management of early breast cancer

ModeratorModeratorDr Haresh K.PDr Haresh K.P

Department of RadiotherapyDepartment of Radiotherapy

AIIMS, NEW DELHIAIIMS, NEW DELHI

MANAGEMENT OF EARLY STAGE MANAGEMENT OF EARLY STAGE BREAST CARCINOMABREAST CARCINOMA

SpeakerDr Ruchir Bhandari

Work up for Early Breast Cancer (EBC)

Includes all patients with stage I & II Diagnostic evaluation

– Tru cut biopsy – B/L Mammography,USG

Metastatic evaluation not mandatory Routine pre-anesthetic investigations

(HMG, Ser biochemistry, CXR, ECG)

Includes :

Carcinoma in situ

T 1-2 , N0-1 , Mo

Evolution Of Treatment

Extended Radical MRM MRMBCS

LRRTWBRTAPBILRRTWBRTAPBI

ChemotherapyHormonal TherapyBiological Therapy

OncotypeDx/Mammaprint/rotterdam Signature/PAM50OncotypeDx/Mammaprint/

rotterdam Signature/PAM50

QOLPsychosocial

Outcome

TYPES OF SURGERY

Simple mastectomy

Extended Radical Extended Radical mastectomymastectomy

LUMPECTOMY

Removal of tumor + surrounding margin of1-2 cm of normal breast tissue

Skin encompassing any prior biopsy site should be excised

QuadrantectomyQuadrantectomy Partial /Segmental mastectomyPartial /Segmental mastectomy Wide local excision (WLE)Wide local excision (WLE) Excision biopsy Excision biopsy

Do MRM if1.Large tumors in small breast2. EIC 3. –ve margin not attained4. Diffuse micro calcifications5. Cx of RT 6. Pt unreliable for f/u.

RECONSTRUCTIVE OPTIONS

Either by prosthesis (silicon implants) or autologous tissue transfer

Can be done in same surgery, better results if RT can be avoided

After quadrantectomy / WLELocal fat mobilizationMini LD flapExtended LD flap

After mastectomyVertical / transverse rectus abdominis flapGluteal free flap

Complications of surgeryComplications of surgery

I. Lymphoedema – 6-30%

II. Wound infection – 3-15%

III. Seroma – most frequent

IV. Tissue necrosis

V. Pneumothorax – rare

VI. Phantom breast syndrome – continued sensory

presence of breast after it has been removed

VII. Phantom pain – 17.4%

Axillary dissection Axillary dissection Axillary nodal status determines adj. CT level I & II ; 10 is minimum

cN0 20 - 40 % pN0cN+ 20 - 40 % pNO

Skip mets to level II – 15% , level III – 1-3%

Level II I dissection cN+, skin + Lymphoedema (3-5% 10-15%)

Absolute benefit of 5.4%

Orr et al, 1999

Sentinel lymph node biopsy Sentinel lymph node biopsy (SLNB)(SLNB)

should follow negative USG axilla +/- FNAC

Tc 99m sulphur colloid & isosulphan blue dye

IHC- not routine, for suspicious nodes only

50% SLN + have no mets in non SLN on ALND

Methylene blue and 99-Tc – safe in pregnancy ( NCCN 11)

subareolar and intradermal (rather than peritumoral) injection for

multicentric disease

Cx – cN+, large or multiple tumors, prior axillary Sx

NSABP B-32

RCT comparing SNB to conventional axillary dissection in

clinically node-negative breast cancer patients

5611 patients, 97% SN identification

FNR = 9.8% in pts with SN followed by ALND

Similar OS & DFS at 5yrs and 8 yrs

SABCS abstracts 2005, Lancet Oncology 2007;8:881-88

ACOSOG Z0011

• Hypothesis: Removal of SN achieves similar local control as Level I And II axillary clearance

• T1-2 N0; 1-3 SLN positive ( Not IHC detected ; Not matted LN )

• No regional nodal irradiation• Trial underpowered 891/1900 recruited

• BCS patients with <3 nodes; good

prognostic subset

• All had adjuvant radiotherapy, but No

details

• Is LC due to RT and Chemo?

