Locoregional management Locoregional management and and

neoadjuvant systemic treatmentneoadjuvant systemic treatment

Birgit Carly MD

Breast Unit Isala Breast Cancer Prevention Center

CHU Saint PierreBrussels

Inoperable Breast CancerInoperable Breast Cancer(LABC and IBC)(LABC and IBC)

- Standard of care

- Clinical downstaging T and N status

- Makes surgery possible

- Allows BCT

- Complete Pathologic response of primary T and axillary N is a prognostic factor

- Better overall survival

Machiavelli MR, Cancer J Sci Am 1998 / Ferriere JP, Am J Clin Oncol 1998 / Cance WG, Ann Surg 2002

Neoadjuvant CT

Operable Breast CancerOperable Breast CancerNeoadjuvant CT vs adjuvant CTNeoadjuvant CT vs adjuvant CT

n chimio OS chir conserv(%)

NSABP -B18 152360%T2, 13%T3

AC (4) id 67 vs 60

EORTC 10902 698 FEC (4) id 37 vs 21

ABCSG trial 7 423 CMF (3)

+ CMF or EC adj

id

Scholl 390 FAC (4) id 82 vs 77

- BCT possible without compromising survival;- Pathologic Complete Response better outcome;- Can be used to study Breast Cancer Biology;- Same DFS and OS.

Questions NAC and Locoregional treatment

• Optimal Method for Staging at Diagnosis and Evaluation Clinical Response after NAC?

•Use Sentinel Node?

• How to mark the tumorbed?

• Which Surgery in the Breast and the Axilla?

• Which Chemotherapy

•Timing of Surgery?

Staging at diagnosis and after NAC: optimal method

At diagnosis: Size, Unifocality, Type, Grading, Hormone Receptor status, Neu / HER2, Ki67, Contralateral breast, Nodal Status.

Tools: - Breast: Physical Examination, Mammography, Ultrasound, Microbiopsy. MRI?

- Axilla: Physical Examination, US, FNA, SN?

After NAC: Clinical Response Tumor through Change Size, Change Nodal Status

Tools: - Breast: Physical Examination, Mammography, Ultrasound, MRI - Axilla: Physical examination, US, SN?

Correct cTNM to establish first treatment: surgery or systemic treatment

Correct yTNM to establish surgery : Conservatice surgery vs mastectomy

Which staging we use after NAC for completing treatment, cTNM and / or yTNM:implications in surgery and RT

Staging at diagnosis and after NAC: optimal Imaging method

Breast?

NAC: degeneration, necrosis, fibrosis, sclerosis, inflammation of the Tumor

Chagpar AB, Ann Surg 2006

No NAC After NAC

Staging Breast Tumor after NAC

Peintinger F, Ann Surg Oncol 2006

Schott A, Breast Cancer Research and Treatment, 2005

Multidetector-row CT, PET, H MR spectroscopy

162 pat, retrosp. Accuracy

Phys Ex 53%

Mx + US 67%

PE + Mx + US 63%

43 pat, retrosp. Accuracy pCR

Phys Ex 75%

Mx 89%

US 82%

MRI 89%

Good overall correlation between MRI and Overall response, but very bad correlation when pCR.

Biopsy after NAC remains absolutely necessary to determine pCR

Type of Tumor important in measurement of residual tumor: lobular underestimated, poorly differentiated overestimated.

How to mark the tumorbed?

-Titanium clip in the center of the tumor before NAC

- Tattoo with black coal in center or at 4 poles of tumor

Neoadjuvant CT for Early Breast CancerNeoadjuvant CT for Early Breast Cancer

B.C.

n chimio cCR (%)

pCR (%)

BCR (%)

NSAPB-B27 2411 AC (4) 40 9,8 61

AC (4), DOC (4) 65 18,7 63

GEPARDUO (GABG)

913 A Pacl (4) / 2w 32,5 7,7 65

AC (4), DOC (4) 57,4 16,1 75

Penault-Llorca (France)

200 AC 6 45

A Pacl 15 56

Buzdar (Houston) 174 FAC (4) 24 18 35

Pacl (4) 27 6 46

Smith (Scottish) 104 CVAP (8) 33 15,4 48

CVAP (4), DOC (4)

56 30,8 67

Operable Breast CancerOperable Breast CancerNeoadjuvant CT and BCTNeoadjuvant CT and BCT

Breast conservation after NAC yields no higher incidence of positive margins than primary surgical treatment.

Soucy G J Am Coll Surg 2007

NAC equivalent to adjuvant CT for survival and DFS.

NAC increased risk of locoregional recurrence when RT without surgery was adopted.

