SABCS 2012
SURGERY HIGHLIGHTS
Frederick M. Dirbas, M.D.
Associate Prof Surgery, Physician Leader Breast Clinical Cancer Program
Stanford Cancer Institute
FIBRO-EPITHELIAL TUMORS
•
Phyllodes tumors of the breast: what predicts recurrence? (P4-14-14)
• Retrospective analysis (1987-2010), 87 patients, median age 47, mean size 46.6 mm
Benign
Borderline
Malignant
No. pts
60 (69%)
10 (11.5%)
17 (19.5%)
Median age
45
45
55
BCS/Mast
66/2 (97%)
11/6 (65%)
RT
0
2
IBTR
6 (8.6%)
5 (29.4%)
Metastases
0
2 (followed IBTR) (18.2%)
Time to mets
-
-
2.5 yrs
Relapse free
91.7%
90%
70.6%
FIBRO-EPITHELIAL TUMORS
•
Phyllodes tumors of the breast: what predicts recurrence? (P4-14-14)
ATYPICAL EPITHELIAL LESIONS AND EXCISION
•
Is surgical excision warranted for atypical lesions found on core biopsy?
• Flat epithelial atypia – Loyola (P1-02-01)
• 2009-2011, 14 patients. 3 pts (21.4%) upgraded to DCIS or IBC on excision
• Flat epithelial atypia – 3 Dutch hospitals (P5-01-13)
• 2004-2011, 104 pts, treated ranged from observation to mastectomy
• Of those excised, 20.4% had DCIS or invasive breast cancer
• ADH on vacuum biopsy - Oscar Lambret Center, France (P4-14-10)
• 2003 -2010, 320 pts with excision, 17.5% upstaged to DCIS or IBC
• Grade 1 DCIS (32.6%), Grade 2 DCIS (34.6%), IBC (4.7%)
• No prognostic marker identified for upstaging
ATYPICAL EPITHELIAL LESIONS AND EXCISION
•
Can a nomogram predict the risk of histologic upgrades for full spectrum of atypical
lesions, ADH, ALH, FEA, LCIS: when to excise? (P4-12-01) – Gustave Roussy
•
. Retrospective analysis 2004-2011, 205 patient training set
• Sens 77.8%, Sp 66.1%, PPV 40%, NPV 91.1%
CENTRAL REVIEW OF PATHOLOGY AFTER
LUMPECTOMY AND SNB FOR NONPALPABLE IBC
•
Use of expert breast pathologists to confirm diagnosis (P5-01-14) – UMC Utrecht
• 310 pts with IBC and SN bx. 24% discordance rate, 9% change in mgmt
BREAST MRI
•
2006-2011, 678 patients w staging MRI, ethnically mixed population (P4-01-11) - USC
• 141 pts (21%) had non-index lesions found
• 57 pts (8.4%) had 62 occult cancers detected (49 invasive, 9 in-situ)
BREAST MRI
•
2008-2012 155 pts with ductolobular IBC, prospectively offered breast MRI (P4-01-17)
• Increase in clinically relevant findings in 44% of patients
• More extens 25 pts (22%); addit ips foci 22 pts (19%), new contra dx 12 pts (10%)
DUCTAL CARCINOMA IN SITU
•
Utility margin index to predict residual DCIS (P3-14-06) - Yale
• 2009, 177 pts: closest margin distance (mm)/extent of DCIS (mm)
• 87 pts underwent re-excision: PR status most predictive of resid disease
DUCTAL CARCINOMA IN SITU
•
Prediction of recurrent DCIS and/or IBC after BCS for DCIS
• Use of molecular phenotypes (intrinsic subset) to predict to predict recurrence (PD 04-06) – Univ of Manchester
• 1990 – 2010, 314 pts
DUCTAL CARCINOMA IN SITU
• Use of Ki-67 in predicting LRR of DIN after RT (PD-04-07) – EIO
• 1997-2007: 1,171 consec pts, med f/u 86 months
• 872 pts BCT, 356 pts RT, 506 pts TAM
• Overall recurrence 10.7%
• RT protective if Ki67 > 14%
• RT effective overall in all groups except Lum A
DUCTAL CARCINOMA IN SITU
•
Prediction of recurrent pure DCIS vs IBC +/- DCIS (PD-04-05) – MSKCC
• 1991-2006, 1873 pts
• 190 pts recurred (10%): 108 archival blocks available (57% of recur)
• 66 recurred DCIS (61%), 42 recurred IBC (39%) (mean 40 mos)
• Initial unsupervised hierarchical clustering of 32 genes showed 2 groups:
RI + RD vs RI
• 14 genes w/ sig differential expression: 3 RI +/- RD vs 1 RD
• RD “only” recurrence had highest levels of AKT3, EGFR, CDKN2A,
MKI67, typical of basal like tumors
DUCTAL CARCINOMA IN SITU
•
Prediction of recurrent pure DCIS vs IBC +/- DCIS (PD-04-05) – MSKCC
BREAST CONSERVATION SURGERY
•
Patient selection
• Current rates of breast conservation (SEER) (PD-04-04)
• Breast conservation in young women (PD-04-01)
• Breast conservation after neoadjuvant therapy (P1-14-19)
•
Technique
• Intraoperative ultrasound (PD-04-01)
• Use of radioguided localization (ROLL) (P5-15-03)
• Radiofrequency ablation – long term results (P4-15-05)
•
Repeat breast conservation (P4-15-01)
BREAST CONSERVATION SURGERY
•
What influences rates of BCS? (SEER) (PD-04-04)
• 2006-2011, 437 breast centers: 77, 248 pts Stage 0-II, 64.2% BCS
• No change during study period towards increase/decrease BCS.
