Memorial Sloan-Kettering Cancer Center
1275 York Avenue, New York, NY 10065
18th Annual Perspectives in Breast Cancer
New York, NY
18 August 2012
Treatment Decision Making for DCIS
Monica Morrow MD
Chief, Breast Surgery Service
Anne Burnett Windfohr Chair of Clinical Oncology
Memorial Sloan-Kettering Cancer Center
Controversies in DCIS Management
• Is nipple sparing mastectomy appropriate?
• Is RT necessary for all DCIS?
• When is SN biopsy indicated?
• What about endocrine rx?
Mastectomy in DCIS
• Indicated when DCIS is too extensive to be
encompassed with a cosmetic resection.
• Outcome
Metaanalysis 21 studies, 1574 patients
Local recurrence 1.4% (0.7-2.1%)
Skin sparing mastectomy n = 223
Local recurrence 3.1%
Boyages J, Cancer 1999;85:616
Carlson G, JACS 2007;204:1074
What About
Nipple Sparing Mastectomy?
Concerns
•
NSM leaves behind ductal tissue + breast tissue
in order to preserve blood supply.
•
Occult nipple involvement present in 6-31% of
cancers.
•
Most studies of NSM are in invasive cancer.
10/26/2011
Clinical Outcomes NSM
European Institute of Oncology 3/02-12/07
Median f/u: 50 months
All patients received 16 Gy to NAC
Invasive Cancer
DCIS
772
162
Breast
3.6%
4.9%
NAC
0.8%
2.9%
# Cases
5yr LR
CAUTION: At 20 mo f/u, no NAC recurrences, 1.4% LR
Petit JY, Ann Oncol 2012;23:2053-8
Petit JY, Br Ca Res Treat 2009;117:333
NSM in DCIS
• Increased risk of LR due to retained breast tissue
and poor exposure.
• Contraindicated in patients with extensive DCIS
necessitating mastectomy, localized DCIS in
subareolar space.
What do I really think about NSM?
It’s a great operation for a woman
who doesn’t actually need a mastectomy.
Is RT Necessary for All DCIS?
Randomized Trials of Excision ± RT
in DCIS
Trial
NSABP B17
EORTC
10853
UK/ANZ
Swedish
# Patients
% Mammo
Detected
Boost
Tamoxifen
813
1002
80
71
No
No
No
No
1030
100
No
Yes
1046
78
No
No
Metaanalysis Trials of Excision ± RT
in DCIS
n = 3729
10 yr IBTR
Total
Invasive
DCIS
No RT
RT
p-value
28.1%
15.4%
14.9%
12.9%
6.8%
6.5%
< .001
< .001
< .001
EBCTCG JNCI Monograph 2010;41:162
Metaanalysis Trials of Excision ± RT
in DCIS
10 yr Survival Outcomes
All deaths
Death w/o recurrence
Cardiac death
EBCTCG JNCI Monograph 2010;41:162
No RT
RT
p-value
8.2
5.7
1.3
8.4
5.4
1.5
> .1
> .1
> .1
Conclusions of Randomized Trials
• RT reduces the risk of LR by 50%.
• Patient subsets NOT benefitting from RT have not
been identified.
Academic U.S. Physicians
Recommending RT For DCIS
Ceilley E, Cancer 2004;101:1958
Concerns Regarding Randomized Trials
• Detailed tissue processing/method of pathology
evaluation not specified.
• Post-excision mammography not mandated.
• Impact of margin width on RT benefit not assessed.
Does wide excision + detailed pathology exam
result in local control equivalent to excision + RT?
Local Recurrence: Margins ≥ 10 mm
Silverstein M, NEJM 1999;340:1455
E5194: Excision Alone ± Tamoxifen
for DCIS Eligibility
• DCIS ≥ 3mm in size
• Minimum margin width ≥ 3mm
• Specimen completely embedded, sequentially
sectioned
• Post-excision mammogram free of calcification
Hughes L, J Clin Oncol 2009;27:5319
Patient Characteristics: E5194
Low/Int Grade
High Grade
Number
579
101
Median Size
Margin ≥ 1cm
Margin ≥ 5mm
TAM planned
6mm
46%
67%
31%
7mm
48%
75%
31%
Hughes L, J Clin Oncol 2009;27:5319
Intergroup Trial of Excision Alone
Mean f/u 6.3 years
High Grade
Low Grade
5yr
15.3%
6.1%
7yr
18.0% (10.2-25.9)
10.5% (7.5-13.6)
5yr
3.9%
3.7%
7yr
7.4% (1.4-13.5)
4.8% (2.7-6.9)
IBTR
Contralateral
Hughes L, J Clin Oncol 2009;27:5319
Local Failure According to Pathology
After Lumpectomy and Radiation
Solin L, J Clin Oncol 1996;14:754
Effect of Margin Width – No RT
Intergroup Trial
% Local Recurrence
Margin
Low Grade
High Grade
< 1cm
5.6
14.8
≥ 1cm
6.7
15.9
