surgical advances in the treatment of breast...

Surgical Advances in the Treatment of

Breast Cancer

Laura Kruper, MD, MSCE

Chief, Breast Surgery

DISCLOSURE

• Nothing to disclose

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 overall mortality rates:

IORT 3.9 %

EBRT 5.3 %

P-value 0.099

5-year regional recurrence rates:

IORT 4.9 %

EBRT 4.4 %

P-value NS

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

Kaplan Meyer analysis breast cancer/non-breast cancer deaths


Pre-pathology


TARGIT 2.1 %

EBRT 1.1 %

P-value 0.31

Post-pathology


TARGIT 5.4 %

EBRT 1.7 %

P-value 0.059


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

MC418R1 4/12

3-4 cm, 4-5cm, 5-6cm

Fill Balloon and Close Cavity With Sutures

MC418R1 4/12

Photo Courtesy of Dr Lauren Schnaper, GBMC, Baltimore, MD

Measure Skin Bridge (=/>1cm)

Minimal distance from balloon applicator surface to skin must be 1cm.

Ultrasound to Confirm Skin Bridge

Photo Courtesy of Dr Lauren Schnaper, GBMC, Baltimore, MD

Personnel remaining in room must be shielded

• Lead Apron

• Behind Rolling shield

Deliver Radiation Treatment

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

Kurian et al, JAMA 2014

Surgery in Age Groups over Time

Kurian et al, JAMA 2014

Surgical Trends in Young Women

Tissue Expander

• Post-operatively adjustable temporary saline implant

Implant/Expander Coverage and Support

Bilateral Skin Sparing Mastectomies

Courtesy of Dr. Andersen

Tissue Expanders


Nipple Reconstruction


2 years postop


3 years postop s/p structural fat grafting


SINGLE STAGE RECONSTRUCTION

Preop 6 weeks after surgery

Courtesy of Dr. Li

PreOp PostOp


Courtesy of Dr. Tan

Preop 2 years post-op

Lymph Nodes

SLNB ALND P-value

Local

Recurrence

1.6% 3.1% p = 0.11

Locoregional

Recurrence Free

Survival

96.7% 95.7% p = 0.28

Disease Free

Survival

83.9% 82.2%

p = 0.14

Overall Survival 92.5% 91.8% p = 0.25

SLNB ALND P-value

Local

Recurrence

5.3% 6.2% p = 0.36

Loco-regional

Recurrence Free

Survival

83.0% 81.2% p = 0.41

Disease Free

Survival

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

Fisher B, JCO 1997

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

Can we do SLNBx after NAC to avoid ALND?

SLN Biopsy in the setting of NAC

King T, SABCS 2016

Clinically node negative: SLNBx before or after?

SLNBx and NAC:cN0

King T, SABCS 2016

SLN identification rate similar before/after NAC

FNR similar before/after NAC

Sentinel Lymph Node Biopsy NAC

King T, SABCS 2016

Clinically node positive patient that converts to cN0?

Pre- vs Post-Treatment Nodal Status:

Impact on LRR

King T, SABCS 2016

Clinically node positive patients that remain node positive

have high rates of LRR: important to distinguish

ACOSOG Z1071 – cN1 patients

Boughey JC, JAMA 2013

SLNBx after NAC: cN1 convert cN0

King T, SABCS 2016

False negative rate by number of SLN

ACOSOG Z1071 – cN1 patients

Boughey JC, JAMA 2013

King T, SABCS 2016

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

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

King T, SABCS 2016

Patients who convert to cN0 after initially being cN1 do as

well as patients who were initially cN0

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

King T, SABCS 2016

When SLN metastasis definition is broadened to include

Isolated tumor cells (ITC) on IHC or H&E, FNR <10

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

• 7th edition AJCC TNM Staging Manual

– ypN0i+ or ypN1miresidual 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

Caudle AS, JCO 2016

Clipped node +/- SLN to reflect status of nodal basin in all

patients undergoing NAC

MD Andersen: Targeted Axillary Dissection

Post NAC Trials of Axillary Management

King T, SABCS 2016

Thank you for your attention!

Questions at panel discussion

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