Journal of Clinical Oncology

ALND (n=744)

ART (n=681)

p value

5 year OS 93.27% 92.52% p=0.3386

5 year DFS

86.90% 82.65% p=0.1788

5 year Ly.edema

28% 14% P<0.0001

5 year recurrence

0.54% 1.03%

N =180 post NACT Vs 1346 without NACT

Lower identification rates 85% Vs 89% (p=NS)

False negative rate was 12%-33% after NACT

756 N+ women ------------ NACT node negative

Procedure failed in 50 womenFNR 12.6% -- One SN

31.5% -- Two SN

SENTINA study : Lancet Oncol. 2013

Of 1737 patients, 1022 women underwent SLNB before NACT (arms A and B), with a detection rate of 99·1%. In patients ( from cN+ to ycN0 ) after NACT (arm C), the detection rate was 80·1% & FNR of 14·2%In pts having 2nd SLNB after NACT (arm B), the detection rate was 61% & FNR of 51·6%

Meta-analysis of SLNB after NACT- XING et al, BJS 2006

ACOSOG Z1071 results- Oral, 35th CTRC-AACR SABCS

SLNB - ASCO 14 recommendations

SLNB controversial for multi-centric disease, Post NACT, prior RT or SX

BCS vs MastectomyVeronesi et al: NEJM 2002

IS SURGERY

THE ONLY

TREATMENT ?

BCS vs MastectomyVeronesi et al: NEJM 2002

BCS vs Mastectomy Fischer et al , NEJM 2002 (1851 patients))

“Lumpectomy followed by breast irradiation continues to be appropriate therapy for women with breast cancer, provided that the margins of resected specimens are free of tumor and an acceptable cosmetic result can be obtained “

Prospective Randomized Trials of Lumpectomy +/- Radiotherapy

Necessity for Radiation Therapy(In Early Stage Breast Cancer)……

No subset of patients, where RT can be omitted

Absolute Absolute contraindicationscontraindications

1) MULTICENTRIC

2) Diffuse macro calcifications

3) H/o previous RT to breast

4) Pregnancy

5)Persistent +ve margins

1. Collagen vascular ds

2. Multifocality & indeterminant

calcifications

3. Tumor (>4-5 cm) in small breast

4. Breast too small / large or pendulous

Relative Relative contraindicationscontraindications

cN+ or pN+

Subareolar tumors

No risk of secondary cancers

Family h/o

High risk of systemic relapse but

need for adjuvant Rx

SAFE

RADIOTHERAPY RADIOTHERAPY

Aims –

1. To decrease chances of LR ; treats microscopic ds

2. Increase local control & hence increase survival

Postop RT - mastectomy

- lumpectomyIndications - 1. Tumor – >5cm , LVE + , gr2 / 3 , skin/ ms infiltr , EIC2. Lymph nodes – number, ECE, inadequate ALND3. Surgery – margins +ve , unknown or close4. Patient – age <35yrs , premenopausal

Radiotherapy

Recurrence –

Chest wall – 90% Axilla – 10% Supraclav lymph node

mets – 5-10% Postop RT decreases local

recurrence by 2/3rd

Recurrence Rate

Stage I 5-10%

Stage II 10-25%

Stage III 50%

Postop RT decreases recurrence rate in Stage I - <5%

Stage II - <10%Stage III – 10-15%

Adjuvant RT after Mastectomy

Adjuvant RT after BCSStratification for Radiotherapy

Supraclav lymph node RT – in pts with 4 or more +ve ALN tumor size > 4-5cm apical or central group of LN involved inadequate ALND Internal mammary nodal RT – unresolved issue Pts with pathologically +ve axilla – IMN mets<5% Relapsein IMN rare (<3%) even without RT RT leads to fibrosis & cardiac problems

RT AVOIDED >70yrs with ER+, N- , <2cms, wide-ve margins

Radiotherapy - techniqueRadiotherapy - technique Positioning –

Supine position

Breast board

For large pendulous breasts – full or partial decubitus

When arm angled >90 – ax. nodes overlap head of Humerus

Field opened at 0 degree rotation on chest wall ; Lead wire placed

on lateral border

CLD Best predictor of %age of I/L lung vol. Irradiated

by tangential fields ; Perpendicular distance from post.

tangential field edge to post part of ant chest wall at

centre of field

Beam AccessoriesBeam Accessories

1. Wedges or compensators

– Used to produce minimal

(10% or less) dose variation

from base to apex

2. Bolus – increases dose to

skin and scar after

mastectomy ; poor cosmesis

Conformal radiotherapy Supine or prone ; Spiral CT, 3mm slices I/L breast marked with wires, C/L breast displaced postr. CTV = entire breast and lumpectomy cavity including

seroma ; excludes skin, chest wall and muscles 6 MV photons ; Dose variation = 5-8 % OAR = heart, lung , C/L breast

