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Frederick M. Dirbas, M.D. Associate Prof Surgery, Physician Leader Breast Clinical Cancer Program Stanford Cancer Institute SABCS 2012 SURGERY HIGHLIGHTS.

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Presentation on theme: "Frederick M. Dirbas, M.D. Associate Prof Surgery, Physician Leader Breast Clinical Cancer Program Stanford Cancer Institute SABCS 2012 SURGERY HIGHLIGHTS."— Presentation transcript:

1 Frederick M. Dirbas, M.D. Associate Prof Surgery, Physician Leader Breast Clinical Cancer Program Stanford Cancer Institute SABCS 2012 SURGERY HIGHLIGHTS

2 FIBRO-EPITHELIAL TUMORS Phyllodes tumors of the breast: what predicts recurrence? (P ) Retrospective analysis ( ), 87 patients, median age 47, mean size 46.6 mm BenignBorderlineMalignant No. pts60 (69%)10 (11.5%)17 (19.5%) Median age45 55 BCS/Mast66/2 (97%)11/6 (65%) RT02 IBTR6 (8.6%) 5 (29.4%) Metastases02 (followed IBTR) (18.2%) Time to mets--2.5 yrs Relapse free91.7%90%70.6%

3 FIBRO-EPITHELIAL TUMORS Phyllodes tumors of the breast: what predicts recurrence? (P )

4 ATYPICAL EPITHELIAL LESIONS AND EXCISION Is surgical excision warranted for atypical lesions found on core biopsy? Flat epithelial atypia – Loyola (P ) , 14 patients. 3 pts (21.4%) upgraded to DCIS or IBC on excision Flat epithelial atypia – 3 Dutch hospitals (P ) , 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 (P ) , 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

5 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? (P ) – Gustave Roussy. Retrospective analysis , 205 patient training set Sens 77.8%, Sp 66.1%, PPV 40%, NPV 91.1%

6 CENTRAL REVIEW OF PATHOLOGY AFTER LUMPECTOMY AND SNB FOR NONPALPABLE IBC Use of expert breast pathologists to confirm diagnosis (P ) – UMC Utrecht 310 pts with IBC and SN bx. 24% discordance rate, 9% change in mgmt

7 BREAST MRI , 678 patients w staging MRI, ethnically mixed population (P ) - USC 141 pts (21%) had non-index lesions found 57 pts (8.4%) had 62 occult cancers detected (49 invasive, 9 in-situ)

8 BREAST MRI pts with ductolobular IBC, prospectively offered breast MRI (P ) 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%)

9 DUCTAL CARCINOMA IN SITU Utility margin index to predict residual DCIS (P ) - Yale 2009, 177 pts: closest margin distance (mm)/extent of DCIS (mm) 87 pts underwent re-excision: PR status most predictive of resid disease

10 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 ) – Univ of Manchester 1990 – 2010, 314 pts

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12 DUCTAL CARCINOMA IN SITU Use of Ki-67 in predicting LRR of DIN after RT (PD-04-07) – EIO : 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

13 DUCTAL CARCINOMA IN SITU Prediction of recurrent pure DCIS vs IBC +/- DCIS (PD-04-05) – MSKCC , 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

14 DUCTAL CARCINOMA IN SITU Prediction of recurrent pure DCIS vs IBC +/- DCIS (PD-04-05) – MSKCC

15 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 (P ) Technique Intraoperative ultrasound (PD-04-01) Use of radioguided localization (ROLL) (P ) Radiofrequency ablation – long term results (P ) Repeat breast conservation (P )

16 BREAST CONSERVATION SURGERY What influences rates of BCS? (SEER) (PD-04-04) , 437 breast centers: 77, 248 pts Stage 0-II, 64.2% BCS No change during study period towards increase/decrease BCS.

17 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

18 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

19 BREAST CONSERVATION SURGERY Breast conservation after neoadjuvant therapy in clinical stage III pts (P ) - Seoul , 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.

20 BREAST CONSERVATION SURGERY Intraoperative ultrasound improves surgical accuracy (PD-04-01) - Netherlands , 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

21 BREAST CONSERVATION SURGERY Cost effectiveness of ROLL vs wire guided localization (P ) – 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

22 BREAST CONSERVATION SURGERY Radiofrequency ablation – long term results (P ) – Kanazawa Hosital, Japan RFA is a promising technique for non-surgical local therapy. 95 deg C , 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

23 BREAST CONSERVATION SURGERY Repeat breast conservation (P ) GEC-ESTRO Is BCT safe for IBTR? , 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%

24 MASTECTOMY Nipple-Areolar sparing Nipple-areolar complex ischemia ASBS registry (P ) 33/265 mastectomies had some degree of ischemia. 11% epidermolysis; 1% debridement;.3% surgical excision. No correlation w/ technique NAS increasing per SEER (P ) , NSM. Most T < 2 cm and node -. Increase in frequency Intraoperative biopsy: to freeze or not to freeze (P ) 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 (P ) , 293 M in 154 pts. 70 pts BRCA % occult DCIS or IBC 2/70 pts had late recurrence: 3yrs (non-NSM); 10 yrs (NSM) Conclusion: NSM safe in BRCA carriers.

25 SENTINEL NODE BIOPSY Sentinel node biopsy after neoadjuvant chemotherapy S2-1 (ACOSOG) S2-2 (SENTINA trial)

26 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

27 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%

28 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

29 SENTINEL NODE BIOPSY Sentinel node biopsy after neoadjuvant chemotherapy S2-1 (ACOSOG) S2-2 (SENTINA trial)

30 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

31 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

32 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

33 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

34 APBI Single fraction IORT S4-2 TARGIT for early stage breast cancer (S4-2) Verona experience (P )

35 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%) : 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

36 APBI Single fraction IORT S4-2 TARGIT for early stage breast cancer (S4-2)

37 APBI Single fraction IORT S4-2 TARGIT for early stage breast cancer (S4-2)

38 APBI Single fraction IORT S4-2 TARGIT for early stage breast cancer (S4-2)

39 APBI Single fraction IORT Verona experience, phase II single fraction IORT with IOERT (P ) , 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

40 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


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