Mauri D J Natl Cancer Inst 2005

Operable Breast CancerOperable Breast CancerNeoadjuvant CT and BCTNeoadjuvant CT and BCT

340 patients NAC, Stage I 4%, Stage II 58%, Stage III 38%Medium FU 60 months29 (95%)Local regional recurrence with 16 (91%) ipsilateral breast tumor recurrence

Chen AM J Clin Oncol 2004

Variables positive correlation:

- Clinical N2 or N3

- Pathological residual tumor larger then 2 cm

- Multifocal pattern

- Lymphovascular space invasion

Role of type of surgery on LR, risk factors

1772 women, breast cancer stade I-II,

randomised (EORTC et DBCG), retrospective

Voogd A, J Clin Oncol 2001

BCT:

Age < 35 yrs

Extended DCIS

Local recurrence10% at 10 yrs 9% at 10 yrs

Tumor size

Nodal Status

High histological grade

Vascular Invasion

BCT + MRM

Vascular Invasion

Distant metastasis

BCT + MRM

Axilla: Staging at diagnosis.

Khan A Surg Oncol 2005; Kilbride KE Ann Surg Oncol 2008; Grube BJ Arch Surg 2008;

Which Surgery to the Axilla. Optimal integration of SNB into

neoadjuvant chemotherapy program

Kilbride KE Ann Surg Oncol 2008; Khan A Ann Surg Oncol 2005; Grube BJ Arch Surg 2008;

Which Surgery to the Axilla. SN as definitive treatment before

NAC when SN negative?

Schrenk P Am J Surg 2008

Feasibility of SN mapping before NAC in cN0?

Feasibility of FU lymphatic mapping after NAC?

Can patients be spared Axillary Clearance post NAC?

Which Surgery to the Axilla. SN as definitive treatment before

NAC when SN negative?

Schrenk P Am J Surg 2008

45 cT2T3N0 (PE, US)

Pre NAC: SN IR 100%; 19 SN0, 26 SN+ ( 6/26 micromet)

After NAC all axillary cleareance:

SN IR 64%: - 80% SN0 or micromet pre NAC

- 45% SN+ pre NAC

FNR 0% N0 pre NAC

50% N+ pre NAC

Which Surgery to the Axilla. SN as definitive treatment before

NAC when SN negative?

Grube BJ Arch Surg 2008

Optimal integration of SNB into neoadjuvant chemotherapy

program.SN Post NAC

Grube BJ Arch Surg 2008

NSABP B-27NSABP B-27Neoadjuvant CT for Early Breast CancerNeoadjuvant CT for Early Breast Cancer

AC +/- docetaxelAC +/- docetaxelSN after NACSN after NAC

2411women2411women, T1c-3, operable, palpable, N0-1

428 lymphatic mapping after NAC was attempted

Primary enpoint: Identification Rate, False Neg. Rate

Mamounas E, J Clin Oncol 2005

- Succes rate 84.8%

- 98.9% SN in axilla

- 36.4% N+

- False Neg Rate 10.7%

Only to offer when pCR in breast

Optimal integration of SNB into neoadjuvant chemotherapy

program

33/104 patients Lymphoscintigraphy before and after NAC: same image on

lymphoscintigraphy

Kinoshita T, Breast Cancer 2007

Questions:

•Does tumour response to NAC causes lymphatic scarring that could affect drainage pattern?

•Does NAC has the same effect on involved SN as it does on non-involved SN

SNB after NAC in N + patients at diagnosis.SNB after NAC in N + patients at diagnosis.Can downstaging prevent Axillary dissection?Can downstaging prevent Axillary dissection?

Retrospective, 69patients, N+ at diagnosis by US FNA, mean T 4 cm

IR 92.8%, FN 25%

Shen J, Cancer 2007

Retrospective, 54 patients, N+ at diagnosis by US FNS or SNB, mean T 3 cm;

IR 98%, FN 8.6%

Newman E, Annals of Surgical Oncology 2006

Optimal integration of SNB into neoadjuvant chemotherapy

program

It is prognostically valuable to differentiate patients who presented as node negative from those who were

downstaged by chemotherapy

Which systemic neoadjuvant treatment ?

Chemotherapy or Endocrine treatment.

Same treatment that reflects state of the art in adjuvant regimens.

Timing of Surgery All CT upfront or Split CT by Surgery?

- The ideal timing of surgery, when NAC is given, is not known. - Treatment plan should be devised at the start and should

not be altered until there is clear evidence of disease progression.

- Patients with disease progression during initial course of treatment should be switched to alternate regimen or offered local therapy. - Use of additional CT after standard course of CT with residual tumour has no proven benefit.

Questions NAC and Locoregional treatment

• Optimal Method for Staging at Diagnosis and Evaluation Clinical Response after NAC?

•Use Sentinel Node?• How to mark the tumorbed?

• Which Surgery in the Breast and the Axilla?• Which Chemotherapy

•Timing of Surgery?