SlideShare ist ein Scribd-Unternehmen logo
1 von 74
Downloaden Sie, um offline zu lesen
ModeratorModerator
Dr Haresh K.PDr Haresh K.P
Department of RadiotherapyDepartment of Radiotherapy
AIIMS, NEW DELHIAIIMS, NEW DELHI
MANAGEMENT OF EARLY STAGEMANAGEMENT OF EARLY STAGE
BREAST CARCINOMABREAST CARCINOMA
Speaker
Dr 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
MRMBCS
LRRTWBRTAPBILRRTWBRTAPBI
ChemotherapyHormonal
TherapyBiological Therapy
OncotypeDx/Mammaprint/
rotterdam Signature/PAM50
OncotypeDx/Mammaprint/
rotterdam Signature/PAM50
QOL
Psychosocial
Outcome
TYPES OF SURGERY
Simple mastectomy
Extended RadicalExtended 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 biopsyExcision biopsy
Do MRM if
1.Large tumors in small breast
2. EIC
3. –ve margin not attained
4. Diffuse micro calcifications
5. 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 / WLE
Local fat mobilization
Mini LD flap
Extended LD flap
 After mastectomy
Vertical / transverse rectus abdominis flap
Gluteal 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 dissectionAxillary dissection
 Axillary nodal status determines  adj. CT
 level I & II ; 10 is minimum
cN0  20 - 40 % pN0
cN+  20 - 40 % pNO
 Skip mets to level II – 15% ,
level III – 1-3%
 Level III dissection  cN+, skin +
 Lymphoedema (3-5%  10-15%)
Absolute benefit of 5.4%
Orr et al, 1999
Sentinel lymph node biopsySentinel 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?
management of early breast cancer
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 women
FNR 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 Mastectomy
Veronesi et al: NEJM 2002
IS SURGERY
THE ONLY
TREATMENT ?
BCS vs Mastectomy
Veronesi 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
AbsoluteAbsolute
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
RelativeRelative
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
RADIOTHERAPYRADIOTHERAPY
Aims –
1. To decrease chances of LR ; treats microscopic ds
2. Increase local control & hence increase survival
Postop RT - mastectomy
- lumpectomy
Indications -
1. Tumor – >5cm , LVE + , gr2 / 3 , skin/ ms infiltr , EIC
2. Lymph nodes – number, ECE, inadequate ALND
3. Surgery – margins +ve , unknown or close
4. 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 BCS
Stratification 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. Interstitial 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 uncertainties : patients, clips and cavity position
BOOST TO TUMOR BED
Boost ComplicationsBoost Complications
Criticism
 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 irradiation
Internal 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 : AdvantagesAPBI : Advantages
 Improves underutilization of BCT
 Avoids prolonged Rx regimens, more acceptable
 Reduces time, cost and inconvenience
 Improves QOL & Reduces acute & chronic toxicity
 Eliminates scheduling problems with CT / HT
Selection criteria
1
Arthur, et al. Accelerated partial breast irradiation: an updated report from the American
Brachytherapy Society. Brachytherapy, 1:184-190, 2003.
2
Consensus 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
RandomizedtrialsofAPBI
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
• 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
R
A
N
D
O
M
I
Z
A
T
I
O
N
R
A
N
D
O
M
I
Z
A
T
I
O
N
50 Gy/25#/5 weeks50 Gy/25#/5 weeks
41.6Gy/13#/5 weeks41.6Gy/13#/5 weeks
39 Gy/13#/5 weeks39 Gy/13#/5 weeks
14% received LRRT
BOOST- 10Gy
61% received BOOST
14% received LRRT
BOOST- 10Gy
61% 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
• 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=2215
•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
R
A
N
D
O
M
I
Z
A
T
I
O
N
R
A
N
D
O
M
I
Z
A
T
I
O
N
50 Gy/25#/5 weeks50 Gy/25#/5 weeks
40Gy/15#/3 weeks40Gy/15#/3 weeks
14% received LRRT
BOOST- 10Gy
14% received LRRT
BOOST- 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
IMPORT
High
IMPORT
Low
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)
vs
2.67 x 15 (+16
Gy seq. boost)
2.67 x 15 WB
vs
2.4 x 15 WB +
Conc. Boost
vs
2.67 x 15 APBI
2 x 25 WB +
2 x 8 seq
vs
2.67 x 15 WB
vs
APBI
4 x 10
2 x 25
+ seq boost
VS
2.67 x 15 +
conc. Boost
No Consensus on the use of PMRT
1-3 LN +ve Pts.
Uncertain :
NIH Consensus Statement 2000
ASCO Guidelines, JCO 2001
ACR 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) [ 8th
WCI-TMH ]
10yr LRR in 1-3 LN +ve
M 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 requiredAdjuvant 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
IndicationsIndications
 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 StageProgress 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
management of early breast cancer
GENOMIC PROFILING
early breast cancer, N- , ER+ve, Her2 –ve
1.Oncotype Dx -- 21 gene signature, RT-PCR on21 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- andFresh 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 genes
4.4. Rotterdam 76 gene signatureRotterdam 76 gene signature
5. Genomic grade index5. Genomic grade index
6. 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
carcinoma
Thrombo-embolism
Aromatase Inhibitors
Non-Steroidal
Anastrozole
Letrozole
Steroidal
Exemestane
Tamoxifen
ATAC- No OS benefit
BIG 1-98- 4% OS benifit
IES 2.1% OS benefit
ARNO-95- 2.3% OS benifit
ATAC- No OS benefit
BIG 1-98- 4% OS benifit
IES 2.1% OS benefit
ARNO-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 treatment
for 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 Management
Adjuvant 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
R
A
N
D
O
M
I
Z
A
T
I
O
N
•multicenter,
•open-label
•phase III study
•N=724
•Randomization
2:1 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 response
rate, clinical benefit rate, time to deterioration
of ECOG performance status, safety, and quality of life
• The primary end point PFS
• Secondary end points: overall survival, overall response
rate, clinical benefit rate, time to deterioration
of 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
AIIMS
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 OS
Concurrent 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

Weitere ähnliche Inhalte

Was ist angesagt?

