35 th sabcs 2012 highlights loco-regional therapy
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35 th SABCS 2012 Highlights Loco-Regional Therapy. Patrick Neven MBC, UZ Leuven. 35th SABCS 2012 Loco-Regional Therapy. Atypical lesions on core biopsy WLE? Upgrade to malignant lesions (frequency, nomogram) WLE for DCIS Re-excise if + margins (predictors residual DCIS) - PowerPoint PPT PresentationTRANSCRIPT
35th SABCS 2012 Highlights
Loco-Regional Therapy
Patrick NevenPatrick Neven
MBC, UZ LeuvenMBC, UZ Leuven
35th SABCS 2012 Loco-Regional Therapy
– Atypical lesions on core biopsyWLE?• Upgrade to malignant lesions (frequency, nomogram)
– WLE for DCIS• Re-excise if + margins (predictors residual DCIS)• Predictors relapse (subtype, gene expression profile)
– WLE for IBC • Tumor localisation, 2nd WLE
– Sentinel lymph node• Value in post-neoadjuvant setting
– Radiotherapy• START (hypofractionation)• APBI – IORT/ELIOT
– Local relapse: Secondary adjuvant chemotherapy
35th SABCS 2012 Loco-Regional Therapy
– Atypical lesions on core biopsyWLE?• Upgrade to malignant lesions (frequency, nomogram)
– Flat epithelial atypia on core biopsy• Loyola, USA (P1-02-01) 2009-2011 726 core biopsies
– 21.4% (3/14) upgraded to DCIS or IBC
• 3 Dutch hospitals (P5-01-13) 2009-2011 104 core biopsies– R/ ranged from observation to mastectomy
– Of those excised: 20.4% had DCIS or IBC
– ADH on vacuum biopsy • Centre Oscar Lambret, Lille (P4-14-10) 2003-2010
– 52/298 WE/3159 VAB = 17.5% had DCIS or IBC
– No prognostic marker identified for upstaging
WLE if atypical lesions on core biopsy?
Wide Excision = StandardMESSAGE
A nomogram ~ clinic, imaging & histologyto predict upgrade to malignancy (WLE)
LCIS, ADH, ALH, FEA (core biopsyP4-12-01 Uzan et al.
50/205WLE-21 DCIS-20 IDA -9 ILA
Sens 77.8%, Sp 66.1%, PPV 40%, NPV 91.1%
35th SABCS 2012 Loco-Regional Therapy
– Atypical lesions on core biopsyWLE?• Upgrade to malignant lesions (frequency, nomogram)
– WLE for DCIS• Residual DCIS if re-excision for + margins• Predictors for relapse (~ subtype, gene expression profile)
– Ki-67 (continuous variable) ~LRR after BCS & RT & HT?
» PD-04-07 – Pruneri et al. EIO, Milan
» 872 pts, [356 RT, 506 TAM] and 86/12 FU
» RT only of value if Ki-67 > 14%» HT only of value if lum A/B (not lum HER-2)
MESSAGE
Residual DCIS after re-excision following WLE for DCIS?
• IBC: Margin index predicts residual cancer• P3-14-06 – AS Aneja S. et al.
– 177 pts and 87 re-excision (18 rDCIS)• Index: closest margin (mm)/ extent of DCIS (mm)
– Index > margin distance
– PR most predictiveMESSAGE
Local Relapse after BCS (DCIS)• Surrogate phenotypes ~ recurrence (PD-04-06)
– 314 pts (1990 – 2010) 74 months FU
– Radiotherapy? High risk recurrence?
Luminal A 1 - -Luminal B 14.38 1.8-113.6 0.011HER-2 type 17.69 2.1-147.0 0.008Triple Negative 15.23 1.8-126.6 0.012
Predictors for IBC if relapse
Molecular predictors type LR: after BCS for DCIS PD-04-05
• Local relapse DCIS vs IBC +/- DCIS – 1991-2006, 1873 pts, 40m FU, 190 relapsed (10%), 108 blocks:
66 rDCIS & 42 rIBC qmRNA– Quantification of mRNA done by Nanostring nCounter system– 32 BC-related genes selected from literature (why these and not others?)
