Transcript Locoregional management and neoadjuvant systemic treatment Birgit Carly MD Breast Unit Isala Breast Cancer Prevention Center CHU Saint Pierre Brussels.

Locoregional management
and
neoadjuvant systemic treatment
Birgit Carly MD
Breast Unit
Isala Breast Cancer Prevention Center
CHU Saint Pierre
Brussels
Inoperable Breast Cancer
(LABC and IBC)
Neoadjuvant CT
-
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
Operable Breast Cancer
Neoadjuvant CT vs adjuvant CT
NSABP -B18
n
chimio
OS
chir conserv(%)
1523
AC (4)
id
67 vs 60
37 vs 21
60%T2, 13%T3
EORTC 10902
698
FEC (4)
id
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?
Correct cTNM to establish first treatment: surgery or systemic treatment
After NAC: Clinical Response Tumor through Change Size, Change Nodal Status
Tools: - Breast: Physical Examination, Mammography, Ultrasound, MRI
- Axilla: Physical examination, US, SN?
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?
No NAC
After NAC
NAC: degeneration,
necrosis, fibrosis, sclerosis,
inflammation of the Tumor
Chagpar AB, Ann Surg 2006
Staging Breast Tumor
after NAC
162 pat, retrosp.
Accuracy
43 pat, retrosp.
Accuracy pCR
Phys Ex
53%
Phys Ex
75%
Mx + US
67%
Mx
89%
PE + Mx + US
63%
US
82%
MRI
89%
Peintinger F, Ann Surg Oncol 2006
Schott A, Breast Cancer Research and Treatment, 2005
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.
Multidetector-row CT, PET, H MR spectroscopy
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 Cancer
NSAPB-B27
GEPARDUO
(GABG)
Penault-Llorca
(France)
Buzdar (Houston)
Smith (Scottish)
n
chimio
cCR
(%)
pCR
(%)
BCR
(%)
2411
AC (4)
40
9,8
61
AC (4), DOC (4)
65
18,7
63
A Pacl (4) / 2w
32,5
7,7
65
AC (4), DOC (4)
57,4
16,1
75
AC
6
45
A Pacl
15
56
913
200
174
104
FAC (4)
24
18
35
Pacl (4)
27
6
46
CVAP (8)
33
15,4
48
CVAP (4), DOC
(4)
56
30,8
67
B.C.
Operable Breast Cancer
Neoadjuvant 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 Cancer
Neoadjuvant CT and BCT
340 patients NAC, Stage I 4%, Stage II 58%, Stage III 38%
Medium FU 60 months
29 (95%)Local regional recurrence with 16 (91%) ipsilateral breast tumor
recurrence
Variables positive correlation:
- Clinical N2 or N3
- Pathological residual tumor larger then 2 cm
- Multifocal pattern
- Lymphovascular space invasion
Chen AM J Clin Oncol 2004
Role of type of surgery on LR,
risk factors
1772 women, breast cancer stade I-II,
randomised (EORTC et DBCG), retrospective
Local recurrence
Distant metastasis
10% at 10 yrs 9% at 10 yrs
BCT + MRM
Vascular Invasion
BCT:
BCT + MRM
Tumor size
Nodal Status
Age < 35 yrs
High histological grade
Extended DCIS
Vascular Invasion
Voogd A, J Clin Oncol 2001
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?
Feasibility of SN mapping before NAC in cN0?
Feasibility of FU lymphatic mapping after NAC?
Can patients be spared Axillary Clearance post NAC?
Schrenk P Am J Surg 2008
Which Surgery to the Axilla.
SN as definitive treatment before
NAC when SN negative?
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
Schrenk P Am J Surg 2008
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-27
Neoadjuvant CT for Early Breast Cancer
AC +/- docetaxel
SN after NAC
- Succes rate 84.8%
- 98.9% SN in axilla
- 36.4% N+
- False Neg Rate 10.7%
Only to offer when pCR in breast
2411women, 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
Optimal integration of SNB into
neoadjuvant chemotherapy
program
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
33/104 patients Lymphoscintigraphy
before and after NAC: same image on
lymphoscintigraphy
Kinoshita T, Breast Cancer 2007
SNB after NAC in N + patients at diagnosis.
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?