*cCR: complete clinical response

Cortazar et al., Lancet. 2014. PMID: 24529560

Cortazar et al., Lancet. 2014. PMID: 24529560

Cortazar et al., Lancet. 2014. PMID: 24529560Spring L. et al., 2016 AACR Annual Meeting. Abstract 1439.

Presented By Sunil Verma at 2016 ASCO Annual Meeting

King, T. et al., Nat Rev Clin Oncol. 2015. PMID: 25850554Schneeweiss A et al. Ann Oncol. 2013. PMID: 23704196

van la Parra and Kuerer HM, Breast Cancer Res. 2016. PMID: 26951131Ring A. et al., J Clin Oncol. 2003. PMID: 14673041

van la Parra and Kuerer HM, Breast Cancer Res. 2016. PMID: 26951131Ring A. et al., J Clin Oncol. 2003. PMID: 14673041

75%

92%

79%

83%

Ultrasound assessment

van la Parra and Kuerer HM, Breast Cancer Res. 2016. PMID: 26951131Ring A. et al., J Clin Oncol. 2003. PMID: 14673041

underscores therapeutic strategies reflecting a previous era and

the essential need to utilize state-of-the-art breast imaging with biopsy.

“Pathologic”

confirmation

What is the

role of surgery in

cCR patients?

Fine needle aspiration

Core needle biopsy

Vacuum-assisted biopsy

Supporting predictors: Tumor biology (subtypes)

Imaging studies

Any alternatives?

Who are the selected pts?

Is the alternative sufficient

for pathologic evaluation?

Can we avoid

surgery in

selected patients?

NeoadjuvantChemotherapy

Clinical and Radiologic CR

Residual Lesion

Minimally invasive biopsy

non-pCR(positive)

Prediction

Criteria for CR?

Biopsy

Modality?

Pathological

interpretation?

pCR(negative)

No Further Surgery

Wide Local Excision

Radio

thera

py

randomization

Marinovich ML et al., J J Natl Cancer Inst. 2013. PMID: 23297042King, T. et al., Nat Rev Clin Oncol. 2015. PMID: 25850554

Loo CE et al., J Clin Oncol. 2011. PMID: 21220595

TNBC HER2(+) ER(+)

Heil et al., Br J Cancer 2015. PMID: 26554654

164 patients, CNB or VABB

Existence of a clip marker tended to improve the NPV (odds ratio 1.98; 95% CI: (0.81; 4.85)).

None of the mammographically guided VABs (n=16) was false-negative (FNR 0%, NPV 100%).

Assessment of Representativeness

VAB-performing physician – subjective evaluation

highly probable

probable

doubtful

Pathological examination of VAB specimen after NAC

residual tumor cells

tumor bed present without residual tumor cells

neither tumor cells nor tumor bed present

Heil et al. Eur J Cancer. 2016 Nov 4;69:142-150.. PMID: 27821317

Heil et al. Eur J Cancer. 2016 Nov 4;69:142-150.. PMID: 27821317

Heil et al. Eur J Cancer. 2016 Nov 4;69:142-150.. PMID: 27821317

In biopsyNo pCR

In biopsypCR

Total

Surgical specimenNo pCR

20 1 21

Surgical specimenpCR

0 17 17

Total 20 18 38

False negative rate of 4.8% if biopsy samples were

representative

Heil et al. Eur J Cancer. 2016 Nov 4;69:142-150.. PMID: 27821317Fitzal, 15th St. Gallen International Breast Cancer Conference

cCR on MRI or USG

Correlation of pCR (ypTis(-))Negative predictive value (NPV)

False-negative rate (FNA)

NeoadjuvantChemotherapy

Clinical and Radiologic CR

Wide Local Excision

Core needle biopsy (14G x ≥5)

VABB(VACORA/

Mammotome ELITE)

Pathological evaluation

Pathological evaluation

Clip insertion for responsive tumor 20 cases

20 cases

Kim Suyeon & Nariya Cho. SNUH Radiology. Unpublished

Case Subtype NAC regimen Bx modality Preop MRI Preop USG Bx SurgicalSpecimen

1 TNBCKi67 80%

AC#4-D#4 CNB 14G x5 No residual enhancing lesion 1.7x0.5x1.9cm post-chemo change No tumor ypT0N0

2 TNBCKi67 70%

AC#4-D#4 VABB 10G x8 No residual enhancing lesion 1.5cm ill defined post chemo changes with clip insertion state

No tumor ypT0N0

3 TNBCKi67 70%

AC#4-D#4 CNB 14G x6 No enhancing lesion 2.1x1.1cm hypoechoic lesion with clip

No tumor ypT0N0

4 TNBCKi67 50%

AC#4-D#4 VABB 10G x9 No residual enhancement 2x1.3cm hypoechoic lesion with a clip