1. Electrons – @ 85 -90% isodose line ; 9-16 MeV ; 10-20Gy

Set up - post lumpectomy volume or scar +2 cm in all directions

2. Interst it ial implant - Large breasts & deep seated tumors (>4cm ) INtraoperative ; TV = primary tumor + 2-3 cms

Skin - source distance > 5 mm

Limitation – lack of detailed HPR

3. 3D CRT or IMRT

Greater dose heterogeneity for large breasts (vol>500cm3)

50% reduction in cardiac mortality ,V20 3.4%

Dose inhomogeneity – 15MV > Co60 > 6MV

Geometric uncertaint ies : patients, clips and cavity position

BOOST TO TUMOR BED

Boost ComplicationsBoost Complications

Crit icism 3- 15% local recurrences, despite boost treatment ↑ labour/ cost

Pt inconvenience

Complications

↑ chances of s/c fibrosis

↑ telengiectasia & thinning of skin

Dreaded complication – Woody breast

Gr I/II – 25%

Gr III – 5-10%

EORTC Boost Trial

• 5318 patients randomized to a 16 Gy boost or no boost after 50 Gy to whole breast– Mainly CS T1-2 N0; no tumor on ink

• Boost reduced 5-yr LR by 41%; absolute benefit only 2.5% at 5 yrs• 10yr local recurrence : 6.2 % Vs 10.2 % Survival at 10 yrs: 82% for both arms

• This proportional reduction seen in all subsets

Bartelink et al. NEJM 345: 1378, 2001

Age No Boost Boost

< 40 23.9% 13.5%

41-50 12.5% 8.7%

51-60 7.8% 4.9%

> 60 7.3% 3.8%Jones et al. J Clin Oncol; 27:4939-4947 2009

High Grade

Intd / low Grade

3232

Better Local Control with RT Boost

Acta Oncologica 2007; 46:879 - 892

2657

2661

Current issues in radiation therapy

Treatment Volume: Whole breast or Partial breast irradiationInternal Mammary node irradiation

Fractionation: Standard or Hypofractionation Indications of radiotherapy in early breast cancer:

Need of radiation for 1-3 lymph node + patients Radiotherapy as an alternative to ALND in SLNB+ cases.

Treatment Techniques: WBRT/LRRT: Tangential techniques or IMRT; APBI: EBRT/Mammosite/Interstitial brachytherapy

Sequence of Radiation with chemotherapy

Internal mammary nodal RT

Routine use controversial ; Clinical failures rare If axilla +ve – 30% IMN involved (else 10%) Indications – medial / central tumors, large (>3cm) or high grade OR

radiologically positive Irradiates more critical structures (lung & heart) ; C/L Breast No difference in DFS or OS TECHNIQUE : 1. WIDE tangentials – medial border – 3cm across midline

2. Separate field – from midline to 5-6cms laterally & superiorly from 1st ICS to cover 1st three IMNs

3. Electrons

45-50Gy (1.8-2Gy/day) Mixed photons and electrons Depth @ 4- 5cms

APBI : Advantages APBI : Advantages

Improves underuti l izat ion of BCT

Avoids prolonged Rx regimens, more acceptable

Reduces t ime, cost and inconvenience

Improves QOL & Reduces acute & chronic toxicity

Eliminates scheduling problems with CT / HT

Selection criteria

1Arthur, et al. Accelerated partial breast irradiation: an updated report from the American Brachytherapy Society. Brachytherapy, 1:184-190, 2003.

2Consensus statement for accelerated partial breast irradiation. The American Society of Breast Surgeons. April 30, 2003.

Consensus Guidelines: ASTRO Smith et aI Int. J. Radiation Oncology Biol. Phys 2009,74(4): 987–1001

Methods Of APBI

Interstitial Brachytherapy --- HDR or LDR

Balloon Brachytherapy --- MammoSite

Intra-op Low-energy X-Rays--- Intrabeam

Intra-op Electrons --- Mobetron

Conformal EBRT --- 3D-CRT , IMRT

& Protons

Partial Breast Irradiation

SAVI SAVI

Mammosite TARGIT

Rando m

ize d tr ials of AP

BI

One time treatment with INTRABEAM® (TARGIT trial )

BCS +IORT

Current treatment methodCurrent treatment method

6-week irradiationBCS

IORT Boost with INTRABEAM®

BCS +IORT

4-week post-op irrad.

