Surgical Advances in the Treatment of Breast Cancer Laura Kruper, MD, MSCE Chief, Breast Surgery
Nothing to disclose DISCLOSURE
LESS IS MORE Radiation Lymph nodes Reconstruction
Less is More! Radiation Reconstruction Lymph nodes
IORT: Intra-Operative Radiation Therapy TARGIT A Trial: targeted single dose intra-operative radiotherapy versus external beam radiation therapy (EBRT) Delivers high dose radiation at time of breast cancer surgery in shorter amount of time than traditional radiation Inferiority trial: pre-specified 2.5% margin at 5 years Enrollment 2000-2012 in 33 centers, 11 countries 1721 patients randomized to TARGIT, 1730 to EBRT Supplemental EBRT to 15.2% TARGIT patients (N=239) Timing of randomization also evaluated: Pre-pathology: at time of initial surgery Post-pathology: after lumpectomy, separate procedure Vaidya JS, Lancet 2014
5-year local recurrence rates: TARGIT 3.3 % EBRT 1.3 % P-value 0.042 5-year regional recurrence rates: IORT 4.9 % EBRT 4.4 % P-value NS 5-year overall mortality rates: IORT 3.9 % EBRT 5.3 % P-value 0.099 Vaidya JS, Lancet 2014
Kaplan Meyer analysis breast cancer/non-breast cancer deaths 5-year breast cancer death rates: TARGIT 2.6 % EBRT 1.9 % P-value 0.56 5-year non-breast cancer death rates: TARGIT 1.4 % EBRT 3.5 % P-value 0.009 Vaidya JS, Lancet 2014
Pre-pathology 5-year local recurrence rates: TARGIT 2.1 % EBRT 1.1 % P-value 0.31 Post-pathology 5-year local recurrence rates: TARGIT 5.4 % EBRT 1.7 % P-value 0.059 Vaidya JS, Lancet 2014
Example of Criteria Inclusion Criteria 45 years or older Single focus of cancer Infiltrating ductal carcinoma DCIS <2.5cm in diameter BRCA gene negative SLNs are negative Exclusion Criteria Multifocal disease Node positive Infiltrating lobular carcinoma EIC or lymphovascular invasion on biopsy Skin spacing < 1 cm by intraoperative ultrasound More aggressive biology (i.e., triple negative)
ebx High Dose, Low Energy Delivers Less Radiation to Critical Structures (heart, lung) Dickler, et al. A dosimetric comparison of MammoSite high dose rate brachytherapy and Xoft Axxent electronic brachytherapy, Brachytherapy (6) 2007, 164-168.. Slide courtesy of Dr. David Wazer MC418R1 4/12
Xoft Balloon Applicators 3-4 cm, 4-5cm, 5-6cm MC418R1 4/12
Fill Balloon and Close Cavity With Sutures Photo Courtesy of Dr Lauren Schnaper, GBMC, Baltimore, MD
Ultrasound to Confirm Skin Bridge Minimal distance from balloon applicator surface to skin must be 1cm. Measure Skin Bridge (=/>1cm) Photo Courtesy of Dr Lauren Schnaper, GBMC, Baltimore, MD
Deliver Radiation Treatment Personnel remaining in room must be shielded Lead Apron Behind Rolling shield
Radiation Therapy and Lumpectomy Completed
RECONSTRUCTION Tissue Expanders Direct implant-based reconstruction
More women are choosing implant reconstruction Albornoz CR et al, PRS 2009
Why are more women choosing bilateral mastectomies? Albornoz CR et al, PRS 2013
Surgery in Age Groups over Time Kurian et al, JAMA 2014
Surgical Trends in Young Women Kurian et al, JAMA 2014
Tissue Expander Post-operatively adjustable temporary saline implant
Implant/Expander Coverage and Support
Bilateral Skin Sparing Mastectomies Courtesy of Dr. Andersen
Tissue Expanders Courtesy of Dr. Andersen
Nipple Reconstruction Courtesy of Dr. Andersen
2 years postop Courtesy of Dr. Andersen
3 years postop s/p structural fat grafting Courtesy of Dr. Andersen
Courtesy of Dr. Andersen
SINGLE STAGE RECONSTRUCTION
Preop 6 weeks after surgery Courtesy of Dr. Li
PreOp PostOp Courtesy of Dr. Andersen
Preop 2 years post-op Courtesy of Dr. Tan