RADIOTHERAPY FOR ENDOMETRIUM AND CERVICAL CANCERS
RADIOTHERAPY FOR ENDOMETRIUM AND CERVICAL CANCERSRADIOTHERAPY FOR ENDOMETRIUM AND CERVICAL CANCERS
RADIOTHERAPY FOR ENDOMETRIUM AND CERVICAL CANCERSKanhu Charan
 
BCT - AIIMS Experience
BCT - AIIMS ExperienceBCT - AIIMS Experience
BCT - AIIMS Experienceguest8887a7
 
New Advances in Treating Breast Cancer
New Advances in Treating Breast CancerNew Advances in Treating Breast Cancer
New Advances in Treating Breast CancerDr. Balamurugan
 
Breast oncoplastic surgery
Breast oncoplastic surgery Breast oncoplastic surgery
Breast oncoplastic surgery Fadi Alnehlaoui
 
Locally advanced breast cancer management
Locally advanced breast cancer managementLocally advanced breast cancer management
Locally advanced breast cancer managementadityasingla007
 
Cervix landmark trials- kiran
Cervix landmark trials- kiran   Cervix landmark trials- kiran
Cervix landmark trials- kiran Kiran Ramakrishna
 
Treatment of Cancer of the Esophagus
Treatment of Cancer of the EsophagusTreatment of Cancer of the Esophagus
Treatment of Cancer of the EsophagusRobert J Miller MD
 
Radiotherapy in carcinoma breast
Radiotherapy in carcinoma breastRadiotherapy in carcinoma breast
Radiotherapy in carcinoma breastSailendra Parida
 
Update on Management of Breast cancer
Update on Management of Breast cancerUpdate on Management of Breast cancer
Update on Management of Breast cancerMakafui Yigah
 
Management of axilla in carcinoma breast
Management of axilla in carcinoma breastManagement of axilla in carcinoma breast
Management of axilla in carcinoma breastSagar Raut
 
Oncoplastic breast surgery
Oncoplastic breast surgeryOncoplastic breast surgery
Oncoplastic breast surgeryKundan Singh
 
EVOLUTION OF CHEMOTHERAPY IN BREAST CANCER
EVOLUTION OF CHEMOTHERAPY IN BREAST CANCEREVOLUTION OF CHEMOTHERAPY IN BREAST CANCER
EVOLUTION OF CHEMOTHERAPY IN BREAST CANCERIsha Jaiswal
 
Basic Principles of Oncoplastic breast surgery
Basic Principles of Oncoplastic breast surgeryBasic Principles of Oncoplastic breast surgery
Basic Principles of Oncoplastic breast surgeryDr.Bhavin Vadodariya
 
Landmark trials in breast Cancer surgery - NSABP 04,06,MILAN,EORTC 10853, ECO...
Landmark trials in breast Cancer surgery - NSABP 04,06,MILAN,EORTC 10853, ECO...Landmark trials in breast Cancer surgery - NSABP 04,06,MILAN,EORTC 10853, ECO...
Landmark trials in breast Cancer surgery - NSABP 04,06,MILAN,EORTC 10853, ECO...Dr.Bhavin Vadodariya
 

Was ist angesagt? (20)

RADIOTHERAPY FOR ENDOMETRIUM AND CERVICAL CANCERS
RADIOTHERAPY FOR ENDOMETRIUM AND CERVICAL CANCERSRADIOTHERAPY FOR ENDOMETRIUM AND CERVICAL CANCERS
RADIOTHERAPY FOR ENDOMETRIUM AND CERVICAL CANCERS
 
BCT - AIIMS Experience
BCT - AIIMS ExperienceBCT - AIIMS Experience
BCT - AIIMS Experience
 
CA ENDOMETRIUM-KIRAN.pptx
CA ENDOMETRIUM-KIRAN.pptxCA ENDOMETRIUM-KIRAN.pptx
CA ENDOMETRIUM-KIRAN.pptx
 
New Advances in Treating Breast Cancer
New Advances in Treating Breast CancerNew Advances in Treating Breast Cancer
New Advances in Treating Breast Cancer
 
Breast oncoplastic surgery
Breast oncoplastic surgery Breast oncoplastic surgery
Breast oncoplastic surgery
 
Management of Rectal Carcinoma
Management of Rectal Carcinoma Management of Rectal Carcinoma
Management of Rectal Carcinoma
 
Locally advanced breast cancer management
Locally advanced breast cancer managementLocally advanced breast cancer management
Locally advanced breast cancer management
 
Radiotherapy breast
Radiotherapy breastRadiotherapy breast
Radiotherapy breast
 
Land mark trials gastric cancer
Land mark trials gastric cancerLand mark trials gastric cancer
Land mark trials gastric cancer
 
Cervix landmark trials- kiran
Cervix landmark trials- kiran   Cervix landmark trials- kiran
Cervix landmark trials- kiran
 
Treatment of Cancer of the Esophagus
Treatment of Cancer of the EsophagusTreatment of Cancer of the Esophagus
Treatment of Cancer of the Esophagus
 
Radiotherapy in carcinoma breast
Radiotherapy in carcinoma breastRadiotherapy in carcinoma breast
Radiotherapy in carcinoma breast
 
Update on Management of Breast cancer
Update on Management of Breast cancerUpdate on Management of Breast cancer
Update on Management of Breast cancer
 
Management of axilla in carcinoma breast
Management of axilla in carcinoma breastManagement of axilla in carcinoma breast
Management of axilla in carcinoma breast
 
Early breast cancer
Early breast cancerEarly breast cancer
Early breast cancer
 
Oncoplastic breast surgery
Oncoplastic breast surgeryOncoplastic breast surgery
Oncoplastic breast surgery
 
