Early Cancer Breast Treatment

By

Prof U.K.Shrivastava

Head

Faculty of Surgery

AIMST

Malaysia

Invasive cancer,contained in breast and may

or may not have spread to draining lymph node

of breast or armpit. Some cancer cells might

have gone out of breast,or armpit ,but can not

be detected. They are– stage o, I and II cases

at times stage IIIa cases with little tethering

Early Cancer Breast

RISK Factors

Gender- woman greatest risk factor

Age- Generally 50 years and above .

Ethnicity- African American higher %

Genetic evaluation- BRCA I BRCA II ,P53

Dense breast tissues, more glandular,tissue

LCIS and DCIS

Early menarche and late menopause

Use of oral contra septics and HRT

Risk Factors

Previous exposures to chest wall radiations

Family history of ca breast , mother , sister

Personal H/O ca breast to one breast

BBD- ductal hyperplasia,sclerosing adenosis

complex fibroadenoma,pappilomatosis

Pre Operative Evaluations

Gold standard – surgeons clinical exam and

history, Risk factors

Must assess the extent of disease, local,

regional and distant sites

Mammography—types – Screening

Diagnostic

For evaluations- add. Views, compression

Magnifications,coputerised enhancement

Pre Operative Evaluations

Digital mammography –differs from analog

mammography. here images are digitized &

stored in computerized format

It can be magnified, contrast can decreased

or increased to see the pathology

ULTRASOUND– Not a very good modality

well indicated for pregnant ,juvenile and

adolescent,and with breast infections

No ionizing radiations- advantage

Pre Op Evaluations

MRI--- very useful

Interpretation based on uptake and wash

out of contrast media from breast tissue

Smooth, round, oval – mostly benign

Irregular ,speculated –malignant

MRI detect lesion up to 5mm of size

Mammography only detect 10mm of size

It detects,nipple and chest wall invasion

MRI

MRI -- very useful as screening tool in high

risk patients, especially for BRCAI II

Helpful in deciding the BCS surgery

But it is 15 times costly than Mammo

Positron Emission Tomography ---PET

It detects the patients base line

glucose level after injecting theFDG

Increase uptake worst prognosis

PET-CT

90% sensitivity for diagnosing Recurrence

Confirms distant metastasis

Evaluates the response of Neoadjuvant

chemotherapy

** Biopsy– Most important

FNAC-office procedure, least invasive

Excellent cytologist, if more tissue

Do Core biopsy U/S stereotactic Bx

Molecular markers of Breast cancer -Hormonal

Majority of cancer are Hormonal dependent

70to80%of invasive ca and all intra ductal ca

Estrogen effects mediated by ER α ERβ

Antiestrogen Tamoxifen blocks the receptor

Reduces the risk contra lateral/metastatic

Leads to38% reduction in ca breast

Doses 20mg daily for 5 years

Good for DCIS Chemoprevention high riskpt

Anti estrogen Selective Estrogen Receptor modulator

***Stilbesterol-like agents----

Raloxifen ( Evista) dose 60mg for 5 years

Known as SER Modulators

***Steroid Analogue of Estrogens--------

These compound are pure anti estrogens

Drug is Fulvestrant

Benefits- No hot flush no thrombo embolism

and low risk for uterine cancer

Aromatase Inhibitors

These are helpful in blocking synthesis

of estrogens from Androgens via

Aromatase Enzymes in post men. female

Drugs-- Anastrazole,Exemestane and

Letrazole

Benefits –Prolong DFS, OS &Reduction in

contralateral ca,Metastasis

Non Hormonal Targets cellular Markers

***Growth Factors

Epidermal growth factor imp. Role in

epithelial cell growth(EGF)

HER/erbB family includes HER1HER2

Both are related with ca breast pathogenesis

Epithelial hyperplasia & neo angiogenesis

Monoclonal antibody- Zd1839and Herceptin

Very effective for this aggressive ca breast

HerceptinTrastuzumab

HER2/new gene protein, member tyrosine

kinase receptor, amplified one third of patient.

Its presence shortens DFS and overall S

HER2/new over expression should be tested

Trastuzumab humanized monoclonal anti body

First FDA approved biological agent ca-breast

It is Not, cytotoxic, targeted therapy,

Variety of chemo. can be combined , good result with Taxane and doxirubicin

withTaxane

Cell Cycle And Apoptosis

P 53 Gene

DNA damage and hypoxia are stimuli

both activate the p53 tumor suppressor gene

Negative correlation betweenp53 positivity and

age,ER and PRstatus,Positive with Tumor grade

Activation leads to growth arrest, apoptosis

loss of p53 function with mutation –cancer

this gene get mutated with carriers of BRCA I ,II

Aggressive tumor early mets poor survival,

Vascular Endothelial Growth Factor

VEGF enhances angiogenesis, tumor growth

Tumor expressingVEGF have higher micro

vessel density and often associated ,p 53 expression.