Lymph Nodes
SLNB ALND P-value Local Recurrence Locoregional Recurrence Free Survival Disease Free Survival 1.6% 3.1% p = 0.11 96.7% 95.7% p = 0.28 83.9% 82.2% p = 0.14 Overall Survival 92.5% 91.8% p = 0.25
SLNB ALND P-value Local Recurrence Loco-regional Recurrence Free Survival Disease Free Survival 5.3% 6.2% p = 0.36 83.0% 81.2% p = 0.41 80.2% 78.2% p = 0.32 Overall Survival 86.3% 83.6% p = 0.72
Overall Survival Disease-Free Survival
Axillary Management Neoadjuvant Chemotherapy Neoadjuvant chemotherapy (NAC) downstages axilla ~40% of patients Potential to consider SLNBx after NAC avoid ALND Should management depend on pre-treatment clinical nodal (cn) stage? Clinically node negative vs node positive King T, SABCS 2016
Axillary Downstaging NSABP B-18 Can we do SLNBx after NAC to avoid ALND? Arguments for/against SLNBx prior to NAC Need status of LN without confounding of NAC Selection of optimal loco-regional XRT Requires 2 surgical procedures Commits pre-treatment node+ to ALND Fisher B, JCO 1997
SLN Biopsy in the setting of NAC Clinically node negative: SLNBx before or after? King T, SABCS 2016
SLNBx and NAC:cN0 SLN identification rate similar before/after NAC FNR similar before/after NAC King T, SABCS 2016
Sentinel Lymph Node Biopsy NAC Clinically node positive patient that converts to cn0? King T, SABCS 2016
Pre- vs Post-Treatment Nodal Status: Impact on LRR Clinically node positive patients that remain node positive have high rates of LRR: important to distinguish King T, SABCS 2016
ACOSOG Z1071 cn1 patients Boughey JC, JAMA 2013
SLNBx after NAC: cn1 convert cn0 False negative rate by number of SLN King T, SABCS 2016
ACOSOG Z1071 cn1 patients False negative rate by number of SLN SLNBx after NAC: cn+ convert to cn0 Consistent unacceptable FNR unless >3 SLN removed Residual disease potentially resistant to tx no data on LRR in this setting Importance of path node status in predicting LRR Implications for RT Boughey JC, JAMA 2013 King T, SABCS 2016
SLNBx after NAC Clinically Node Negative cn0: SLNBx after NAC Intra-operative frozen section of SLN calnd for failed mapping calnd for any positive LN including micromets Radiation tx decisions made with combo of pre-tx factors & final path status (breast & nodes) King T, SABCS 2016
Pre- vs Post-Treatment Nodal Status: Impact on LRR Patients who convert to cn0 after initially being cn1 do as well as patients who were initially cn0 King T, SABCS 2016
SLNBx after NAC: cn1 convert cn0 Methods to minimize FNR: Dual agent mapping Normal exam after NAC Remove >3 SLNs Include IHC detected disease as node + Leave clip at time of biopsy & localize for SLN King T, SABCS 2016
Methods Impacting FNR of SLN: ACOSOG Z1071 When SLN metastasis definition is broadened to include Isolated tumor cells (ITC) on IHC or H&E, FNR <10 King T, SABCS 2016
Evaluation of SLN after NAC Significance of residual ITCs or disease <0.2mm (ypn0i+) after NAC unclear 2012 WHO Classification: small nodal mets & ITCs evidence of incomplete response 7 th edition AJCC TNM Staging Manual ypn0i+ or ypn1mi residual nodal disease ALND remains standard of care King T, SABCS 2016
Methods Impacting FNR of SLN: ACOSOG Z1071 Boughey JC, SABCS 2014 King T, SABCS 2016
Methods Impacting FNR: Harvesting Clipped and SLN after NAC MD Andersen: Targeted Axillary Dissection Clipped node +/- SLN to reflect status of nodal basin in all patients undergoing NAC Caudle AS, JCO 2016
Post NAC Trials of Axillary Management King T, SABCS 2016
Thank you for your attention! Questions at panel discussion