Portec trial ppt
Portec trial pptPortec trial ppt
Portec trial ppt
 
EVOLUTION OF CHEMOTHERAPY IN BREAST CANCER
EVOLUTION OF CHEMOTHERAPY IN BREAST CANCEREVOLUTION OF CHEMOTHERAPY IN BREAST CANCER
EVOLUTION OF CHEMOTHERAPY IN BREAST CANCER
 
Basic Principles of Oncoplastic breast surgery
Basic Principles of Oncoplastic breast surgeryBasic Principles of Oncoplastic breast surgery
Basic Principles of Oncoplastic breast surgery
 
Landmark trials in breast Cancer surgery - NSABP 04,06,MILAN,EORTC 10853, ECO...
Landmark trials in breast Cancer surgery - NSABP 04,06,MILAN,EORTC 10853, ECO...Landmark trials in breast Cancer surgery - NSABP 04,06,MILAN,EORTC 10853, ECO...
Landmark trials in breast Cancer surgery - NSABP 04,06,MILAN,EORTC 10853, ECO...
 

Andere mochten auch

Breastcarcinomafinal 160229134353
Breastcarcinomafinal 160229134353Breastcarcinomafinal 160229134353
Breastcarcinomafinal 160229134353mhm hewage
 
Modified radical mastectomy
Modified radical mastectomyModified radical mastectomy
Modified radical mastectomyJaideep Pradeep
 
Management of carcinoma breast2013
Management of carcinoma breast2013Management of carcinoma breast2013
Management of carcinoma breast2013Sumer Yadav
 
Mastectomy and Breast Cancer
Mastectomy and Breast CancerMastectomy and Breast Cancer
Mastectomy and Breast CancerULVAN OZAD
 
Breast CA by Dr. Celine Tey
Breast CA by Dr. Celine TeyBreast CA by Dr. Celine Tey
Breast CA by Dr. Celine TeyDr. Rubz
 
Breast cancer ppt
Breast cancer pptBreast cancer ppt
Breast cancer pptdrizsyed
 
Clinical management of breast cancer
Clinical management of breast cancerClinical management of breast cancer
Clinical management of breast cancerAndrea Spinazzola
 
Breast Cancer.ppt
Breast Cancer.pptBreast Cancer.ppt
Breast Cancer.pptShama
 

Andere mochten auch (10)

Breastcarcinomafinal 160229134353
Breastcarcinomafinal 160229134353Breastcarcinomafinal 160229134353
Breastcarcinomafinal 160229134353
 
Modified radical mastectomy
Modified radical mastectomyModified radical mastectomy
Modified radical mastectomy
 
Mastectomy
MastectomyMastectomy
Mastectomy
 
Management of carcinoma breast2013
Management of carcinoma breast2013Management of carcinoma breast2013
Management of carcinoma breast2013
 
Mastectomy and Breast Cancer
Mastectomy and Breast CancerMastectomy and Breast Cancer
Mastectomy and Breast Cancer
 
Breast Cancer
Breast CancerBreast Cancer
Breast Cancer
 
Breast CA by Dr. Celine Tey
Breast CA by Dr. Celine TeyBreast CA by Dr. Celine Tey
Breast CA by Dr. Celine Tey
 
Breast cancer ppt
Breast cancer pptBreast cancer ppt
Breast cancer ppt
 
Clinical management of breast cancer
Clinical management of breast cancerClinical management of breast cancer
Clinical management of breast cancer
 
Breast Cancer.ppt
Breast Cancer.pptBreast Cancer.ppt
Breast Cancer.ppt
 

Ähnlich wie management of early breast cancer

Marc Wigoda : Radiotherapy of the Axilla in Early Breast Cancer : When and H...
Marc Wigoda :  Radiotherapy of the Axilla in Early Breast Cancer : When and H...Marc Wigoda :  Radiotherapy of the Axilla in Early Breast Cancer : When and H...
Marc Wigoda : Radiotherapy of the Axilla in Early Breast Cancer : When and H...breastcancerupdatecongress
 
Advanced&metastatic breast cancer
Advanced&metastatic breast cancerAdvanced&metastatic breast cancer
Advanced&metastatic breast cancerMahran Alnahmi
 
Post mastectomy Radiotherapy with trails
Post mastectomy Radiotherapy with trailsPost mastectomy Radiotherapy with trails
Post mastectomy Radiotherapy with trailsAnban Bala
 
Surgical persrective in lung cancer
Surgical persrective in lung cancerSurgical persrective in lung cancer
Surgical persrective in lung cancerHarilal Nambiar
 
Small cell lung cancer staging and management
Small cell lung cancer staging and  managementSmall cell lung cancer staging and  management
Small cell lung cancer staging and managementSatyajitPradhanMPMMC
 
Radiotherapy In Carcinoma Of The Breast
Radiotherapy In Carcinoma Of The BreastRadiotherapy In Carcinoma Of The Breast
Radiotherapy In Carcinoma Of The Breastfondas vakalis
 
Updates in Radiotherapy for Breast Cancer
Updates in Radiotherapy for Breast CancerUpdates in Radiotherapy for Breast Cancer
Updates in Radiotherapy for Breast Cancerspa718
 
Ca Cervix Dr Naresh Jakhotia
Ca Cervix Dr Naresh JakhotiaCa Cervix Dr Naresh Jakhotia
Ca Cervix Dr Naresh Jakhotiadrnareshjakhotia
 
ADJUTANT RADIOTHERAPY IN BREAST CANCER
ADJUTANT RADIOTHERAPY IN BREAST CANCER ADJUTANT RADIOTHERAPY IN BREAST CANCER
ADJUTANT RADIOTHERAPY IN BREAST CANCER Nora Essam
 