Percutaneous boost

4 weeks

Boost

1 day

6 weeks

INTRABEAM IORT IN BCS

04/06/15 AIIMS 42

START A Trial

•N=2236•pT1-3a,pN0-1 M0

• requiring radiotherapy after surgery (breast-conserving surgery or mastectomy

•with clear tumour margins ≥1 mm• aged over 18 years,•did not have an immediate surgical reconstruction • available for follow-up

•N=2236•pT1-3a,pN0-1 M0



RANDOMIZATION

RANDOMIZATION

50 Gy/25#/5 weeks50 Gy/25#/5 weeks

41.6Gy/13#/5 weeks41.6Gy/13#/5 weeks


14% received LRRTBOOST- 10Gy61% received BOOST

14% received LRRTBOOST- 10Gy61% received BOOST

The principal end points: local-regional relapse, normal tissue effects, and quality of life

04/06/15 AIIMS 43

START B Trial

•N=2215•pT1-3a,pN0-1 M0



•N=2215•pT1-3a,pN0-1 M0



RANDOMIZATION

RANDOMIZATION


40Gy/15#/3 weeks40Gy/15#/3 weeks

14% received LRRTBOOST- 10Gy

14% received LRRTBOOST- 10Gy

The principal end points: local-regional relapse, normal tissue effects, and quality of life

43% received BOOST43% received BOOST

Loco-regional recurrence is not different in the 50

Gy and 40 Gy arm

Disease free Survival

Disease free survival is not different in the 50 Gy

and 40 Gy arm

First results of the randomised UK FAST Trial of radiotherapy hypo-fractionation

for treatment of early breast cancer (CRUKE/04/015)

5 weeks and 1 week treatment associated with

equal disease control

ASTRO guidelines for fractionation Int. J. Radiation Oncology Biol. Phys.; 81(1):59–68, 2011

IMPORTHigh

IMPORTLow

SHARE RTOG

# Pts 840 2100 2796 2150

Sites UK UK France US

Arms Gy x #

2.4 x 15 (+ concurrent

12 gy or 17 Gy Boost)

vs2.67 x 15 (+16 Gy seq. boost)

2.67 x 15 WB vs

2.4 x 15 WB + Conc. Boost

vs2.67 x 15 APBI

2 x 25 WB +2 x 8 seq

vs2.67 x 15 WB

vsAPBI4 x 10

2 x 25+ seq boost

VS2.67 x 15 +

conc. Boost

No Consensus on the use of PMRT 1-3 LN +ve Pts.

Uncertain : NIH Consensus Statement 2000ASCO Guidelines, JCO 2001ACR Appropriateness criteria, IJROBP, 2009

PMRT strongly considered in patients with 1-3 positive nodes [NCCN 2012]PMRT indicated inn 1-3 LN with any risk factor ( ECE, LVI , young age< 50, inadequate ALND) [ 8 t h WCI-TMH ]

10yr LRR in 1-3 LN +veM D Anderson: 12%ECOG: 13%NSABP: 6-11%IBCSG : 14-27%

PMRT in 1-3 LN +ve

Nodal ratio >0.20 LRR >20% consider PMRT

BCG MDACC p

10-year LRR 21.5% 12.6% =0.02

10-year LRR : NR≤0.20

17.7% 10.9% =0.07

10-year LRR : NR>0.20

28.7% 22.7% =0.32Pauline et al. IJROBP 2007

- DBCG 82 b & c- Overgaard et al, 2007

Survival benefit after PMRT was substantial and similar in patients with 1–3 and 4+ LN

PMRT No PMRT p

15-yrs LRFR;4+ N 10% 51% <0.001

15-yr LRFR;1-3+ N 4% 27% <0.001

15-yrs OS; 4+N 21% 12% =0.03

15-yrs OS; 1-3+N 57% 48% =0.03

The MA.20 Trial (NCIC-CTG)

1832 High risk N+/- underwent BCS + Chemo + HT 1-3 positive nodes = 85% ; > 4 positive nodes = 5%

WBI+RNI improves 5yr LR DFS ( 96.8% & 94.5% )distant DFS ( 92.4% & 87.0% ) OS ( 92.3% & 90.7%)

a/w gr 2 pneumonitis ; lymphedema.

Whelan T.J., et al, ASCO 2011 Oral presentation

Sequencing RT & CCT

A Cochrane review: 3 RCTs sequencing of CT & RT do not appear to have a major effect on survival or recurrence for women with breast cancer if RT starts within 7 months after surgery.