• HER-2;PI3K/AKT; genes involved in proliferation/recurrence
– Initial unsupervised hierarchical clustering:» 2 groups: rDCIS & rIBC enriched
– 14 genes w/ sig differential expression:» rDCIS “only” : highest levels of AKT3, EGFR, CDKN2A, MKI67,
typical of basal like tumors
Molecular predictors type LRR: after BCS for DCIS
Molecular Predictor LRR BCS for DCIS
35th SABCS 2012 Loco-Regional Therapy
– Atypical lesions on core biopsyWLE?• Upgrade to malignant lesions (frequency, nomogram)
– WLE for DCIS• Re-excise if + margins (predictors residual DCIS)• Predictors relapse (subtype, gene expression profile)
– WLE for IBC • Tumor localisation• 2nd WLE
IBC: Breast conservation surgery
• Patient selection– BCS rates in SEER (PD-04-04)
• Stage I-II IBC 2006-2011: 77248 cases BCS: 64.8% & stable• Patients choice > Availability RT/Reconstr/Volume per Unit
– BCS in young women (Sydney)(PD-04-01)• N=2250 & 70/12 FU: Age <40 & BCS indep.predictors for LR
• Technique– Intraoperative ultrasound (PD-04-01)
• P4-14-08 278 not-palpable lesions USS vs wire guided = feasible
– 2ary WLE in irradiated breast (P4-15-01)
BCS: Role of intraoperative ultrasound (IOUS) palpable lesions
• PD-04-01: RCT USS (65) vs PGS (69)• 2010-2012, 6 centers, T1-2 palp IBC
Less volume excised in USS
Less margin involved 17% vs 3% USS
Less likely additional therapy
Margin definition???
Patients with IBTR: 2ary BCS?
• Second BCS-RT trial (P4-15-01) GEC-ESTRO• Patients from 8 European Institutions: • WLE + MIB (Multicatheter Interstitial Brachytherapy)
– Is 2ary BCT safe for IBTR?• 2000-2010: 217 pts repeat BCS + MIB. • Median time interval Primary – IBTR = 9.4 yrs [1.1-35.4]
• Median f/u after IBTR = 3.9 years [after 2ary BCS].• Mean T = 11mm• Median RT dose for primary was 56 Gy [30-69.6]
• 5 and 10 year actuarial – LR rates 5.6% and 7.2%– OSS 88.7% and 76.4%
• No severe complications but fibrosis.• Long term cosmesis? Clinical
PracticeChanging
35th SABCS 2012 Loco-Regional Therapy
– Atypical lesions on core biopsyWLE?• Upgrade to malignant lesions (frequency, nomogram)
– WLE for DCIS• Re-excise if + margins (predictors residual DCIS)• Predictors relapse (subtype, gene expression profile)
– WLE for IBC • Tumor localisation, 2nd WLE
– Sentinel lymph node• Value in post-neoadjuvant setting
SLN Biopsy after Neoadjuvant Chemotherapy
–S2-1 (ACOSOG)
–S2-2 (SENTINA trial)
Background
SLNB ~ axillary status if cN0-pN status tailors L/R adjuvant therapy
Role of SLNB with NACT is unclear-cN0: prior to but after NACT if pN status not informative?
-cN+: downstaging to cN0 (no ALND)???-current data
-small series-retrospective data
SLN Biopsy after Neoadjuvant Chemotherapy
–S2-1 (ACOSOG)
–S2-2 (SENTINA trial)
Sentinel Node Biopsy after NAC
ACOSOG Z-0171 (2009-2011)• pT0-4N1-2M0: NAC SN and ALND (136 institutions)
– T1 (14%); T2 (55%); T3 (25%)» HR+/Her2- (45%); » Her2+ (30%); » Trip neg (24%);
• Anthracycline +/- taxane (80%), taxane based (17%)
– SN detection rate• cN1 (92.9%), cN2 (89.5%) : SLN ALND (n=643)
– SN H&E results SNALND• 40% node negative• 60% node positive
– SN negative 56 patients (14%)
756 included708 evaluable
FNR: 14.0% Clip Placement ?
172 pts FNR = 7%
- 4-arm prospective multicenter cohort study- SLN detection rate prior and after NACT- FNR if cN1 downgraded to cN0- cN1: clinic and all had US
- Negative (cN0)- Suspicious or unclear (cN1)
- FNAC/ CNB recommended but not mandatoryCortex asymmetry
- Hilum displacement or loss
SENTINA
cN+ definitionFNAC/CNB Not Mandatory
↔cN0: SLN after NACT: Accurate/ Feasible
Less Axill Clearance
Sentinel Lymph Node
Prior to NACT (~local and systemic R/)
Excellent Detection Rate (DR)After NACT
cN0ycN0: Excellent DRcN0 & SN(+)Repeat SLN = Unacceptable DR
cN1 ycN0 DR is 80.1% = LowFNR = Too High?