Part ii management of testicular carcinoma - dr vandana
Part ii   management of testicular carcinoma - dr vandanaPart ii   management of testicular carcinoma - dr vandana
Part ii management of testicular carcinoma - dr vandanaDr Vandana Singh Kushwaha
 
BALKAN MCO 2011 - A. Eniu - How to optimize systemic therapy in LABC
BALKAN MCO 2011 - A. Eniu - How to optimize systemic therapy in LABC BALKAN MCO 2011 - A. Eniu - How to optimize systemic therapy in LABC
BALKAN MCO 2011 - A. Eniu - How to optimize systemic therapy in LABC European School of Oncology
 
Management Of Early Stage Ca Cervix [Autosaved]
Management Of Early Stage Ca Cervix [Autosaved]Management Of Early Stage Ca Cervix [Autosaved]
Management Of Early Stage Ca Cervix [Autosaved]PGIMER, AIIMS
 
BALKAN MCO 2011 - J. Zgajnar and M. Margaritoni - Surgery (SLNB, management o...
BALKAN MCO 2011 - J. Zgajnar and M. Margaritoni - Surgery (SLNB, management o...BALKAN MCO 2011 - J. Zgajnar and M. Margaritoni - Surgery (SLNB, management o...
BALKAN MCO 2011 - J. Zgajnar and M. Margaritoni - Surgery (SLNB, management o...European School of Oncology
 

Ähnlich wie management of early breast cancer (20)

Marc Wigoda : Radiotherapy of the Axilla in Early Breast Cancer : When and H...
Marc Wigoda :  Radiotherapy of the Axilla in Early Breast Cancer : When and H...Marc Wigoda :  Radiotherapy of the Axilla in Early Breast Cancer : When and H...
Marc Wigoda : Radiotherapy of the Axilla in Early Breast Cancer : When and H...
 
Advanced&metastatic breast cancer
Advanced&metastatic breast cancerAdvanced&metastatic breast cancer
Advanced&metastatic breast cancer
 
Post mastectomy Radiotherapy with trails
Post mastectomy Radiotherapy with trailsPost mastectomy Radiotherapy with trails
Post mastectomy Radiotherapy with trails
 
Surgical persrective in lung cancer
Surgical persrective in lung cancerSurgical persrective in lung cancer
Surgical persrective in lung cancer
 
Small cell lung cancer staging and management
Small cell lung cancer staging and  managementSmall cell lung cancer staging and  management
Small cell lung cancer staging and management
 
Radiotherapy In Carcinoma Of The Breast
Radiotherapy In Carcinoma Of The BreastRadiotherapy In Carcinoma Of The Breast
Radiotherapy In Carcinoma Of The Breast
 
Sant Gallent y ESMO 2019
Sant Gallent y ESMO 2019Sant Gallent y ESMO 2019
Sant Gallent y ESMO 2019
 
Updates in Radiotherapy for Breast Cancer
Updates in Radiotherapy for Breast CancerUpdates in Radiotherapy for Breast Cancer
Updates in Radiotherapy for Breast Cancer
 
Seminoma 2012
Seminoma  2012Seminoma  2012
Seminoma 2012
 
MELANOMA.pptx
MELANOMA.pptxMELANOMA.pptx
MELANOMA.pptx
 
Ca Cervix Dr Naresh Jakhotia
Ca Cervix Dr Naresh JakhotiaCa Cervix Dr Naresh Jakhotia
Ca Cervix Dr Naresh Jakhotia
 
Nasopharynx
Nasopharynx Nasopharynx
Nasopharynx
 
ADJUTANT RADIOTHERAPY IN BREAST CANCER
ADJUTANT RADIOTHERAPY IN BREAST CANCER ADJUTANT RADIOTHERAPY IN BREAST CANCER
ADJUTANT RADIOTHERAPY IN BREAST CANCER
 
Part ii management of testicular carcinoma - dr vandana
Part ii   management of testicular carcinoma - dr vandanaPart ii   management of testicular carcinoma - dr vandana
Part ii management of testicular carcinoma - dr vandana
 
BALKAN MCO 2011 - E. Vrdoljak - Radiotherapy
BALKAN MCO 2011 - E. Vrdoljak - RadiotherapyBALKAN MCO 2011 - E. Vrdoljak - Radiotherapy
BALKAN MCO 2011 - E. Vrdoljak - Radiotherapy
 
BALKAN MCO 2011 - A. Eniu - How to optimize systemic therapy in LABC
BALKAN MCO 2011 - A. Eniu - How to optimize systemic therapy in LABC BALKAN MCO 2011 - A. Eniu - How to optimize systemic therapy in LABC
BALKAN MCO 2011 - A. Eniu - How to optimize systemic therapy in LABC
 
MCC 2011 - Slide 11
MCC 2011 - Slide 11MCC 2011 - Slide 11
MCC 2011 - Slide 11
 
Management Of Early Stage Ca Cervix [Autosaved]
Management Of Early Stage Ca Cervix [Autosaved]Management Of Early Stage Ca Cervix [Autosaved]
Management Of Early Stage Ca Cervix [Autosaved]
 
BALKAN MCO 2011 - J. Zgajnar and M. Margaritoni - Surgery (SLNB, management o...
BALKAN MCO 2011 - J. Zgajnar and M. Margaritoni - Surgery (SLNB, management o...BALKAN MCO 2011 - J. Zgajnar and M. Margaritoni - Surgery (SLNB, management o...
BALKAN MCO 2011 - J. Zgajnar and M. Margaritoni - Surgery (SLNB, management o...
 