BREAST CONSERVATION SURGERY
•
Breast conservation in young women (PD-04-03) – Univ New South Wales, Au
•
1995 – 2008: 246 pts ≤ 40, 2004 pts > 40. Median f/u 70 months.
•
Conclusion: women ≤ 40 have a 52% relative risk of IBTR
BREAST CONSERVATION SURGERY
•
Breast conservation in young women (PD-04-03) – Univ New South Wales, Au
•
1995 – 2008: 246 pts ≤ 40, 2004 pts > 40
•
Conclusion: women ≤ 40 have a 52% relative risk of IBTR
BREAST CONSERVATION SURGERY
•
Breast conservation after neoadjuvant therapy in clinical stage III pts (P1-14-19) - Seoul
• 2000-2007, 166 pts BCT or M after NCT and 193 pts surgery 1st
• After NCT, 94 pts (56.6%) had M: if T ≤ 4 cm 72 pts (43.4%) had BCT. f/u 62 mos.
BREAST CONSERVATION SURGERY
•
Intraoperative ultrasound improves surgical accuracy (PD-04-01) - Netherlands
• 2010-2012, 6 medical centers, T1-T2 palpable breast tumors randomly assigned to
standard excision (PGS, 69 pts) vs intraop US guided excision (USG, 65 pts)
• 12/69 pts (17%) PGS + margins, 2/62 pts (3%) USG + margins
Google Images
BREAST CONSERVATION SURGERY
•
Cost effectiveness of ROLL vs wire guided localization (P5-15-03) – Utrecht
• Histologically non-palpable cancer
• Randomized to ROLL (162 pts) vs WGL (152 pts)
• Data on QOL, cost
• No difference in OR time
• ROLL associated with 7% increase in reoperation (27% vs 20%)
• ROLL associated with 13% increase in complications (30% vs 17%)
• QOL same
• Total costs same
Google Images
BREAST CONSERVATION SURGERY
•
Radiofrequency ablation – long term results (P4-15-05) – Kanazawa Hosital, Japan
• RFA is a promising technique for non-surgical local therapy. 95 deg C
• 2005-2012, 19 pts. T < 2 cm. 17/19 “luminal A”
• Ablated tumor sampled between 24 and 202 days
• Complete response confirmed in 8/19 pts. No clinical recurrences 60 mos f/u
BREAST CONSERVATION SURGERY
•
Repeat breast conservation (P4-15-01) GEC-ESTRO
• Is BCT safe for IBTR?
• 2000-2010, 8 European Institutions. 217 pts repeat BCS + MIB. Mean T = 11mm
• Median f/u 3.9 years after 2 nd BCS.
• 5 and 10 year actuarial LR rates 5.6% and 7.2%, resp, OSS 88.7% and 76.4%
• 141 pts/193 complications, most frequent was fibrosis. Cosmesis ex/g 85%
MASTECTOMY
•
Nipple-Areolar sparing
•
Nipple-areolar complex ischemia ASBS registry (P4-14-01)
• 33/265 mastectomies had some degree of ischemia. 11% epidermolysis; 1% debridement; .3%
surgical excision. No correlation w/ technique
•
NAS increasing per SEER (P4-14-02)
• 2005-2009, NSM. Most T < 2 cm and node -.
• Increase in frequency
•
Intraoperative biopsy: to freeze or not to freeze (P4-14-03)
• 2006-2011. 237 NSM, 179 had subareolar FS.
• 11 pos bx, 7 FN intraop. Of resected NAC, 33% had residual DCIS or IBC
• Conclusion: FS of limited utility. NAC can be resected at time of delayed recon
•
Total skin sparing in BRCA patients (P4-14-05)
• 1994-2010, 293 M in 154 pts. 70 pts BRCA +.
• 4.8% occult DCIS or IBC
• 2/70 pts had late recurrence: 1 @ 3yrs (non-NSM); 1 @ 10 yrs (NSM)
• Conclusion: NSM safe in BRCA carriers.