- Hickey BE, et al. 2006

Adjuvant systemic therapy : Why required Adjuvant systemic therapy : Why required ??

Stage 5 yr survival

Stage I 80%

Stage II 50%

Stage III <30%

Stage IV <10%

Micro metastasis common at time of dx

Major threat of distant mets

CCT more effective than Tmx in younger

pts

Taxanes max benefit in Her2 +ve , N+

Results of loco regional t/t by surgery & RT

Indications Indications

All pts with node + axilla Node –ve axilla with -

1. Tumor size >1cm

2. Grade 2-3 tumors

3. Young women

4. Surgical margins – close , +ve or unknown

5. Lympho-vascular emboli

6. High proliferative index

7. ER/PR - -ve

Progress in Chemotherapy for Early Stage Progress in Chemotherapy for Early Stage Breast CancerBreast Cancer

Combination chemotherapy (CMF)

Use of anthracyclines

Addition of taxanes

Superior taxane containing regimens

Addition of trastuzumab

1970s

2000s

BUT: ALL chemotherapy is associated with toxicities and risks… need better ways to identify which patients will benefit from treatment

Improved survival with poly CT; 15 yrs FU

Anthra. adds benefit in unselected N+ve tumors

5yr DFS 65% vs 70 %

5yr OS 77% vs 80 %

EBCTG 2005

Peto et al, 2007

CALGB 9344

5yr OS benefit of 5.1%

EBCTG ‘05

TAXANES

EBCTG ‘05

GENOMIC PROFILING early breast cancer, N- , ER+ve, Her2 –ve

1.Oncotype Dx - - 21 gene signature, RT-PCR on 21 gene signature, RT-PCR on formalin fixed specimenformalin fixed specimen Prognostic , predictive risk of 10 yr DRPrognostic , predictive risk of 10 yr DR

2. 2. Mammaprint- 70 gene signature, paraffin fixed OR - 70 gene signature, paraffin fixed OR Fresh tissue ; Can be used for ER- and Fresh tissue ; Can be used for ER- and

Her2 +ve tumors as wellHer2 +ve tumors as well

3. 3. PAM50 (risk of recurrence score) – 50 genes (risk of recurrence score) – 50 genes4. 4. Rotterdam 76 gene signatureRotterdam 76 gene signature5. Genomic grade index5. Genomic grade index6. Breast cancer index6. Breast cancer index

RXpONDER Trial – evaluating benfit in 1-3 node+ disease

ERA OF PERSONALISED

MEDICINE

Endocrine therapies

Selective Estrogen Receptor Modulators:– Tamoxifen– Torimefene

Androgens– Fluoxymesterone

Progestins– Megestrol acetate– Medroxyprogesterone

acetate High dose Estrogens

Aromatase inhibitors :– Letrozole– Anastrazole– Exemestane

Steroidal Antiestrogens:– Fulvestrant

LHRH agonists– Leuprolide– Goserelin

Gland ablation– Ovary/pituitary/adrenal

Hormonal management – A balance

Fracture fatigue Hot flush Hot flush

Endometrial carcinomaThrombo-embolism

Aromatase InhibitorsNon-Steroidal

AnastrozoleLetrozole

SteroidalExemestane

Tamoxifen

ATAC- No OS benefitBIG 1-98- 4% OS benifit

IES 2.1% OS benefitARNO-95- 2.3% OS benifit

ATAC- No OS benefitBIG 1-98- 4% OS benifit

IES 2.1% OS benefitARNO-95- 2.3% OS benifit

Switch /Mono-therapy

Tamoxifen Competitive antagonist of estrogen

EBCTCG ,1998 :

47% - fewer recurrences

26% less mortality

Absolute OS benefit @ 5 yrs in N+ and N- by 10.9% & 5.6%

Decrease risk of C/L breast Ca regardless of ER/PR status, age

Positive effect on bone density

NSABP B23 – no benefit in ER/PR-

Receptor status

Response rate (%)

ER+/PR+ 70

ER+/PR- 50

ER-/PR+ 40

ER-/PR- <10

1 of every 2 recurrences 1 of every 3 deaths

Pre or peri menopausal women intolerant to tamoxifen OR want to preserve fertility offer ovarian suppression ( triptorelin) with AI [OS+ AI better than OS+T]

- SOFT trial , IBCSG, ASCO 2014 - TEXT trial, IBCSG , ASCO 2014

Aromatase InhibitorsAromatase Inhibitors Prevent periph conversion of androgens to estrogen selective

estrogen deprivation without impairment of adr. androgen synth.