Targeted therapy required in future to act .

to stop angiogenesis lead to tumor cell death, without causing harm to normal cells

AVASTIN--CA COLON

Hereditary Breast Cancer

BRCA I BRCA II

Discovered 1994,gene protein ,breast tissue

Helps in repairing damaged DNA ,

If mutated, damaged DNA not repaired

Uncontrolled growth occurs leading cancer

OverExpression life time risk ca breast 70%

High risk patient DNA testing is MUST

Patients with mutated genes poorer prognosis

Types of Breast Carcinoma

I Non Invasive– DCIS and LCIS

2 Invasive----- Invasive intra ductal cancer

Invasive lobular carcinoma

Paget's disease of nipple

3 Inflammatory Breast Carcinoma

4 Locally advance Breast carcinoma

5 Secondary( metastatic )Breast carcinoma

Treatment Early Breast Cancer

Non Invasive Breast Cancer

Incidence gone up due to better screening

Local disease, highly curable

BCS is ideal, than historically Mastectomy

Lumpectomy along with Radiation

BCS to be based on several factors

Size of breast,multicintric,tumor grade,

nipple areola status, genetic testing,inability

to receive radiation,pregnancy

Non Invasive cancer Breast-Treatment

DCIS lymph node involvement 1% o 3%

Positivity means undiagnosed invasive ca

if so – go for sentinel lymph node biopsy

Indications Extensive disease, high grade

doubt of invasion, plan for

Mastectomy , pts choice

Adjuvant therapy--- hormonal Tamoxifen

It is individualized

Treatment of Invasive BreastCancer

Less controversial

Treatment of choice BCS, Lumpectomy

with Radiation Axillary

sampling, in all cases

Sentinel L.NBiopsy

Those meet requirement of Mastectomy

offer them Reconstruction By Implant or by Autologous tissues TRAM ,Lattismus dorsi

Surgical Technique

Lumpectomy,Quadrnectomy Seg Mastectomy

Incision– curvilinear, close to tumor, 2 to 3mm

Margin microscopically free,Handle the

specimen carefully, Take additional tissue from

margins, Meticulous hemo stasis, No drain,

Apply micro clips for radiologist, Do not

reapproximate breast tissue for dead space

Do two layer skin closure

Mastectomy

Indicated for different sets of women—

1st Those who are not fit for BCS

2nd Those who do not wish to have BCS

3rd Those identified a high risk genetically

4th Those who do not wish Radiotherapy

Surgery-Simple mastectomy,ssm, nsm asm

CARE-preserve viability skin flap, thickness

of flap considered carefully

Mastectomy

Sentinel lymph adenectomy must be done

SSM, NSM,ASM done for reconstruction

Recurrence 3 to 10% in these group

In properly selected patients NSSM and

SSM results are equivocal in prognosis

Lot of studies on NAC preservation as they contain duct tissues –Recurrences

One should choose the case very carefully

Prophylactic Mastectomy

It is advised to women having high risk

Mostly those who are carriers of BRCA I

and BRCA II mutational genes

Life time risk general population 12.7%

compared to36%to %85with BRCA I and II

Personal history of having cancer in one

Breast 18% to 36% in contra lateral breast

Surgical principle be same as wth ca breast

Breast Reconstructive surgery Goal

• To diminish chest wall deformity• Improve the psycho social well being• Better body image, self esteem and

satisfaction

** Timing of reconstruction**

Immediate – Done along Mastectomy

Delayed----- After wound healed and

adjuvant therapy given

Immediate Reconstruction

Types of Reconstruction—

A Implant – Saline or Silicon gel

B Autologous tissues - TRAM Flap or

Lattismus dorsi muscle flap

some prefer natural looking feeling breast

where as others don’t want body morbidity

Those not willing Reconstruction ----

Breast Prosthesis-simple,&comfortable

Breast reconstruction

• Immediate—

Disadvantage- Delay in adjuvant therapy partial loss of mastectomy skin flap

for residual disease, and close surgical

margin may need radiation, can’t be done

Advanced disease stage iii and above

(ir needs radiotherapy post op)

Delayed - After mastectomy&adju. therapy

Treatment of Axillary Nodes

Lymph node metastases- prognostic factor

SLNB preferred method Axillary stagingT1-3

Those with negative reports spared from

axillary dissections

SLNB – injection of vital blue 5ccof isosulfan

intra tumoral or periareolar later, blue tinged lymph nodes removed and tested

if node positive do the axillary dissection

Debate for level I II III removal mostly I II

Axillary Dissections

Avoid skeletonizing the axillary vein.