35th SABCS 2012 Loco-Regional Therapy
– Atypical lesions on core biopsyWLE?• Upgrade to malignant lesions (frequency, nomogram)
– WLE for DCIS• Re-excise if + margins (predictors residual DCIS)• Predictors relapse (subtype, gene expression profile)
– WLE for IBC • Tumor localisation, 2nd WLE
– Sentinel lymph node• Value in post-neoadjuvant setting
– Radiotherapy• START (hypofractionation)• APBI – IORT (TARGIT- ELIOT)
Content
Hypofractionation (= less than 25 fractions)•[S4-1] The UK START (Standardisation of Breast Radiotherapy) Trials: 10-Year Follow-Up Results
APBI: Single Fraction RT•[S4-2] Targeted Intraoperative Radiotherapy for Early Breast Cancer: TARGIT-A Trial- Updated Analysis of Local Recurrence and First Analysis of Survival
•[P4-16-08] Intraoperative Electron Radiotherapy in Early Stage Breast Cancer. A Single-Institution Experience ELIOT
Local control if metastatic breast cancer •[P4-16-06] RT to Primary Tumor ~ Improved Survival in Stage IV Breast Cancer (Canadia, SEER, 768 cases EBRT vs 2761 no EBRT)
Best of SABCS 2012
Radiation Oncology
Normal a total dose 50Gy in 25 small daily fractions (5 weeks)
Hypofractionated Breast RT
Change in DOSE:
*Hypofractionatedlarger dose per fraction
*Same time vs. shorter time
versus
versus
Findings
START B: Physicians’ assessment of cosmesis
Clinical Practice
Changing
APBI• Single fraction IORT
– S 4-2 TARGIT for early stage breast cancer• TARGIT vs WB-XRT
– TARGIT “ideal” pt age ≥ 45; T preferably ≤ 3.5 cm; MRI no need
» TARGIT 20 Gy at surface, 5 Gy at 10 mm
» If “high risk” add WB-XRT to single-fraction IORT (~ 15%)
– 2000-2012: 3451 pts randomized, 1222 patients median f/u 5 yrs
ELIOT
TARGIT
APBI
TARGIT0.5% LRR/YR“EXPERIMENTAL”
• Single fraction IORT– Verona experience, phase II single fraction
IORT with IOERT (P4-16-08)
– 2006-2009, 226 pts, “low risk”, early stage IBC• Age > 50; T < 3 cm, G1-3, unifocal IDC. No DCIS,
EIC, or ILC
• 21 Gy to tumor bed with 2 cm margins laterally
• Mean f/u 51 months, 4 IBTR
IORT Following Lumpectomy for Breast Cancer Sem Br Dis Dirbas FM, Horst KC 2007
35th SABCS 2012 Loco-Regional Therapy
– Atypical lesions on core biopsyWLE?• Upgrade to malignant lesions (frequency, nomogram)
– WLE for DCIS• Re-excise if + margins (predictors residual DCIS)• Predictors relapse (subtype, gene expression profile)
– WLE for IBC • Tumor localisation, 2nd WLE
– Sentinel lymph node• Value in post-neoadjuvant setting
– Radiotherapy• TARGIT (hypofractionation)• APBI - IORT
– Local relapse: Secondary adjuvant chemotherapy Clinical Practice
Changing↓ →
Ipsilateral recurrence: Value of Secundary Adj CTPower calculation : needed to include: n= 1000…results from a RCT that stopped early: poor recruitementThe researchers closed the trial with 162 patients Followed patients for more than 5 years.Stratified by ER
Summary 35th SABCS-2012 LOCO-REGIONAL THERAPY
• Atypical breast lesions : WLE still recommended • Research efforts will continue to identify biological markers to
inform need for re-excision and adjuvant local / endocrine therapies for DCIS (and IBC)
• SNB after NACT if cN+ needs further research– high FNR requires resection of nodes with proven disease: dual tracer
and/or localization of clipped nodes. – repeat SNB alone to be avoided if cN+
• Hypofractionation is new standard after BCS (10 yrs safe)• Single fraction IORT may be equivalent to WB-XRT in select
patient subsets but higher recurrence rates in unselected patients: longer f/u required to determine if these results are sustainable and effect on CV-risk
• Secondary WLE in previously radiated breast
• Secondary adjuvant chemotherapy is important