Lung cancer
Lung cancerLung cancer
Lung cancer
 

Kürzlich hochgeladen

Generative AI in Health Care a scoping review and a persoanl experience.
Generative AI in Health Care a scoping review and a persoanl experience.Generative AI in Health Care a scoping review and a persoanl experience.
Generative AI in Health Care a scoping review and a persoanl experience.Vaikunthan Rajaratnam
 
Role of Soap based and synthetic or syndets bar
Role of  Soap based and synthetic or syndets barRole of  Soap based and synthetic or syndets bar
Role of Soap based and synthetic or syndets barmohitRahangdale
 
SGK ĐIỆN GIẬT ĐHYHN RẤT LÀ HAY TUYỆT VỜI.pdf
SGK ĐIỆN GIẬT ĐHYHN        RẤT LÀ HAY TUYỆT VỜI.pdfSGK ĐIỆN GIẬT ĐHYHN        RẤT LÀ HAY TUYỆT VỜI.pdf
SGK ĐIỆN GIẬT ĐHYHN RẤT LÀ HAY TUYỆT VỜI.pdfHongBiThi1
 
Unit I herbs as raw materials, biodynamic agriculture.ppt
Unit I herbs as raw materials, biodynamic agriculture.pptUnit I herbs as raw materials, biodynamic agriculture.ppt
Unit I herbs as raw materials, biodynamic agriculture.pptPradnya Wadekar
 
Breast cancer -ONCO IN MEDICAL AND SURGICAL NURSING.pptx
Breast cancer -ONCO IN MEDICAL AND SURGICAL NURSING.pptxBreast cancer -ONCO IN MEDICAL AND SURGICAL NURSING.pptx
Breast cancer -ONCO IN MEDICAL AND SURGICAL NURSING.pptxNaveenkumar267201
 
Mental health Team. Dr Senthil Thirusangu
Mental health Team. Dr Senthil ThirusanguMental health Team. Dr Senthil Thirusangu
Mental health Team. Dr Senthil Thirusangu Medical University
 
Male Infertility, Antioxidants and Beyond
Male Infertility, Antioxidants and BeyondMale Infertility, Antioxidants and Beyond
Male Infertility, Antioxidants and BeyondSujoy Dasgupta
 
AUTONOMIC NERVOUS SYSTEM organization and functions
AUTONOMIC NERVOUS SYSTEM organization and functionsAUTONOMIC NERVOUS SYSTEM organization and functions
AUTONOMIC NERVOUS SYSTEM organization and functionsMedicoseAcademics
 
blood bank management system project report
blood bank management system project reportblood bank management system project report
blood bank management system project reportNARMADAPETROLEUMGAS
 
Trustworthiness of AI based predictions Aachen 2024
Trustworthiness of AI based predictions Aachen 2024Trustworthiness of AI based predictions Aachen 2024
Trustworthiness of AI based predictions Aachen 2024EwoutSteyerberg1
 
"Radical excision of DIE in subferile women with deep infiltrating endometrio...
"Radical excision of DIE in subferile women with deep infiltrating endometrio..."Radical excision of DIE in subferile women with deep infiltrating endometrio...
"Radical excision of DIE in subferile women with deep infiltrating endometrio...Sujoy Dasgupta
 
CONNECTIVE TISSUE (ANATOMY AND PHYSIOLOGY).pdf
CONNECTIVE TISSUE (ANATOMY AND PHYSIOLOGY).pdfCONNECTIVE TISSUE (ANATOMY AND PHYSIOLOGY).pdf
CONNECTIVE TISSUE (ANATOMY AND PHYSIOLOGY).pdfDolisha Warbi
 
FDMA FLAP - The first dorsal metacarpal artery (FDMA) flap is used mainly for...
FDMA FLAP - The first dorsal metacarpal artery (FDMA) flap is used mainly for...FDMA FLAP - The first dorsal metacarpal artery (FDMA) flap is used mainly for...
FDMA FLAP - The first dorsal metacarpal artery (FDMA) flap is used mainly for...Shubhanshu Gaurav
 
AORTIC DISSECTION and management of aortic dissection
AORTIC DISSECTION and management of aortic dissectionAORTIC DISSECTION and management of aortic dissection
AORTIC DISSECTION and management of aortic dissectiondrhanifmohdali
 
Male Infertility Panel Discussion by Dr Sujoy Dasgupta
Male Infertility Panel Discussion by Dr Sujoy DasguptaMale Infertility Panel Discussion by Dr Sujoy Dasgupta
Male Infertility Panel Discussion by Dr Sujoy DasguptaSujoy Dasgupta
 
SGK RỐI LOẠN TOAN KIỀM ĐHYHN RẤT HAY VÀ ĐẶC SẮC.pdf
SGK RỐI LOẠN TOAN KIỀM ĐHYHN RẤT HAY VÀ ĐẶC SẮC.pdfSGK RỐI LOẠN TOAN KIỀM ĐHYHN RẤT HAY VÀ ĐẶC SẮC.pdf
SGK RỐI LOẠN TOAN KIỀM ĐHYHN RẤT HAY VÀ ĐẶC SẮC.pdfHongBiThi1
 
SGK LEUKEMIA KINH DÒNG BẠCH CÂU HẠT HAY.pdf
SGK LEUKEMIA KINH DÒNG BẠCH CÂU HẠT HAY.pdfSGK LEUKEMIA KINH DÒNG BẠCH CÂU HẠT HAY.pdf
SGK LEUKEMIA KINH DÒNG BẠCH CÂU HẠT HAY.pdfHongBiThi1
 

Kürzlich hochgeladen (20)

Generative AI in Health Care a scoping review and a persoanl experience.
Generative AI in Health Care a scoping review and a persoanl experience.Generative AI in Health Care a scoping review and a persoanl experience.
Generative AI in Health Care a scoping review and a persoanl experience.
 
Role of Soap based and synthetic or syndets bar
Role of  Soap based and synthetic or syndets barRole of  Soap based and synthetic or syndets bar
Role of Soap based and synthetic or syndets bar
 
Rheumatoid arthritis Part 1, case based approach with application of the late...
Rheumatoid arthritis Part 1, case based approach with application of the late...Rheumatoid arthritis Part 1, case based approach with application of the late...
Rheumatoid arthritis Part 1, case based approach with application of the late...
 
