Surgical Considera0ons with Neoadjuvant Treatment in Breast Cancer

Transcription

1 Surgical Considera0ons with Neoadjuvant Treatment in Breast Cancer David R McCready MD MSc FRCSC FACS GaAuso Chair in Breast Surgical Oncology Professor of Surgery, University of Toronto Princess Margaret Cancer Centre Mt Sinai Hospital

2 Disclosures Shares in Johnson and Johnson Par0cipant in NRG/NSABP and Alliance clinical trials

3 Topics Covered Basic truths Outcomes related to response and subtype Evalua0on of response Breast conserva0on Axillary assessment

4 Basic Truths For locally advanced breast cancers, preopera0ve systemic therapy is standard and best Breast conserving surgery, when all evidence of disease is removed, plus breast radia0on provides equal survival rates compared to mastectomy with or without neoadjuvant chemotherapy (NAC) For early breast cancers, preopera0ve systemic therapy provides equivalent mortality reduc0on as the same postopera0ve systemic treatment

5 Outcomes Related to Response and Subtype Main endpoint / measure of response is pcr (no residual invasive) or not But this may change (RCB, CPS-EG) In absense of molecular profiling, IHCconstructed subtype is best approxima0on of tumor subtype. HR (ER or PR) +, Her2 neu - HR +, Her2 + HR -, Her2 + HR -, Her2 - (triple nega0ve)

6 Outcomes Related to Response and Subtype NSABP B-18, B-27: Complete Responders (pcr) Have BeAer Survival B-18 B-18 B-27 B-27 Rastogi, J Clin Oncol 2008; 26 (5):778

7 Outcomes Related to Response and Subtype Pathologic Complete Responses According to Constructed Subtype in I-SPY 1 Trial % 39 % 35 % 30 HR+ Her2 - pcr% 25 HR+ Her2+ 20 HR- Her % HR- Her2-5 0 Esserman J Clin Oncol 2012 ;30:3242

8 Outcomes Related to Response and Subtype Prognosis: pcr Predicts RFS More Effec0vely by Cancer Subset 20% Esserman J Clin Oncol 2012 ;30:3242

9 Outcomes Related to Response and Subtype Prognosis: pcr Predicts RFS More Effec0vely by Cancer Subset TN 40% 40% Esserman J Clin Oncol 2012 ;30:3242

10 Evalua0on of Response Single best modality is MRI MRI-measured volume predicts response in first couple of cycles Mammogram adds to accuracy in all tumor subtypes r(mr)cr not accurate enough to rule out residual disease and avoid surgery r(mr)cr related to subtype Marinovich, JNCI. 2013;105:321 De Los Santos, Cancer 2013;119:1776 Hylton Radiology 2012:263(663)

11 Evalua0on of Response Meta-analysis of MRI in Detec0ng Residual Breast Cancer Afer NAC! 44 studies, 2050 pts.! MRI most accurate vs Mammography, US, Physical Exam! Pooled es0mates to detect pcr :! Sensi0vity = 92%! correct detec0on of residual tumor! Specificity = 60%! correct detec0on of pcr Marinovich, JNCI. 2013;105:321

12 746 pa0ents with MRI pre and post neoadjuvant chemotherapy rcr = radiologic CR; pcr no IDC / DCIS Categorized by IHC subtype pcr r(mr)cr HR+/Her % 13% HR-/Her % 38% HR+/Her % 25% HR-/Her2- (TN) % 37% De Los Santos, Cancer 2013;119:1776

13 pcr rates vary by molecular subtype Highest pcr in Her2+ and TN 746 pa0ents with MRI pre and post neoadjuvant chemotherapy rcr = radiologic CR; pcr no IDC / DCIS Categorized by IHC subtype pcr r(mr)cr HR+/Her % 13% HR-/Her % 38% HR+/Her % 25% HR-/Her2- (TN) % 37% De Los Santos, Cancer 2013;119:1776