No AI found superior to another *

Less S/E than Tmx, more efficacy in postmenop.

* absolute 2.9% decrease in recurrence & 1.1% OS benefit (NS) absolute 2.9% decrease in recurrence & 1.1% OS benefit (NS)

– metaanalysis; Dowsett, JCO 2010

- BIG 1-98 trial, ATAC Trial

3 generations

1st : Aminoglutethemide

2nd: Formestane (Type I) ,

Fadrazole

3rd : Exemestane (Type I) ,

Anastrazole , Letrozole,

Vorozole* NCI-CTG MA.27 trial, 2013

Effect of anastrozole and tamoxifen as adjuvant treatmentfor early-stage breast ca: 10-yr analysis of the ATAC trial

Jack Cuzick et al, Lancet Oncol 2010

Anastrazole showed significant benefit in terms of DFS, LR or DM but Fractures were more common

Five Years of Letrozole Compared With Tamoxifen As Initial Adjuvant Therapy for Postmenopausal Women With Endocrine-Responsive Early Breast

Cancer: Update of Study BIG 1-98

Alan S. Coates et al, JCO, 2007

PFS significantly better, without impact on OS

ATLAS Trial aTTOM Trial

OPTIMAL DURATION OF TAMOXIFEN TREATMENT ?

Hormonal ManagementAdjuvant treatment - In ER+/PR+, her2neu3+/-treatment options

ASCO, JCO,2014

Ovarian ablationOvarian ablation– Types – surgical / radiation / medical

– Scottish trial: Ovarian ablation was equally effective as adjuvant CCT with CMF In ER +ve women a trend towards better survival was found with

ovarian ablation– ZEBRA trial:

Goserelin ( x 2yrs) was as effective as CMF ( x 6 cycles) in ER +ve, stage II & node +ve patients.

In the ER –ve subgroup CMF had better OS and DFS.

Thus at best, ovarian ablation is as good as CMF based CCT ( but not better) in the ER +ve premenopausal females with early stage disease.

TechniqueTechnique Position: Supine Field selection: Parallel opposing two field technique Energy : Co60 or 6 MV LINAC Dose Schedules:

– In a younger women 10 – 12 Gy in 5 -6 divided fractions is preferred.

– In older women shorter course of radiation can give equivalent ovarian ablation.

Field borders:– The volume of interest is the entire true pelvis– 10 x 15 cm field is opened.– Lower border is placed just below the superior border of pubic

symphysis.

Study design- Bolero II

RANDOMIZATION

•multicenter, •open-label•phase III study•N=724•Randomization2:1 ratio

Exemestane 25 mg OD +Placebo 20 mg/d

Exemestane 25 mg OD + everolimus 10 mg/d.

March 2008 and May 2009,

• The primary end point PFS• Secondary end points: overall survival, overall responserate, clinical benefit rate, time to deteriorationof ECOG performance status, safety, and quality of life

• The primary end point PFS• Secondary end points: overall survival, overall responserate, clinical benefit rate, time to deteriorationof ECOG performance status, safety, and quality of life

• At least one measurable lesion or mainly lytic bone lesions in the absence of measurable disease

• Exclusion criteria included a history of brain metastases and previous treatment with exemestane or mTOR inhibitors

• At least one measurable lesion or mainly lytic bone lesions in the absence of measurable disease

• Exclusion criteria included a history of brain metastases and previous treatment with exemestane or mTOR inhibitors

Hormonal

resistance

Over expression > 50% DCIS and approx 1/3 rd IDC

Shortened Median Survival

HER2 over expression 3 yrs

HER2 normal 6-7 yrs

Transtuzumab binds to extra-

cellular membrane domain of

Her2 and inhibits signalling and

proliferation

Trastuzumab: Humanized Anti-HER-2 Monoclonal Antibody

Trastuzumab significantly reduces the risk of recurrence and prolongs OSConcurrent administration superior to sequential (NCCTG/NSABP B-31)A reduction in recurrence also seen with sequential administration (HERA)

Safety issues with trastuzumab include

− Cardiotoxicity, Hypersensitivity, Anaphylaxis

NSABP B31 / N 9831 (2012) OS benefit was significant for ≥ 60 yrs (13.7%), ≥ 10 Nodes + (15.6%), and tumors ≥ 5.0 cm (11.8%).

Thank you

management of early breast cancer

Health & Medicine

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