SGK ĐIỆN GIẬT ĐHYHN RẤT LÀ HAY TUYỆT VỜI.pdf
SGK ĐIỆN GIẬT ĐHYHN        RẤT LÀ HAY TUYỆT VỜI.pdfSGK ĐIỆN GIẬT ĐHYHN        RẤT LÀ HAY TUYỆT VỜI.pdf
SGK ĐIỆN GIẬT ĐHYHN RẤT LÀ HAY TUYỆT VỜI.pdf
 
Unit I herbs as raw materials, biodynamic agriculture.ppt
Unit I herbs as raw materials, biodynamic agriculture.pptUnit I herbs as raw materials, biodynamic agriculture.ppt
Unit I herbs as raw materials, biodynamic agriculture.ppt
 
Breast cancer -ONCO IN MEDICAL AND SURGICAL NURSING.pptx
Breast cancer -ONCO IN MEDICAL AND SURGICAL NURSING.pptxBreast cancer -ONCO IN MEDICAL AND SURGICAL NURSING.pptx
Breast cancer -ONCO IN MEDICAL AND SURGICAL NURSING.pptx
 
Mental health Team. Dr Senthil Thirusangu
Mental health Team. Dr Senthil ThirusanguMental health Team. Dr Senthil Thirusangu
Mental health Team. Dr Senthil Thirusangu
 
Male Infertility, Antioxidants and Beyond
Male Infertility, Antioxidants and BeyondMale Infertility, Antioxidants and Beyond
Male Infertility, Antioxidants and Beyond
 
American College of physicians ACP high value care recommendations in rheumat...
American College of physicians ACP high value care recommendations in rheumat...American College of physicians ACP high value care recommendations in rheumat...
American College of physicians ACP high value care recommendations in rheumat...
 
AUTONOMIC NERVOUS SYSTEM organization and functions
AUTONOMIC NERVOUS SYSTEM organization and functionsAUTONOMIC NERVOUS SYSTEM organization and functions
AUTONOMIC NERVOUS SYSTEM organization and functions
 
blood bank management system project report
blood bank management system project reportblood bank management system project report
blood bank management system project report
 
Trustworthiness of AI based predictions Aachen 2024
Trustworthiness of AI based predictions Aachen 2024Trustworthiness of AI based predictions Aachen 2024
Trustworthiness of AI based predictions Aachen 2024
 
"Radical excision of DIE in subferile women with deep infiltrating endometrio...
"Radical excision of DIE in subferile women with deep infiltrating endometrio..."Radical excision of DIE in subferile women with deep infiltrating endometrio...
"Radical excision of DIE in subferile women with deep infiltrating endometrio...
 
CONNECTIVE TISSUE (ANATOMY AND PHYSIOLOGY).pdf
CONNECTIVE TISSUE (ANATOMY AND PHYSIOLOGY).pdfCONNECTIVE TISSUE (ANATOMY AND PHYSIOLOGY).pdf
CONNECTIVE TISSUE (ANATOMY AND PHYSIOLOGY).pdf
 
Immune labs basics part 1 acute phase reactants ESR, CRP Ahmed Yehia Ismaeel,...
Immune labs basics part 1 acute phase reactants ESR, CRP Ahmed Yehia Ismaeel,...Immune labs basics part 1 acute phase reactants ESR, CRP Ahmed Yehia Ismaeel,...
Immune labs basics part 1 acute phase reactants ESR, CRP Ahmed Yehia Ismaeel,...
 
FDMA FLAP - The first dorsal metacarpal artery (FDMA) flap is used mainly for...
FDMA FLAP - The first dorsal metacarpal artery (FDMA) flap is used mainly for...FDMA FLAP - The first dorsal metacarpal artery (FDMA) flap is used mainly for...
FDMA FLAP - The first dorsal metacarpal artery (FDMA) flap is used mainly for...
 
AORTIC DISSECTION and management of aortic dissection
AORTIC DISSECTION and management of aortic dissectionAORTIC DISSECTION and management of aortic dissection
AORTIC DISSECTION and management of aortic dissection
 
Male Infertility Panel Discussion by Dr Sujoy Dasgupta
Male Infertility Panel Discussion by Dr Sujoy DasguptaMale Infertility Panel Discussion by Dr Sujoy Dasgupta
Male Infertility Panel Discussion by Dr Sujoy Dasgupta
 
SGK RỐI LOẠN TOAN KIỀM ĐHYHN RẤT HAY VÀ ĐẶC SẮC.pdf
SGK RỐI LOẠN TOAN KIỀM ĐHYHN RẤT HAY VÀ ĐẶC SẮC.pdfSGK RỐI LOẠN TOAN KIỀM ĐHYHN RẤT HAY VÀ ĐẶC SẮC.pdf
SGK RỐI LOẠN TOAN KIỀM ĐHYHN RẤT HAY VÀ ĐẶC SẮC.pdf
 
SGK LEUKEMIA KINH DÒNG BẠCH CÂU HẠT HAY.pdf
SGK LEUKEMIA KINH DÒNG BẠCH CÂU HẠT HAY.pdfSGK LEUKEMIA KINH DÒNG BẠCH CÂU HẠT HAY.pdf
SGK LEUKEMIA KINH DÒNG BẠCH CÂU HẠT HAY.pdf
 