14 pcr rates vary by molecular subtype Highest pcr in Her2+ and TN MRI rcr rates vary by molecular subtype Lowest rcr rate in HR+/ Her2-746 pa0ents with MRI pre and post neoadjuvant chemotherapy rcr = radiologic CR; pcr no IDC / DCIS Categorized by IHC subtype pcr r(mr)cr HR+/Her % 13% HR-/Her % 38% HR+/Her % 25% HR-/Her2- (TN) % 37% De Los Santos, Cancer 2013;119:1776

15 Breast ConservaQon arer NAC NSABP B-18 Clinical Tumor Size (cm) at Presenta8on Lumpectomy Proposed Pre- NAC (%) Lumpectomy Performed NAC (%) All Pa0ents < >

16 Breast ConservaQon arer PreoperaQve Chemotherapy (NAC) 226 pts, T > 3 cm, age < ccr s (only 6 path neg) Quadrantectomy in 203 (90%) Microcalcifica0ons in 94 (42%) Calcifica0ons did not disappear but aggregated and lef scaaered islands 12 / 203 (6%) LRR at mean 36 months Veronisi, Ann Surg, 1995

17 Breast ConservaQon arer NAC Downsizing to be eligible for BCS EORTC 10902: Pa8ents receiving NAC Planned Mastectomy Performed Mastectomy Performed BCS Total 189 (77%) 57 (23%) % Converted from mast to BCS Planned BCS 14 (18%) 63 (82%) 77 Total Van der Hage J Clin Oncol 2001; 19:4224

18 Breast ConservaQon arer NAC Local Regional Recurrence Local breast recurrence rates not increased in pa0ents made eligible for BCS by NAC LRR similar in those with mastectomy and BCS afer NAC Surgery 10-Yr LRR Local Regional Mastectomy 12.3% 8.9% 3.4% BCS 10.3% 8.1% 2.2% Mamounas. J Clin Oncol 2012;30:3960 Mieog. Br J Surg 2007;94:1189

19 Local Recurrence (5 Yrs) afer NAC and BCS is Associated with Tumor Subtype pcr% Column1 LRR % LRR %; HR+ Her2 - HR+ Her2+ HR- Her2+ HR- Her2- LRR% HR+ Her2- HR+ Her2+ HR- Her HR- Her2- Swisher Annals Surg Onc (749)

20 Local Recurrence (5 Yrs) afer NAC + BCS is Associated with pcr Status and Tumor Subtype 20 LRR% No pcr No pcr No pcr No pcr pcr pcr pcr pcr HR+ Her2 - HR+ Her2+ HR- Her2+ HR- Her2- Swisher Annals Surg Onc (749)

21 Clinically Meaningful Tumor Reduc0on Varies by MRI Phenotype and Molecular Subtype I-SPY 1 TRIAL 90% of Her2 + and TN pa0ents had clinically meaningful tumor reduc0ons (post NAC < 4cm) Actual BCS was not significantly altered Mukhtar, Ann Surg Onc 2013;20:3823

22 Breast ConservaQon arer NAC Principles If tumor is unicentric and, afer response, all evidence of disease can poten0ally be excised with acceptable cosmesis, consider breast conserva0on + RT Mark tumour loca0on(s) with clip(s) Follow breast imaging and clinical response Excise all evidence of post-nac disease with margin of normal 0ssue (not necessarily pre-nac tumor volume) If margins posi0ve, or mul0ple margins close with diffuse paaern +/- LVI consider mastectomy

23 Axillary Assessment Is SLNB accurate afer NAC for cn0 pa0ents? If N1 at presenta0on What is axillary % pcr afer NAC? Is SLNB accurate in these pa0ents? Do those with pcr (now N0) need axillary RT? Do those with residual disease need axillary dissec0on?

24 Axillary Assessment Meta-Analysis of SLNB afer Preopera0ve Chemotherapy in cn0 Pa0ents Krag et al. Lancet Oncology 2007;8:881 Tan et al. JSO 2011;104(1):97

25 Axillary Assessment for those N1 at presentaqon %pcr (MSKCC NAC Surgical Database) % pcr Axilla % pcr Breast +Axilla % pcr

26 If senqnel node biopsy (SNB) is accurate (FNR < 10%) and N0 in this se`ng, compleqon node dissecqon (CND) morbidity could be avoided.

