadjuvant therapy, a pathologist checks the breast tissue removed during surgery for a pathologic response.

• Pathologic response describes how much of the tumour is left in the breast and lymph nodes after neoadjuvant therapy.

PATHOLOGIC RESPONSE

• Here neoadjuvant therapy shrinks the tumour so much that the pathologist cannot find any remaining cancer in the tissue removed during surgery.

• Gives some information about prognosis, but it does not change the treatment plan.

• pCR rates to neoadjuvant chemotherapy are highest among women with – High grade tumours Hormone receptor-negative (ER & PR -ve) tumours HER2-positive tumours (when the neoadjuvant treatment

plan includes Trastuzumab and Pertuzumab)

PATHOLOGICAL COMPLETE RESPONSE (pCR)

• Downstages the disease• Increases chances of breast conservation• Inoperable tumours may become operable• Systemic treatment (chemotherapy) starts early• Assesses response in vivo

• Inhibits a potential postsurgical growth spurt• Chemotherapy is delivered through an intact

vasculature

ADVANTAGES OF NEOADJUVANT THERAPY

ADJUVANTTHERAPY

ADJUVANT THERAPY

Adjuvant therapy for breast cancer is any treatment given after primary therapy to increase the chance of long-term disease free survival.

TYPES OF ADJUVANT THERAPY

Adjuvant therapy

Radiotherapy Systemic therapy

Chemotherapy Hormonal therapy

INDICATIONS:

ADJUVANT RADIOTHERAPY

To the Chest Wall To the Axilla• T3,T4 tumour >5cm• Residual disease-LABC • Positive margin• After conservative

surgery• High risk group• Inflammatory

carcinoma

• 4 or more nodes positive

• Extranodal spread• Axillary status not

known

1.ACCELERATED PARTIAL BREAST IRRADIATION (APBI)• APBI is generally defined as

radiation therapy that uses daily fraction doses greater than 2 cGy delivered in less than 5 weeks.

• By increasing the radiation fraction size and decreasing the target volume in a shorter period.

• Given only to the lumpectomy bed.

TYPES OF ADJUVANT RADIOTHERAPY

2.BRACHYTHERAPY• Also called Internal Radiation Therapy.• Involves placing a radioactive material inside or next to the tumour.• Higher dose of radiation can be used to treat a smaller area and in lesser time.


3.EXTERNAL RADIOTHERAPY• Sites:

Breast area Axilla (in selected

patients like if axillary dissection is not done or more than 4 positive axillary nodes)

Internal mammary Supraclavicular area

• Total dosage 5000 cGY units• 200-cGY units daily 5 days a week for 6 weeks.


4.INTRAOPERATIVE RADIOTHERAPY• Administration of low energy, high dose radiation directly to the tumour bed with minimal exposure of surrounding tissues in the operating room, right after the tumour is removed.

• Leser dose of radiation is given unlike standard radiotherapy.

• Duration: 30 mins

• Effects: Immediate sterilization of residual tumour cells. Inhibits stimulating effects of wound fluid.


(contd.)

INDICATIONS:• Age >50 years• Early stage of breast cancer (not spread)

ADVANTAGES:• All radiation in single dose.• Less dose.• Adjacent structures receive less radiation.• Less costly.

SIDE EFFECTS:• Bruising.• Increased fluid accumulation in breast tissues.

INTRAOPERATIVE RADIOTHERAPY

• Skin-May become red, dry, tender, and itchy

• Breast-May feel heavy and tight.

SIDE EFFECTS OFADJUVANT RADIOTHERAPY

Adjuvant Chemotherapy refers to administration of cytotoxic drugs to women after breast cancer surgery to eliminate undetectable distant spread.

INDICATIONS:• Tumour size >1cm• Tumour size <1cm with ER negative

HER-2 PositiveHigh grade

ADJUVANT CHEMOTHERAPY

1st LINE DRUGS:

2nd LINE DRUGS:Taxanes- Paclitaxel

Docetaxel3rd LINE DRUGS:

Gemiticabine

DRUGS USED INADJUVANT CHEMOTHERAPY

CMF regime CAF regime MMM regime

Cyclophosphamide

Cyclophosphamide

Methotrexate

Methotrexate Adriamycin Mitomycin-C

5-Fluorouracil 5-Fluorouracil Mitozantrone

REGIMES OF ADJUVANT CHEMOTHERAPY

• Given orally or by i.v. injection.

• Given in cycles, consisting of a treatment period followed by a recovery period. The number of cycles depends on the types of drugs used.

• Usually does not last for much more than 6 months.

ADMINISTRATION OFADJUVANT CHEMOTHERAPY

ADJUVANT TRASTUZUMAB THERAPY:

• Trastuzumab: A monoclonal antibody against tyrosine kinase receptor(HER-2) is administrated in patients with HER-2 +ve Patients to improve Disease Free Survival(DFS)

• Dose: Loading: 4mg/kgMaintenance: 2mg/kg for 9 weeks

• Administration: i.v. infusion every 1 to 3 weeks for a year.

ADJUVANT CHEMOTHERAPY FOR HER-2/NEU POSITIVE PATIENTS

• Infections and bruise or bleed easily, less energy loss of appetite, nausea, vomiting, diarrhoea, or mouth sores.

• Anthracyclines can increase the risk of heart problems.

• Trastuzumab can induce nausea, vomiting, hot flashes, and joint pain. It can also increase the risk of heart problems.

SIDE EFFECTS OFADJUVANT CHEMOTHERAPY

PRINCIPLES:

• It is used in ER/PR positive patient in all age groups

• It gives prophylaxis against carcinoma of opposite breast

• It is not used in ER negative Patients

ADJUVANT HORMONAL THERAPY

1st LINE: Anti oestrogen: Tamoxifen

2nd LINE: Aromatase inhibitor: Prevent the synthesis of oestrogen by

blocking aromatase inhibitor enzyme which converts androstenedione to oestradiol on adrenals.

• 1st generation: Aminoglutathemide• 2nd generation: Anastrozole, Letrozole

3rd LINE: Progestogens: Megestrol acetate

4th LINE: Androgen: Fluoxymesterone

DRUGS USED INADJUVANT HORMONAL THERAPY

• Oestrogen Receptor Antagonist• Dose: 20mg once daily for 5 years • Half life: 7 days • Used commonly in Premenopausal women • Adverse Effects:

Flushing, tachycardia, Sweating, vaginal atrophy, itching, bone pain

• Advantages: Reduces recurrence rate by 25% Equally effective in male breast carcinoma Cheap, easily available, less toxic

ADJUVANT HORMONAL THERAPY:TAMOXIFEN

• Usually given orally, as a pill.

• Most women who undergo hormonal therapy take Tamoxifen every day for 5 years.

• Some women may take an Aromatase inhibitor every day for 5 years instead of Tamoxifen.

• Some women may receive additional treatment with an Aromatase inhibitor after 5 years of Tamoxifen.

ADMINISTRATION OF ADJUVANT HORMONAL THERAPY

ADVANTAGES:• Relatively safe, easy to administer • Used in metastatic carcinoma of breast

SIDE EFFECTS:• Hot flushes, vaginal discharge, and nausea.• Tamoxifen also increases the risk of cataract

development .• Aromatase inhibitors: Hot flushes, vaginal dryness,

and other symptoms of menopause joint pain (arthralgia) or muscle pain (myalgia) during treatment.

ADJUVANT HORMONAL THERAPY

THANKYOU

Date post:	26-Jan-2017
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Breast Carcinoma

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