Preserve long thoracic and throracodorsal nerve

Preserve inter costal nerve if feasible

Drain is used from a separate stab incision

SLNB positive up to .2mm –No up to 2mmNIm

Larger than 2mm NI status

No - Does not need axillary dissection, But Nim

& NI disease should go for axillary dissection

SLNB

Currently standard of care is complete

Axillary dissection for all NI(mi)and NI cases

ADJUVANT THERAPIES----

** Whole Breast Radiotherapy-----

Women opting for BCS, have to go for whole

breast radiotherapy, after lumpectomy with

negative margins , failing recurrence high

**Accelerated Partial Breast Irradiation(APBI)

Accelerated Partial Breast Irradiation

It shortens the treatment time 4 to 5 days

It is interstitial brachytherapy,by Seeds or

Needle ,Balloon catheter based,and intra-

operative radiotherapy,these method target

the lumpectomy cavity, plus1to2 cm margin

Benefit – Less irradiation to surrounding

breast tissue and normal tissue

45 to 60 Gy in4 to 6 days, very effective

Post Mastectomy Radiation

PMRT---required-

a Pts with 4to5 positive axillary nodes

b Pts with T3 Larger tumors size

c Pts with Stage III cancers

Radiation field includes-

Chest wall, and supra clavicular nodes

Avoid radiations to axilla,Int mammary

Recurrence rate goes down

PMRTFollowing groups benefit with PMRT

1 age and positive axillary nodes

2 Lympho vascular& perineural invasion

3 High Tumor grade

4 Extra capsular extension of lymph node

metastasis

5 Hormone receptor status

6 Gene expression profile,& Margin status

7 After Neoadjuvant chemo,T4 bulky T&LN

Systemic TherapyAdjuvant Chemotherapy-

Suitable to all invasive Cancer Breast

Best combined chemo than single agent

CMF 1970, CAF 1980,TAC 1990

8, 6 & 4 cycles Rpt on 21to 28 days gap

If Metastatic---

Gemcitabine with Paclitaxel

Capecitabine with Docetaxel

Dose Density Chemo 2 wks gap, growth Horm

Hormonal Therapy

Tamoxifen and Aromatase Inhibitor

* Given to all Receptor positive case

* Regardless to pts Age, Lymph node

Status, HER II and menopausal status

* It falls in Three Category-

a Blockade of estrogen activity

b Surgical or medical ovarian ablation,

c Aromatase enzyme inhibition,Letrazole

** Tamoxifen used as Chemoprevention**

Hormone Therapy

* Tamoxifen is good as adjuvant therapy

In cases having BRCAI& BRCAII genes

* For better result Anastrazole, Letrazole

aromatase inhibitors can beused in post-

menopausal period

* Given for period of 5 years

* Risk- uterine cancer,thrombo embolism

*Better-DFS,and OS ,prevents opposite ca

Endocrine Therapy Regimens Invasive cancer Breast

Premenopausal-

Tamoxifen - 10mg b.d. or 20mg o.d 5 yr

Goserelin LHRH-- Reversible ovarian suppressiopn 3.6mg s.c.every 28days 2yr

Postmenopausal--

Tamoxifen 10mg bd or 20mg od 5 yr

anastrazole 1mg daily 5 years

HER 2 Disease Treatment

HER positive cases -- aggressive., Locally

advanced and resistant to Hormonal therapy

Present in 20to 30% of all cancer Breast pts.

This targeted therapy , Decrease recurrence

and improved over all survival

Trastuzumb(Herceptin,Genentech)is a

humanized monoclonal antibody stops tumor growth, Works better with Taxane

and Anthracycles

Targeted Therapy

Another drug Lapatinib given orally

Works against epidermal growth factor and

HERII over expression gene together

Resistant to Herceptin give– Lapatinib

** Antiangiogenic Agents**

VEFG plays important role in angiogenesis

Over expression of gene flares tumor growth

Associted with higher hormone receptor genes

Tr by monoclonal antibody Avastin Bvacizumab

Vaccine

Ideal to have vaccine—

should be inexpensiv

easy to administer

well tolerated,- target only disease entity

Not to the host

Major advances in understanding of the tumor, biology are being done but nothing

has so far ,to prevent Cancer breast

THANK YOU

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