27 Axillary Assessment SN FNAC Results 153 accrued 145 study eligible 127 technical success 87.6% 7 non-eligible 1 consent withdrawal 18 technical failure 44 axillary pcr (30%) 66.7% (12/18) node positive if technical failure 83 node positive and SNB + CND 7 false negative False negative rate = 8.4% (7/83) 95% CI = [3.3, 15.9]

28 Axillary Assessment SN FNAC FNR, NPV and Accuracy Improved if ITC s in SLN Are Considered Posi0ve SNs with metastases < 0.2mm: posi8ve vs. nega8ve FNR NPV Accuracy ypn0(i+) SN = node posi8ve 8.4% (7/83) 86.3% (44/51) 94.5% (120/127) ypn0(i+) SN = node nega8ve 13.3% (11/83) 80.0% (44/55) 91.3% (116/127) FNR = False nega0ve rate NPV = Nega0ve predic0ve value

29 Axillary Assessment SN FNAC Factors related to FNR To minimize false neg rate Try to get > 1 node Use dual tracers Use IHC

30 Axillary Assessment for those N1 at presentaqon Trials of SLNB Receiving NAC SN FNAC ACOSOG Z1071 SENTINA N (cn+) Mapping Agents Techne0um required + Blue dye recommended Dual recommended (79%) Techne0um required Axillary pcr 35 % 41% 52% ypn0 FNR ( Total) 8.4%* 12.6% 14.2% 1 SLN 18.2% 31.5% 24.3% 2 SLN 4.9% 21.1% 18.5% >3 SLN 9.1% 7.3%

31 Axillary Assessment for those N1 at presentaqon Targeted Sen0nel Node Biopsy: Clip and Remove the FNA Posi0ve Node Sen8nel Node Biopsy Alone Clipped Node Alone Targeted SLNB (clipped and sen8nel node) N False Nega0ve rate 10.1 %* 4.2% 2.0% 95% CI [4.2, 19.8] [1.4, 9.5] [0.05, 10.7] * In this study, the FNR was the same if dual or single agent mapping was used and it didn t change if > 2 or < 2 SLN s were retrieved Caudle et al. J Clin Oncol 2016

32 Axillary Assessment LRR is More Related to Response afer NAC than Nodal Status at Presenta0on " """ = cn(+) = cn(-) ypn+ ypn- / No Breast pcr ypn- / Breast pcr Mamounas et al

33 Clinical Trials for cn1 Pa0ents Receiving NAC Biopsy proven node posi0ve NAC SLNB - SLNB + Node RT Observa0on ALND + RT Node RT NRG / NSABP B 51 Alliance 11202

34 Axillary Management Afer NAC T1-3 cn0 at presenta0on SLNB afer NAC T1-3 cn1 at presenta0on Clip / mark node if feasible SLNB (plus clipped node afer NAC) cn2 at presenta0on ALND probably safest ALND for any posi0ve SLN (inc ITC s) on frozen or final sec0on TIPS # Op0mize SLNB Dual Tracer Try to find at least 2 nodes (Hot, Blue, or Palpable suspicious) IHC # If not clipping node and no IHC then consider ALND if < 2-3 SLN s

35 Summary Subtype maaers MRI helpful, but not mandatory If all evidence of remaining disease can be removed then breast conserva0on possible Neoadjuvant chemotherapy can reduce need for ALND

36 Thank You

37

38 Which of the following is false? 1. The false nega0ve rate of sen0nel node biopsy afer NAC is < 10% 2. The false nega0ve rate of sen0nel node biopsy afer NAC for pa0ents presen0ng with N1 disease can be < 10% 3. Axillary pcr afer NAC for pa0ents presen0ng with N1 disease is < 10% 4. The false nega0ve rate of sen0nel node biopsy can vary with technique and pathology methodology

39 Which of the following is false? 1. The radiological CR rate (% rcr) afer NAC varies by tumor subtype 2. The pathological CR rate (% pcr) afer NAC varies by tumor subtype 3. HR+ (ER+PR+) Her2 tumors don t achieve enough of a clinical response from NAC to facilitate breast conserva0on 4. TN pa0ents without a pcr have significantly poorer prognoses

40