No tumor ypT0N0

5 LumB(ER 3%)Ki67 30%

AC#4-D#4 VABB 10G x6 0.2cm faint residual enhancement around the clip- near-CRSER ratio 1.0

No residual lesion No tumor ypT0N0

6 HER2(+)(ER 1%)Ki67 20%

DCbHP(TCHP)#6 CNB 14G x5 No residual enhancing lesion 1.5cm ill defined post chemo changes with clip insertion state

No tumor ypT0N1(2/17)

7 LumB20/-/2+FISH+Ki67 20%

DCbHP(TCHP)#6 CNB 14G x5 No residual enhancing lesionSER 1.06

1.4cm hypoechoic lesion with a clip

No tumor ypT0N0

8 LumB50/2/1+Ki67 70%

AC#4-D#4 VABB 10G x8 High possibility of CR, Lt, C6. 1.4x0.5x0.9cm irregular mass IDCa ypTmicN0cavity 1.8 x 0.8 x 3cm

9 HER2(+)Ki67 20%

DCbHP(TCHP)#6 CNB 14G x5 No residual enhancementSER 1.0

No residual lesion No tumor ypT0N0

10 TNBCKi67 70%

AC#4-D#4 VABB No residual enhancing lesionSER 1.4

1.7x0.7 irregular lesion with post chemo changes

No tumor ypT0N0

Case Subtype NAC regimen Bx modality Preop MRI Preop USG Bx SurgicalSpecimen

11 TNBCKi67 30%

AC#4-D#4 CNB 14G x5 No residual enhancing lesionSER 1.1

1.0x0.4x1.1cm hypoechoic area No tumor ypT0N1(2/17)

12 TNBCKi67 30%

AC#4-D#4 VABB 10G No residual enhancing lesionSER 1.0

0.9cm hypoechoic lesion Residual IDCa

ypT1N0

13 HER2(+)Ki67 40%

AC#4-DH#4 CNB 14G x5 No residual enhancing lesionSER 1.3

Disappeared previous 2.4x1.3cm mass No tumor ypT0N0

14 HER2(+)ER 2%Ki67 7%

DCbHP(TCHP)#6 VABB 10G No residual enhancing lesion 1.4x0.4cm post chemo changes No tumor ypT0N0

15 LumB70/80/3+Ki67 40%

DCbHP(TCHP)#6 CNB 14G x5 No residual enhancing lesionSER 1.1

1.7x0.3cm hypoechoic area No tumor ypT0N0

16 LumA80/2/0Ki67 5%

AC#4-D#4 VABB 10G No residual enhancing lesion Clip without associated residual mass No tumor Preliminary:no residual tumor

7 TNBC

6 HER2+ (4 HR(-); 2 HR(+))

2 Lum B (HER2-) – high Ki-67

1 Lum A

100% NPV

0% FNR

AC#4 – D#4

AC#4 – DH#4

TCHP#6

Can we avoid

surgery in

selected patients?

“Pathologic”

confirmationVacuum-assisted biopsy

Core needle biopsy?

Supporting predictors: TNBC & HER2+, LumB?

MRI

RESPONDER trial

NCT02945579

(MD Anderson)

Korean Breast Cancer

Study Group

(KBCSG)

What is the

role of surgery in

cCR patients?

Any alternatives?

NeoadjuvantChemotherapy

Clinical and Radiologic CR

Residual Lesion

Minimally invasive biopsy

Negative(pCR)

Positive(non-pCR)

No Further Surgery

Wide Local Excision

Radio

thera

py

randomization

Inclusion Criteria

- initial size (cT1-2)

- nodal status (cN0-1)

- TNBC & HER2, LumB?

Biopsy Modality

- VABB or CNB?

- No. of samples

- range

Event-free survival

IBTR

distant metastasis

Overall survival

QoL, Cost

Clip insertion protocol

Pathologic

Interpretation

pCR definition

- ypT0

- no ypTis

Biospecimen

collection

Biospecimen

collection

cCR evaluation

- MRI, USG

Korean Breast Cancer Study Group (KBCSG)

Aggressive TumorEffective systemic and targeted therapy

Less local treatment

Indolent TumorAppropriate local treatment

Less systemic therapy

SurgeryDong-Young NohWonshik HanHyeong-Gon MoonEun-Shin LeeYumi KimJiyoung RhuKyoung Eun KimJung Hyun ParkYoung Wook Ju

RadiologyWoo Kyung MoonNariya ChoJung Min ChangSu Hyun LeeSung Ui ShinSoo-Yeon Kim

PathologyIn-Ae ParkHan Suk RyuJung Ho Kim

OncologySeock-Ah ImTae-Yong KimKyung-Hun LeeMiso Kim

Patients and Family- Hee-Un Kim

Korean Breast Cancer Study Group (KBCSG)