Ductal Carcinoma In Situ (DCIS)
JoAnne Zujewski, MD
Head, Breast Cancer Therapeutics
Clinical Investigations Branch
Cancer Therapy Evaluation Program
Division of Cancer Diagnostics and Treatment
May 2011
Questions
• How DCIS differs from Stage 1 breast
cancer
• Types of DCIS that affect prognosis of
DCIS/development of breast cancer
• Standard of Care: surgery, radiation
risks of under-treatment and
overtreatment
• Can we improve diagnosis through MRI
and sentinel lymph node biopsy?
Pathobiologic Events Associated with DCIS
Burstein H et al. N Engl J Med 2004;350:1430-1441
DCIS: Pathology
Comedo
Rosen’s Breast Pathology, 1997
Solid,
Low grade
Cribiform,
High grade
DCIS: actin Stain of
Myoepithelium
Rosen’s Breast Pathology, 1997
SEER Breast Carcinoma in situ
5-year Survival : 1992-1999
All
< 50
50+
All
100.0
99.9
100.0
White
100.0
100.0
100.0
Black
100.0
99.5
100.0
Survival DCIS: RCT
N
Mets
NSABP
B17
EORTC
813
1002
UKANZ NSABP
B24
CTG
1694
1798
17
24
(2.1%) (2.4%)
Breast 27
15
23
Deaths (3.3%) (1.5%) (1.4%)
Years
10.8
4.3
4.4
F/up
11
(0.6%)
15
(0.8%)
6.9
Natural History
• 25 cases untreated with 16 yrs follow
up
– 28% developed invasive cancer
– 11 fold increase in relative risk to
controls
• Contralateral relative risk 2-3
Page et al Cancer 1985;55:2698-708
Role of Total Mastectomy
Year
No.
cases
%
mortality
Ashikari
1971
182
0.9
Rosner
1980
182
2.0
Farrow
1970
181
2.0
Silverstein
1996
228
0
Bradley
1990
588
1.7
Surgery
• Mastectomy has not been compared to
BCT in randomized trials of DCIS
• Breast cancer deaths within 10 years
after the diagnosis of DCIS occurs in 12% of all patients, irrespective of
surgery type
RATIONALE FOR RADIATION TREATMENT
AFTER LUMPECTOMY FOR DCIS
• All reported randomized trials show that radiation
reduces the rate of local recurrence after
lumpectomy by about half
• “[P]atients who may avoid radiation therapy have
not been reproducibly and reliably identified by any
clinical trials.” (1999 DCIS Consensus Conference
Statement, Cancer, 2000)
Slide courtesy of L. Solin
Oxford Overview of Randomized Trials of BCS±RT
for DCIS
DCIS: BCS + RT vs. BCS
Ips. BREAST RECURRENCE (CIS & Inv)
5-year gain 10.5 % (SE 1.2)
10-year gain 15.2 % (SE 1.6)
logrank 2p < 0.001
50
40
30
18.1
20
10
60
5-year gain 5.4 % (SE 0.8)
10-year gain 8.5 % (SE 1.3)
logrank 2p < 0.001
50
40
BCS
28.1%
30
20
BCS+RT
12.9%
8.5
10
3723 women
5-year gain 5.8 % (SE 0.9)
10-year gain 8.4 % (SE 1.2)
logrank 2p < 0.001
50
40
30
20
BCS
15.4%
BCS
14.9%
10.5
10
BCS+RT
6.8%
7.6
0
0
0
DCIS: BCS + RT vs. BCS
Ips. BREAST RECURRENCE (CIS only)
3723 women
Ips. BREAST RECURRENCE (CIS only) (%)
60
3723 women
Ips. BREAST RECURRENCE (Inv only) (%)
60
DCIS: BCS + RT vs. BCS
Ips. BREAST RECURRENCE (Inv only)
5
10
Years since randomisation
15
17:41:28 9 Sep 2009
Provisional results: subject to revision
(Name: gr_cis_sc_rt_rlili_all_0)
0
BCS+RT
6.5%
4.7
0
3.1
5
10
Years since randomisation
15
17:42:03 9 Sep 2009
Provisional results: subject to revision
(Name: gr_cis_sc_rt_rlilii_all_0)
0
5
10
Years since randomisation
15
17:42:38 9 Sep 2009
Provisional results: subject to revision
(Name: gr_cis_sc_rt_rllic_all_0)
Presented NIH DCIS Conference, 2009
Darby, JNCI Monograph, 2010
ECOG STUDY E5194 (n = 670)
Registration of small DCIS after wide excision alone
Negative margin width > 3 mm
Tamoxifen optional
Two arms (not randomized)
Grade 1-2, non-comedo, size < 2.5 cm
Grade 3, comedo, size < 1.0 cm
Low/intermediate grade
Tumor size (median)
6 mm
Negative margin width
>5mm
>10mm
Hughes, JCO, 2009
69.2%
48.5%
High grade
5 mm
82.9%
53.3%
ECOG E5194: EXCISION WITHOUT RADIATION (+/-TAM)
0.15
15%
0.05
High grade
