1. Early Cancer Breast
Treatment
By
Prof U.K.Shrivastava
Head
Faculty of Surgery
AIMST
Malaysia

2. Early Cancer Breast
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

3. 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

4. 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

5. 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

6. 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

7. 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

8. 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

9. 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

10. 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

11. 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

12. 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

13. 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

14. Herceptin
Trastuzumab
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

15. 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,

16. 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

17. 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

18. 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

19. 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

20. 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

21. 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

22. 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

23. 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

24. 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

25. 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

26. 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

27. 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

28. 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

29. 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

30. 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

31. 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)

32. 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

33. 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

34. PMRT
Following 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

35. Systemic Therapy
Adjuvant 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

36. 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**

37. 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

38. 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

39. 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

40. 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

41. 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

42. THANK YOU
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