SABCS 2012 Surgery Highlights

Frederick M. Dirbas, M.D.

Associate Prof Surgery, Physician Leader Breast Clinical Cancer Program

Stanford Cancer Institute

SABCS 2012SURGERY HIGHLIGHTS

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 MalignantNo. 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 1 st

• 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 2nd 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)


• 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


• 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%


• 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


• S2-1 (ACOSOG)

• S2-2 (SENTINA trial)


• 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


• 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)



• 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


• 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

SABCS 2012 Surgery Highlights

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