Low or intermediate grade
Ipsilateral (43 events/ 572 cases)
Contralateral (18 events/ 572 cases)
6%
0.0
4%
0
2
4
6
8
Year
Hughes, JCO, 2009
LOCAL FAILURE ACCORDING TO PATHOLOGY
Lumpectomy plus radiation
Lumpectomy alone
Solin, JCO, 1996
Slide courtesy of L. Solin
Balleine, Clin Cancer Res, 2008
DCIS: NSABP B-24
Role of Tamoxifen
Fisher, B, Lancet 353:1993-2000, 1999
DCIS: NSABP B-24
Median follow-up 7 years
placebo
tamoxifen
Pvalue
All breast
cancer
145
16%
84
9.3%
ipsilateral
100
11.1%
72
7.7%
0.02
Contralateral
45
4.9%
25
2.3%
0.01
survival
95%
95%
Fisher, B et al, Semin Oncol 28:400-18, 2001
NSABP B-24: Conclusions
• Tamoxifen decreases risk of breast
cancer events by 40%
• No difference in overall survival
The Risk of Ipsilateral or Contralateral Breast Tumor for Patients with DCIS Treated
with Excision Alone; Excision and Radiotherapy; Excision, Radiotherapy, and
Tamoxifen; or Excision, Radiotherapy, and Placebo
Burstein H et al. N Engl J Med 2004;350:1430-1441
DCIS: Conclusions
• Local therapy
– Mastectomy
– Breast Conserving Surgery plus
radiotherapy
• Consider omission if
– Short lifespan
– Sever co-morbidities
• Systemic therapy: Tamoxifen
– “Prevention” intervention
– Consider individual risk/benefits
What about lymph nodes?
• Axillary lymph node involvement is
<1% therefore axillary lymph node
dissection is not recommended
• Sentinel lymph node biopsy?
– Not recommended due to low risk of
disease unless performing a mastectomy
(in the chance that invasive disease is
found)
– Consider: extensive high grade DCIS or
palpable mass (increased chance of
invasive disease being found)
Potential Benefits
• SLNB at time of definitive surgery
avoids 2nd operation in 2-21 % of
patients who have IDC at
definitive surgery
• May identify subset of patients
who would benefit from systemic
therapy
Risks of SLNB in DCIS
• Increase anxiety: curable prognosis to
one that is life-threatening
• SLNB risks
– infection, bleeding, seroma, paresthesias,
anaphylaxis, lymphedema (3%)
• Risks of full ALND in up to 13%
• Risks of systemic chemotherapy ?
• Public health costs
Mammography is the current standard
for detection of DCIS, MRI could help
improve the ability to diagnose DCIS,
especially in high-grade DCIS
DCIS: Calcifications
Cannot be diagnosed as non-invasive with
cytology
Irregular
clusters
Branching (comedo)
MRI: Contrast required…..spatial resolution
improves morphologic assessment
Mass, heterogeneous and rim
enhancement, spiculated margins
DCIS consensus conference. C. Lehman
DCIS diagnosed in high risk patient on screening MRI
with negative screening mammogram
Fine linear, branching NMLE in ductal distribution
DCIS consensus conference. C. Lehman
ACR-ASS-CAP-SSO 2006 practice
guideline
• The role of other image modalities, especially MRI,
has yet to be established in DCIS.
• Berg found that MRI was more sensitive than
mammography and sonography in detecting DCIS;
however, disease extent was overestimated in 50%
of involved breasts.
• The impact of MRI on clinical outcomes such as
local recurrence in the preserved breast remains to
be demonstrated.
KEY QUESTIONS FOR THE MANAGEMENT OF DCIS
Answers
1. Is there a subgroup of patients for which the
risk of local recurrence is low enough that the
risk/benefit ratio warrants omission of radiation?
Probably
2. If so, can one identify reproducibly and
prospectively that subgroup of patients for
treatment with excision alone (without radiation)?
No
3. After lumpectomy, should (almost) all
patients receive maximal treatment to reduce the
risk of local recurrence?
- Radiation
- Tamoxifen, if ER/PR positive
Yes
Yes
Courtesy of L. Solin 2010