Transcript Predicting Breast Cancer Risk

Management of the Axilla in Patients
Receiving
Neoadjuvant Chemotherapy (neoCTX)
for Breast Cancer
Lisa A. Newman, M.D., M.P.H., F.A.C.S.
Professor of Surgery
Director, Breast Care Center
University of Michigan
Ann Arbor, MI
Expanding BCS Eligibility:
Neoadjuvant Systemic Therapy
CTX Effect on Primary Tumor
Preop vs Postop CTX:
Randomized Trials
Study
Stg
BCS
F/U
Pre
LR after BCS
Overall
Survival
Post
Pre
Post
Pre
Post
Institut
Curie
2-3 66 m 82%
77%
24%
18%
86%
78%
Royal
Mars
1-3 48 m 89%
78%
3%
4%
80%
80%
NSABP
1-3 108 m 68%
B18
60%
10.7%
7.6%
69%
70%
Surgical Staging of the Axilla
Axillary Lymph Node Dissection
•Morbidity: Lymphedema,
Numbness, Shoulder dysfunction
Lymphatic Mapping & SLN Bx
•Alternative surgical staging
strategy; minimizes risks of axillary
surgery without compromising
staging/treatment
•Goal: Replicate pathway of cancer
cells from primary tumor to initial
draining axillary lymph node(s)
Is SLN Bx Compatible with Neoadjuvant CTX Protocols?
Should it be performed pre-; post-; or pre- and post-CTX?
•What happens to
intramammary lymphatics
as the primary breast tumor
enlarges?
•Does chemotherapy have a
uniform effect on all
axillary nodal metastases?
•Does chemotherapy alter
lymphatic drainage
patterns?
SLN ACCURACY IN
T2/T3 TUMORS
• What happens to intramammary lymphatics as the
primary breast tumor enlarges?
Are SLN non-identification and false negative rates
higher in cases of bulky breast tumors?
Study
Tumor
Year
Size
N
Findings
ID Rate FN Rate
Bedrosian 2000  2 cm
104
99%
3% (2/61)
2001  5 cm
41
100%
3% (1/31)
Chung
CTX EFFECT ON AXILLARY
METASTASES
• Inferential Evidence:
Decreased rates of node-positive disease in pts
treated with neoadjuvant CTX
• NSABP B-18
• Direct Evidence:
Studies of pts with node-pos disease
(documented by sono-guided FNA Bx) treated
with neoadjuvant CTX:
 23-33% converted to node-negative status on
post-CTX axillary lymph node dissection
• Newman et al, Ann Surg Onc 2002
• Rouzier et al, JCO 2002
• Kuerer et al, Ann Surg 1999
SLN BX AFTER
NEOADJUVANT CTX
Study
N
ID
FN
Mets Limited to SLN
Breslin 2000
51
85%
12%
40%
Nason 2000
15
87%
33%
NR
Haid 2001
33
88%
0%
50%
Tafra 2001
29
93%
0%
NR
Julian 2002
34
91%
0%
42%
Miller 2002
35
86%
0%
44%
Brady 2002
14
93%
0%
60%
Piato 2003
42
98%
17%
0%
Balch 2003
32
97%
5%
56%
Schwartz 2003
21
100%
9%
64%
Reitsamer 2003
30
87%
7%
53%
Mamounas 2005
428
85%
11%
50%
Tanaka 2006
70
90%
5%
42%
SLN BX PRIOR TO
NEOADJUVANT CTX
Pre-CTX
Study
N
SLN
ID
Post-CTX
SLN +
ALND
performed
ALND neg (%)
Zirngibl
2002
15
93%
43%
Only SLN+
100%
Sabel
2003
24
100%
42%
Only SLN+
30%
All pts
12 SLN-neg pts:
100%
10 SLN-pos pts:
60%
Olilla
2003
22
100%
45%
ADVANTAGES OF PRE-neoCTX
VS. POST-neoCTX SLN BX
Following neoCTX
•
Pro •
•
Con •
Before neoCTX
More data on results of
•
SLN Bx performed after
neoadjuvant CTX delivered
Surgical sequence
•
consistent with
conventional neoadjuvant
•
regimen
Significance of nodal status
better understood when axillary
staging performed at diagnosis
Preferred by many medical and
radiation oncologists
More surgical experience with
SLN Bx in the pre-CTX setting
•
? Unnecessary ALND’s
- metastatic disease limited to
the excised SLN in 30-50%
- CTX sterilizes 25-30% nodepos pts
Requires additional surgery
False negative rates not yet
optimized
- range, 0-40%
Significant learning curve
•
UNIVERSITY OF MICHIGAN
NEOCTX PROGRAM
Comprehensive pre- and postNeoadjuvant CTX axillary evaluation
• Baseline axillary ultrasound
– With sono-guided FNA-Bx of any suspicious nodes
• Baseline SLN Bx in sono-neg pts
• After completion of neoCTX:
– Pre-CTX node-neg pts → → No further axillary surgery
– Pre-CTX node-pos pts → → SLN Bx + cALND
Rationale for SLN Bx after Negative Axillary
Ultrasound: Risk of False Negative Imaging
• University of Michigan
• Growney et al, SSO 2009
–121 node-positive cases
–Nodal mets documented by
sono FNA in 88 (73%) and
by SLN biopsy in 33 (27%)
–Follow-up SLN necessary
for accurate staging in
ultrasound-negative cases
UM Approach to NeoCTX and
Axillary Staging
Pre- and post-CTX staging allows
stratification of pts into 3 distinct categories
–Pts presenting with node-neg disease
–Pts presenting with node-pos disease,
downstaged to pN-0
–Pts presenting with node-pos disease that is
chemoresistant
Is it necessary to document the pathologic
axillary status prior to delivery of
neoadjuvant chemotherapy?
