American College of Surgeons Oncology Group Z11 Update

American College of Surgeons
Oncology Group Z11 Update
Dennis R. Holmes, M.D.
Breast Cancer Surgeon
Medical Director
Los Angeles Center for Women’s Health
Susan Boyle
Britain’s Got Talent
I Dreamed A Dream
American College of Surgeons
Oncology Group (ACOSOG)
Z11 Update
February 8, 2011
Lymph Node Study Shakes Pillar of
Breast Cancer Care
•  “…for Node + women
who meet certain
criteria, taking out
cancer nodes has no
advantage.”
…impact 40,000
women a year in the
U.S.
ACOSOG Z0011
165 Investigators / 115 Institutions
Guiliano A et al. JAMA. 2011;305(6):569-575.
Z11
Take Home Message
•  ALND was unnecessary in women
with 1 or 2 positive sentinel nodes
if they were initially clinically
node negative, and if they planned
to be treated with lumpectomy
and Whole Breast Radiotherapy
Axillary Stage
Key Prognostic Factor
•  Axillary Metastasis
–  Presence
–  Extent
•  Influences
–  Extent of surgery
–  Chemotherapy
–  Radiation therapy
Complete Axillary Lymph Node
Dissection
Axillary LN Dissection
Halsted Radical Mastectomy
Courtesy M. Silverstein
Level I, II, III ALND (All Patients)
I
II
III
Pectoralis
Minor
Level I, II ALND (All Patients)
I
II
Pectoralis
Minor
Sentinel Node (Clinically Node - Only)
I
Pectoralis
Minor
Tracers:
1. Blue Dye
2. Blue Dye
3. Radioactive
Level I, II ALND
(Clinically or Sentinel Node Positive)
I
II
Pectoralis
Minor
ACOSOG Z11
Central Questions Do BCT Candidates with positive
sentinel nodes require ALND?
Does omitting ALND after a positive
sentinel node biopsy diminish
patient survival?
NSABP B-04 Trial
Does Axillary Node Dissection Effect
Overall Survival in Mastectomy Pts?
Initiated in 1971
Operable Breast Cancer
Clinically
Node-Negative
Radical
Mastectomy
I,Ii,III ALND
Total
Mastectomy
Clinically
Node-Positive
Total
Mastectomy
+ Irradiation
Radical
Mastectomy
Total
Mastectomy
+ Irradiation
No Systemic Therapy
N Engl J Med 2002;347:567-575
NSABP B-04
Overall Survival—Clinically
Negative Nodes
100
80
%
60
RM
362
259
TMR
352
274
TM
365
259
40
20
0
P=NS
0
5
10
15
20
25
Years
N Engl J Med 2002;347:567-575
Radical Surgery Unnecessary
ALND
Sentinel node biopsy
And Breast Radiotherapy
ACOSOG Z0011
165 Investigators / 115 Institutions
Guiliano A et al. JAMA. 2011;305(6):569-575.
Z0011 Study Design Schema
N=856
5/99 – 12/04
Patient and Tumor
Characteristics
Intent-to-treat
SLND
ALND
n = 420
n = 436
Median age
Clinical T1
ER+
PR+
LVI present
56 (24-92)
68%
83%
68%
41%
54 (25-90)
71%
83%
70%
36%
P = N.S.
Inclusion/Exclusion Criteria
Eligibility
•  Clinical T1, T2, N0 breast
cancer
•  H&E-detected metastases
in SN (AJCC 5th edition),
N1
•  Lumpectomy with whole
breast irradiation|
•  Adjuvant systemic
therapy by choice
Ineligibility
•  Third field (nodal),
irradiation
–  Matted node
–  Extracapsular extension
–  3 or more involved nodes
•  Metastases in SN
detected by IHC only, N0
Adjuvant Systemic Therapy
ALND
SLND
Chemotherapy
57.9%
58.0%
Hormonal therapy
46.4%
46.6%
Either/Both
96.0%
97.0%
P = N.S.
Median Number of
Lymph Nodes Removed
# of Positive Lymph Nodes
Intent-to-Treat Analysis
Residual Axillary Nodal Disease
21% of pts.
had additional
positive nodes
ALND
~21% of pts.
expected
to have residual
positive nodes
SN only
ACOSOG Z11
What is the significance of retained
axillary disease in the SN-only group?
Would it lead to increased axillary
recurrences?
Would it decrease overall survival
(1° endpoint) and disease free survival
(2° endpoint)?
Locoregional Recurrences
Median Fu: 6.3 years
Intent-to-Treat
Recurrence
ALND
(420 pts)
SLND
(436 pts)
Local (Breast)
15 (3.6%)
8 (1.8%)
2 (0.5%)
4 (0.9%)
Regional (*)
Total Locoregional 17 (4.1%)
12 (2.8%)
P = 0.11
*Regional (Axillary, Supraclav, Subclav, Internal Mammary)
Tangent Fields used to
Treat the Preserved Breast
.
.
.
Breast Fields Also Treat The
Low Axilla
Three clips at
SLND site
Wire showing
palpable breast
borders
Tumor bed
Axillary Failure Is
Uncommon after AxRT
5-Year Survival Outcomes
ACOSOG Z11
DFS
(Secondary)
OS
(Primary)
ALND
82.2%
91.8%
SN
83.9%
92.5%
p = 0.14
p = 0.25
ACOSOG Z11’s Conclusion
SNB alone provides excellent
locoregional control,
comparable to SNB with completion
ALND,
in patients with T1 or T2 breast
cancers with 1-2 +SN treated
by
whole breast radiotherapy and
adjuvant systemic therapy.
ACOSOG Z11
Surgical Morbidity
Lucci A et al. J Clin Oncol. 2007 Aug 20;25(24):3657-63
Implications
Implications
Systemic Therapy
Systemic Rx decisions are
based on tumor features
–  Receptor status
–  Oncotype DX/Mammaprint
–  Adjuvant Online!
–  Not number of nodes
Implications
Systemic & Radiotherapy
•  Residual positive nodes remaining in the
axilla after SNB are adequately treated with
systemic therapy and axillary radiation.
Implications
Preoperative Axillary US
Implications
•  Z11 results cannot be extrapolated to
patients
–  Treated with mastectomy;
–  with 3 or more positive, ECE, matted nodes;
–  with grossly positive nodes;
–  having partial breast radiation
–  Neoadjuvant chemotherapy/endocrine tx
Implications
Reduced Morbidity
Chronic Pain
(5-10%)
Lymphedema
(10-15%)
Axillary Web
(30-50%)
Improved QOL
Improved QOL
ACOSOG 11 Summary
•  Z11 contributes to a paradigm shift
•  Reduces extent of Axillary Surgery
•  Reduces morbidity of axillary surgery
•  Improve patient QOL
•  Without compromising DFS and OS
reducing the morbidity of axillary staging!
⌃