management of early breast cancer

  • 1. ModeratorModerator Dr Haresh K.PDr Haresh K.P Department of RadiotherapyDepartment of Radiotherapy AIIMS, NEW DELHIAIIMS, NEW DELHI MANAGEMENT OF EARLY STAGEMANAGEMENT OF EARLY STAGE BREAST CARCINOMABREAST CARCINOMA Speaker Dr Ruchir Bhandari
  • 2. 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
  • 3. Evolution Of Treatment Extended Radical MRM MRMBCS LRRTWBRTAPBILRRTWBRTAPBI ChemotherapyHormonal TherapyBiological Therapy OncotypeDx/Mammaprint/ rotterdam Signature/PAM50 OncotypeDx/Mammaprint/ rotterdam Signature/PAM50 QOL Psychosocial Outcome
  • 4. TYPES OF SURGERY Simple mastectomy Extended RadicalExtended Radical mastectomymastectomy
  • 5. 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 biopsyExcision biopsy Do MRM if 1.Large tumors in small breast 2. EIC 3. –ve margin not attained 4. Diffuse micro calcifications 5. Cx of RT 6. Pt unreliable for f/u.
  • 6. 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 / WLE Local fat mobilization Mini LD flap Extended LD flap  After mastectomy Vertical / transverse rectus abdominis flap Gluteal free flap
  • 7. 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%
  • 8. Axillary dissectionAxillary dissection  Axillary nodal status determines  adj. CT  level I & II ; 10 is minimum cN0  20 - 40 % pN0 cN+  20 - 40 % pNO  Skip mets to level II – 15% , level III – 1-3%  Level III dissection  cN+, skin +  Lymphoedema (3-5%  10-15%) Absolute benefit of 5.4% Orr et al, 1999
  • 9. Sentinel lymph node biopsySentinel 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
  • 10. 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
  • 11. 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?
  • 13. 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%
  • 14. 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 women FNR 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
  • 15. SLNB - ASCO 14 recommendations SLNB controversial for multi-centric disease, Post NACT, prior RT or SX
  • 16. BCS vs Mastectomy Veronesi et al: NEJM 2002 IS SURGERY THE ONLY TREATMENT ?
  • 17. BCS vs Mastectomy Veronesi et al: NEJM 2002
  • 18. 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 “
  • 19. Prospective Randomized Trials of Lumpectomy +/- Radiotherapy Necessity for Radiation Therapy (In Early Stage Breast Cancer)…… No subset of patients, where RT can be omitted
  • 20. AbsoluteAbsolute 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 RelativeRelative 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
  • 21. RADIOTHERAPYRADIOTHERAPY Aims – 1. To decrease chances of LR ; treats microscopic ds 2. Increase local control & hence increase survival Postop RT - mastectomy - lumpectomy Indications - 1. Tumor – >5cm , LVE + , gr2 / 3 , skin/ ms infiltr , EIC 2. Lymph nodes – number, ECE, inadequate ALND 3. Surgery – margins +ve , unknown or close 4. Patient – age <35yrs , premenopausal
  • 22. 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%
  • 23. Adjuvant RT after Mastectomy
  • 24. Adjuvant RT after BCS Stratification for Radiotherapy
  • 25. 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
  • 26. 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
  • 27. 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
  • 28. 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
  • 29. 1. Electrons – @ 85 -90% isodose line ; 9-16 MeV ; 10-20Gy Set up - post lumpectomy volume or scar +2 cm in all directions 2. Interstitial 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 uncertainties : patients, clips and cavity position BOOST TO TUMOR BED
  • 30. Boost ComplicationsBoost Complications Criticism  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%
  • 31. 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
  • 32. 3232 Better Local Control with RT Boost Acta Oncologica 2007; 46:879 - 892 2657 2661
  • 33. Current issues in radiation therapy  Treatment Volume: Whole breast or Partial breast irradiation Internal 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
  • 34. 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
  • 35. APBI : AdvantagesAPBI : Advantages  Improves underutilization of BCT  Avoids prolonged Rx regimens, more acceptable  Reduces time, cost and inconvenience  Improves QOL & Reduces acute & chronic toxicity  Eliminates scheduling problems with CT / HT
  • 36. Selection criteria 1 Arthur, et al. Accelerated partial breast irradiation: an updated report from the American Brachytherapy Society. Brachytherapy, 1:184-190, 2003. 2 Consensus statement for accelerated partial breast irradiation. The American Society of Breast Surgeons. April 30, 2003.
  • 37. Consensus Guidelines: ASTRO Smith et aI Int. J. Radiation Oncology Biol. Phys 2009,74(4): 987–1001
  • 38. 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
  • 41. 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
  • 42. 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 • 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 R A N D O M I Z A T I O N R A N D O M I Z A T I O N 50 Gy/25#/5 weeks50 Gy/25#/5 weeks 41.6Gy/13#/5 weeks41.6Gy/13#/5 weeks 39 Gy/13#/5 weeks39 Gy/13#/5 weeks 14% received LRRT BOOST- 10Gy 61% received BOOST 14% received LRRT BOOST- 10Gy 61% received BOOST The principal end points: local-regional relapse, normal tissue effects, and quality of life
  • 43. 04/06/15 AIIMS 43 START B Trial •N=2215 •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=2215 •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 R A N D O M I Z A T I O N R A N D O M I Z A T I O N 50 Gy/25#/5 weeks50 Gy/25#/5 weeks 40Gy/15#/3 weeks40Gy/15#/3 weeks 14% received LRRT BOOST- 10Gy 14% received LRRT BOOST- 10Gy The principal end points: local-regional relapse, normal tissue effects, and quality of life 43% received BOOST43% received BOOST
  • 44. Loco-regional recurrence is not different in the 50 Gy and 40 Gy arm
  • 45. Disease free Survival Disease free survival is not different in the 50 Gy and 40 Gy arm
  • 46. 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
  • 47. ASTRO guidelines for fractionation Int. J. Radiation Oncology Biol. Phys.; 81(1):59–68, 2011 IMPORT High IMPORT Low 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) vs 2.67 x 15 (+16 Gy seq. boost) 2.67 x 15 WB vs 2.4 x 15 WB + Conc. Boost vs 2.67 x 15 APBI 2 x 25 WB + 2 x 8 seq vs 2.67 x 15 WB vs APBI 4 x 10 2 x 25 + seq boost VS 2.67 x 15 + conc. Boost
  • 48. No Consensus on the use of PMRT 1-3 LN +ve Pts. Uncertain : NIH Consensus Statement 2000 ASCO Guidelines, JCO 2001 ACR 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) [ 8th WCI-TMH ] 10yr LRR in 1-3 LN +ve M D Anderson: 12% ECOG: 13% NSABP: 6-11% IBCSG : 14-27%
  • 49. 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
  • 50. 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
  • 51. 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
  • 52. Adjuvant systemic therapy : Why requiredAdjuvant 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
  • 53. IndicationsIndications  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
  • 54. Progress in Chemotherapy for Early StageProgress 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
  • 55. 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
  • 57. GENOMIC PROFILING early breast cancer, N- , ER+ve, Her2 –ve 1.Oncotype Dx -- 21 gene signature, RT-PCR on21 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- andFresh 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 genes 4.4. Rotterdam 76 gene signatureRotterdam 76 gene signature 5. Genomic grade index5. Genomic grade index 6. Breast cancer index6. Breast cancer index RXpONDER Trial – evaluating benfit in 1-3 node+ disease ERA OF PERSONALISED MEDICINE
  • 58. 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
  • 59. Hormonal management – A balance Fracture fatigue Hot flush Hot flush Endometrial carcinoma Thrombo-embolism Aromatase Inhibitors Non-Steroidal Anastrozole Letrozole Steroidal Exemestane Tamoxifen ATAC- No OS benefit BIG 1-98- 4% OS benifit IES 2.1% OS benefit ARNO-95- 2.3% OS benifit ATAC- No OS benefit BIG 1-98- 4% OS benifit IES 2.1% OS benefit ARNO-95- 2.3% OS benifit Switch /Mono-therapy
  • 60. 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
  • 61. 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
  • 62. 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
  • 63. Effect of anastrozole and tamoxifen as adjuvant treatment for 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
  • 64. 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
  • 65. ATLAS Trial aTTOM Trial OPTIMAL DURATION OF TAMOXIFEN TREATMENT ?
  • 66. Hormonal Management Adjuvant treatment - In ER+/PR+, her2neu3+/-treatment options ASCO, JCO,2014
  • 67. 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.
  • 68. 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.
  • 69. Study design- Bolero II R A N D O M I Z A T I O N •multicenter, •open-label •phase III study •N=724 •Randomization 2:1 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 response rate, clinical benefit rate, time to deterioration of ECOG performance status, safety, and quality of life • The primary end point PFS • Secondary end points: overall survival, overall response rate, clinical benefit rate, time to deterioration of 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
  • 70. AIIMS
  • 71. 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
  • 72. Trastuzumab significantly reduces the risk of recurrence and prolongs OS Concurrent 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%).