SENTINEL NODE BIOPSY
•
Sentinel node biopsy after neoadjuvant chemotherapy
• S2-1 (ACOSOG)
• S2-2 (SENTINA trial)
SENTINEL NODE BIOPSY
•
Sentinel node biopsy after neoadjuvant chemotherapy
• S2-1 (ACOSOG)
• Primary endpoint: FN rate < 10% if preop node +, pt received NCT, and at least
2 SN removed after NAC
• Axillary FNA or core biopsy proving disease: surgery ≤ 12 weeks p NCT
• Standard H&E stains: node + defined as tumor > .2 mm on H&E
• Predicated on NSABP B-27 with 10.7% FN rate after NCT
• Meta-analysis of 21 studies with FN rate of 12%
• 756 pts enrolled; 701 had axillary surgery; 687 attempted SNB and ALND; 637
had SLND identified and ALND completed
• 50 patients SLN not detected
SENTINEL NODE BIOPSY
•
Sentinel node biopsy after neoadjuvant chemotherapy
•
S2-1 (ACOSOG)
• Type of biopsy: FNA (39%) , core biopsy (61%)
• T1 (14%); T2 (55%); T3 (25%)
• Hormone +/Her2 neg (45%); Her2 pos (30%); Trip neg (24%)
• Anthracycline +/- taxane (80%), taxane based (17%)
•
SN identification rate
• cN1 (92.9%), cN2 (89.5%)
•
SN H&E results
• 40% node negative
• 60% residual nodal disease
• SN positive 326 patients (86%)
• SN negative and ALN positive 56 patients (14%)
• For patients with cN1 disease and 2 SN:FN rate = 12.6%
SENTINEL NODE BIOPSY
•
Sentinel node biopsy after neoadjuvant chemotherapy
•
S2-1 (ACOSOG)
• Technique: FN rate
• blue dye 22.5%; radiocolloid 20%; both 10.8% (p=.046)
• 2 SN (21.1%) ; 3 SN (9%); 4 SN 6.7%); 5 SN (11%) (p=.004)
• 1 SN had FN rate of 31.5%
• Role of clip placement
• 172 of 525 pts (32.8%) had clip placed in LN at time of dx
• If clip placed and found in SN, FN rate 7.4%
• Further evaluation
• QOL, lymphedema, improve patient selection based on response to NCT
• Alliance A11202: if SN +, randomization to breast, chest wall, and regional
nodal RT +/- cALND
SENTINEL NODE BIOPSY
•
Sentinel node biopsy after neoadjuvant chemotherapy
• S2-1 (ACOSOG)
• S2-2 (SENTINA trial)
SENTINEL NODE BIOPSY
•
Sentinel node biopsy after neoadjuvant chemotherapy
• S2-2 (SENTINA trial): Sentinel Lymph Node Biopsy Before or After Neoadjuvant
Chemotherapy (German Multi-Institutional Trial)
• 4 arm, prospective, multi-center study: colloid mandatory, no IHC
SENTINEL NODE BIOPSY
•
Sentinel node biopsy after neoadjuvant chemotherapy
• S2-2 (SENTINA trial): Sentinel Lymph Node Biopsy Before or After Neoadjuvant
Chemotherapy (German Multi-Institutional Trial
SENTINEL NODE BIOPSY
•
Sentinel node biopsy after neoadjuvant chemotherapy
• S2-2 (SENTINA trial): Sentinel Lymph Node Biopsy Before or After Neoadjuvant
Chemotherapy (German Multi-Institutional Trial
SENTINEL NODE BIOPSY
•
Sentinel node biopsy after neoadjuvant chemotherapy
• S2-2 (SENTINA trial): Sentinel Lymph Node Biopsy Before or After Neoadjuvant
Chemotherapy (German Multi-Institutional Trial
APBI
•
Single fraction IORT
• S4-2 TARGIT for early stage breast cancer (S4-2)
• Verona experience (P4-16-08)
APBI
•
Single fraction IORT
• S4-2 TARGIT for early stage breast cancer (S4-2)
• TARGIT vs WB-XRT
• TARGIT “ideal” pt age ≥ 45; T preferably ≤ 3.5 cm; MRI not required
• 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 years
• 34 pts IBTR
• TARGIT IBTR rate 2% > WB-XRT – unselected
• TARGIT IBTR rate .18% > WB-XRT – selected for PgR + pts
APBI
•
Single fraction IORT
• S4-2 TARGIT for early stage breast cancer (S4-2)
APBI
•
Single fraction IORT
• S4-2 TARGIT for early stage breast cancer (S4-2)
APBI
•
Single fraction IORT
• S4-2 TARGIT for early stage breast cancer (S4-2)
APBI
•
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
SUMMARY – SABCS SURGICAL PRESENTATIONS
•
Excision still recommended for atypical breast lesions
•
Central pathology review may alter patient management in 10% of patients
•
MRI will continue to identify satellite tumor foci in newly dx IBC with uncertain clinical benefit
•
Research efforts will continue to identify biological markers to inform need for re-excision and
adjuvant local therapies for DCIS and invasive breast cancer
•
Excision to tumor-free margins remains standard of care for breast conservation
•
Rates of breast conservation vs mastectomy may be more stable than some have reported
•
Use of nipple-areolar sparing mastectomy is increasing for those who choose mastectomy
•
Sentinel node biopsy after neoadjuvant chemotherapy requires resection of nodes with proven
disease: dual tracer and/or localization of clipped nodes. Repeat SN bx alone to be avoided in
setting of proven nodal disease
•
Single fraction IORT may be equivalent to WB-XRT in select patient subsets, with higher
recurrence rates in unselected patients: longer f/u required to determine if these results are
sustainable