Hughes L, J Clin Oncol 2009;27:5319
RTOG 9084: RT vs Observation
for “Good Risk” DCIS
Eligibility
•
•
•
•
Mammographic or incidental DCIS
Low or intermediate grade
Size (mammographic) ≤ 2.5 cm
Margins ≥ 3 mm
McCormick B, ASCO 2012
RTOG 9084 Schema
Stratify
Age
< 50
≥ 50
Margins
Negative re-excision
3-9 mm
≥ 10 mm
Size
≤ 1 cm
> 1 cm-2.5 cm
Grade
Low
Intermediate
Tamoxifen
No
Yes
R
A
N
D
O
M
I
Z
E
Observation
RT
No Boost
Patient Characteristics: RTOG 9084
Observation
RT
Number
298
287
Median Age
58
58
72.8%
72.1%
44%
42.2%
Margin
3-9 mm
≥ 10 mm
Neg. re-excision
35.6%
16.1%
48.3%
36.2%
15.7%
48.1%
Intent to use Tam
Yes
69.5%
68.6%
Mammographic size < 1 cm
Grade 1
McCormick B, ASCO 2012
Local Failure Ipsilateral Breast
30
FailedTotal
Observation 15 298
2 287
RT
Local Failure (%)
25
20
Gray's test p-value=0.0022
HR =
0.14 (0.03,0.61)
15
10
5-Years Rates:
3.2%
5
0.4%
0
0
Patients at Risk
Observation 298
RT
287
2
4
Years after Randomization
272
264
232
228
6
147
141
Local Recurrence After Excision +/- RT
in Good Prognosis DCIS
5 yr LR
Excision Alone
E5194
6.1%
RTOG 9084
3.2%
Hughes L, J Clin Oncol 2009;27:5319
McCormick B, ASCO 2012
Excision + RT
RTOG 9084
0.4%
Conclusions E5194 + RTOG 9084
• Rates of LR after excision alone differed
significantly among 2 populations with “favorable”
DCIS selected with standard histopathologic
criteria.
• Benefit for RT is present even in this good-risk
subset.
A QUANTITATIVE MULTIGENE RT-PCR ASSAY FOR
PREDICTING RECURRENCE RISK AFTER SURGICAL
EXCISION ALONE WITHOUT IRRADIATION FOR DUCTAL
CARCINOMA IN SITU (DCIS): A PROSPECTIVE VALIDATION
STUDY OF THE DCIS SCORE FROM ECOG E5194
Solin LJ, Gray R, Baehner FL, Butler S, Badve S, Yoshizawa C,
Shak S, Hughes L, Sledge G, Davidson N, Perez EA, Ingle J,
Sparano J, Wood W
Eastern Cooperative Oncology Group (ECOG)
North Central Cancer Treatment Group (NCCTG)
Genomic Health, Inc (GHI)
2011 San Antonio Breast Cancer Symposium
DCIS Recurrence Score:
Unanswered Questions
• Do patients in the low-risk group benefit from RT?
Is it predictive as well as prognostic?
• Does it apply to the wider population of women
with DCIS?
• Validation needed
Sentinel Node Biopsy in DCIS
• DCIS lacks the ability to metastasize.
• Rationale for axillary surgery is risk of unsampled
invasive cancer.
• ~15% risk of invasion after core bx diagnosis of
DCIS.
Risk of Axillary Recurrence in DCIS
NSABP B17: 7 of 623 pts with axillary recurrence
1 s/p axillary dissection
3 with invasive IBTR
3 of 620 with DCIS at 15 yrs
NSABP B24: 6 of 1799 pts at 11.6 yrs
1 with undiagnosed microinvasion
Julian, Ann Surg Oncol 2006
Risk of Axillary Recurrence in DCIS
Treatment years
Lumpectomy Only
L+XRT B17
L+XRT B24
L+XRT+TAM
Julian, Ann Surg Oncol 2006
Rate/1000 pt
0.76
0.86
0.49
0.46
When Should Axillary Nodes
Be Examined in DCIS?
• Microinvasive carcinoma
Metastases in 3% - 20% of cases.
• DCIS treated by mastectomy.
Opportunity lost if invasion found.
• Done as a second procedure if invasion found
after lumpectomy.
Prior biopsy does not interfere with mapping.
Benefit of Tamoxifen in ER+ DCIS
NSABP B24
n = 732
Any Breast Cancer Event
Any Invasive Cancer
HR
0.58
0.53
p-value
.0015
.005
Contralateral Cancer
0.50
.02
Allred DC, J Clin Oncol 2012;30:1268-73
Other Therapies in DCIS
•
Exemestane
MAP 3 — 112 of 4560 had DCIS
HR 0.47 (95% CI, 0.27-0.79)
No subset analysis
•
Data on other AIs coming from NSABP B35, IBIS II
•
Raloxifene
Equivalent to tamoxifen in STAR overall, better sideeffect profile
DCIS analysis RR 1.46 (95% CI, 0.90-2.41)
Goss PE, NEJM 2011;364:2381-91
Vogel VJ, JNCI Monogr 2010:181-6
Conclusions: Endocrine Rx
• Endocrine therapy is an option for women
desiring to minimize future breast cancer events.
• Most favorable risk-benefit ratio is in
premenopausal women with 2 breasts.