NSABP B-18:
Patterns of Locoregional Failure
Operable Breast Cancer
Stratification
• Age
• Clinical Tumor Size
• Clinical Nodal Status
Surgery
AC x 4
AC x 4
Surgery
Neoadjuvant vs. Adjuvant AC
–Stages I-III
–Lumpectomy patients received
breast XRT
–Mastectomy patients received
no chest wall or regional XRT
Tamoxifen X 5 years for pts
> 50 after completion of chemo
Fisher B. et al: JCO 1997, JCO 1998;
Wolmark N. et al: JNCI 2001
NSABP B-18:
PREDICTORS OF LRF
B-18 Data suggest that
post-CTX nodal status
is reliable indicator of
pts likely to benefit from
locoregional or
postmastectomy XRT
However:
-Small sample size of post-CTX node-negative cases
-Unknown: LRF rates among pts that started out
pathologically node-negative compared to those that
were downstaged to node-negativity
UM Neoadjuvant CTX Experience
• N= 161 neoadjuvant chemotherapy cases
• Median age at diagnosis 49 years
Mean tumor size at presentation 45.0 mm
• Median follow-up 38.1 months
• Relapse rate at median follow-up 21.7%
–35 patients
–17 Local Recurrences
–28 Distant Recurrences
Kilbride et al, Ann Surg Onc 2008
Outcome by
Axillary Lymph Node Response
Lymph Node
Response
n
Any
Relapse
LocoReg
Recurrence
Distant
Recurrence
Node-Negative at
Presentation
37
(23%)
13.5%
8.1%
8.1%
Downstaged to
Node-Negative
36
(23%)
19.4%
5.6%
13.9%
Persistently
Positive
86
(54%)
25.6%
14.0%
22.1%
0.13
0.21
0.05
P value
Use of regional radiation (PMRT or
breast + nodal fields) in downstaged group
12.5%
p=0.33
3.6%
UM Approach to NeoCTX and
Axillary Staging
• Pre- and post-CTX staging allows stratification of
pts into 3 distinct categories
– Pts presenting with node-neg disease
– Pts presenting as node-pos, downstaged to pN-0
– Pts presenting as node-pos disease, chemoresistant
• Sequential use of lymphatic mapping offers
promise of minimizing number of cases subjected
to ALND
UM: 54 Cases of Node-Pos Breast Cancer
Undergoing SLN Bx & Completion ALND after
Neoadjuvant CTX
Nonidentification of
post-CTX SLN in
1/54 cases (2%)
Final Nodal Status
n = 53
Remained node positive
36/53 (68%)
Positive SLN
33/36 (92%)
False negative
3/36 (8%)
Newman E et al
Ann Surg Onc 2007
No residual disease
17/53 (32%)
Limited to SLN
12/36 (33%)
The Future:
Abandon
completion
ALND in
cases with a
neg post-CTX
SLN
ACOSOG Z1071 Study Schema
Phase II Study Evaluating the Role of Sentinel
Lymph Node Surgery and Axillary Lymph Node
Dissection Following Preoperative Chemotherapy in
Women with Node Positive Breast Cancer
Accrual Target: 550 patients
Summary
• Neoadjuvant chemotherapy (neoCTX) improves
eligibility for breast-conserving surgery
• Optimal strategy for integrating lymphatic
mapping and neoadjuvant CTX remains undefined
– Accuracy of sentinel lymph node biopsy not yet
optimally-defined when performed after neoCTX
– SLN biopsy prior to neoCTX requires additional
surgical procedure and anesthetic exposure
• Combination of pre- and post- neoCTX axillary
staging provides maximal information regarding
CTX response and is important for planning XRT
University of Michigan Health Center
MUCHAS GRACIAS POR SU ATENCION!!!!