Hinweis der Redaktion

  1. Methylene blue and 99 m-Technetium (99-Tc) – safe in pregnancy ( NCCN 2011) but ASCO recommends against it
  2. QOL items in the arm symptom scale: swelling (ART better) and movement (ALND better)
  3. Boost field: tumor site + 1.5 cm if “completely excised” (3 cm if not)
  4. percutaneous electron boost Reduces tte risk for recurrence from 7.3 % to 4.3 % after 5 years often initiated with a delay of several months after surgery causing higher recurrence rate It fails to hit the exact former location of the tumor in 50 - 80% of patients(e.g. Benda RK et al., Cancer 2003; 97:905)
  5. Purpose: To examine the power of the nodal ratio (NR) of positive/excised nodes in predicting postmastectomy locoregional recurrence (LRR) in patients with 1–3 positive nodes (N) and in identifying cohorts at similar risk across independent data sets. Methods and Materials: Data from 82 patients with 1–3 N treated without postmastectomy radiotherapy (PMRT) in the British Columbia (BC) randomized trial were compared with data from 462 patients treated without PMRT in prospective chemotherapy trials at the M. D. Anderson Cancer Center (MDACC). Kaplan- Meier LRR curves were compared between centers using the absolute number of N and nodal ratios. Results: The median number of excised nodes was 10 in BC and 16 in MDACC (p &amp;lt; 0.001). Examining LRR by number of N, the 10-year LRR rate for patients with 1–3 N was higher in BC compared with MDACC (21.5% vs. 12.6%; p 0.02). However, when examining LRR using NR, no differences were found between institutions. In patients with NR &amp;lt; 0.20, the 10-year LRR rate was 17.7% BC vs. 10.9% MDACC (p 0.27). In patients with NR &amp;gt; 0.20, the 10-year LRR rate was 28.7% BC vs. 22.7% MDACC (p 0.32). On Cox regression analysis, NR was a stronger prognostic factor compared with number of N . Conclusions: In patients with 1–3 N, evaluating nodal positivity using NR reduced inter-institutional differences in LRR estimates that may exist due to variations in numbers of nodes excised. Nodal ratio &amp;gt;0.20 was associated with LRR &amp;gt;20%, warranting PMRT consideration. Nodal ratio may be useful for extrapolating data from prospective trials to clinical practices in which axillary staging extent vary. © 2007 Elsevier Inc.
  6. Side effects Hot flashes Vaginal dryness, discharge Risk of endometrial cancer Increased TE events Cataracts
  7. However timing and duration of switch remain to be established. Use in premenopausal women not recommended. Whether AI &amp;gt; 5yrsis beneficial ?? NSABP 42 &amp; NCIC-MA 17R Trial ongoing
  8. Scottish Cancer Trials Breast Group and ICRF Breast Unit GsH, London. Adjuvant ovarian ablation versus CMF chemotherapy in premenopausal women with pathological stage II breast carcinoma: the Scottish trial. Lancet 1993;341:1293–1298. Jonat W, Kaufmann M, Sauerbrei W, et al. Goserelin versus cyclophosphamide, methotrexate, and fluorouracil as adjuvant therapy in premenopausal patients with node-positive breast cancer: the Zoladex Early Breast Cancer Research Association Study. J Clin Oncol 2002;20:4628–4635.