1. Dilemma in management of DCIS
Julia Tchou, M.D., Ph.D.
Abramson Cancer Center
Rena Rowan Breast Center
Department of Surgery
University of Pennsylvania

2. 96-98% of women with DCIS are cured with local therapy, yet …
The Dilemma of DCIS
96-98% of women with DCIS are cured with local therapy, yet …
Local recurrence rate after BCT of DCIS is ~ 2 fold higher than Invasive cancer.
When I see patients in clinic, I often told my patients that it is counterintuitive to think of DCIS having a higher local recurrence rate than when we are treating invasive cancer.
Local recurrence rate after BCT 3-4% in 5 years (Solin MRI paper in JCO)
But the local recurrence rate is around 5 – 9 % in 5 years of DCIS
Why?
I think we should improve risk stratification

3. Standard Treatment in DCIS
• Mastectomy
• Excision + RT
• Excision
+ Tamoxifen
The need for adding RT after excision to maintain locla control in patients with DCIS has remained uncertain. (Harris J and Morrow 2009)
Which Rx for which patient?

4. Key questions in management of DCIS
Can we identify a subset of patient not benefiting from radiation therapy?
What is an adequate margin?
Leaving out other questions
Is Sentinel node biopsy necessary
When is mastectomy indicated
Is partial breast radiation ready for prime time?

5. Survival in DCIS by Treatment
L+RT
B17
L+RT+TAM
EORTC M
B17; EORTC
% Deaths Breast Ca
Prognosis is extremely good whether the woman has undergone lumpectomy alone vs. lumpectomy with radiation (yellow lines). The NSABP B17 results are almost superimposable with the results of the european DCIS trial.
Breast cancer death ranges from 0.5 to 3% not significantly different
European Organixation for resarch and treatment of cancer EORTC
EORTC 10853, Randomized controll trial women 10 year follow up, LE local excisiom 503 vs LE + RT 507, no boost, , margins not free < = 1 mm
4.4 % death rate median FU 10 years
10 year LR for LE 26%, LE with RT 15%,
B17 LE +/- RT, 8 year follow up, LE 403, LE + RT 411
B24
B24
Years

6. Effects of XRT on survival
However, survival beniefit for radiation after excision in patients with invasive breast cancer has clearly established as It is hard not to extrapolate the survival benefit after excision of invasive cancerof XRT (Morrow M 2009 JCO)
EBCTCG meta-analsyis, Lancet 2005

7. Key Management Concepts in DCIS
Prevention of local recurrence (invasive and noninvasive) is a major goal of the treatment of DCIS
The use of RT reduces LR in DCIS

8. Can we identify a subset of patient not benefiting from RT?

9. Can DCIS be treated by excision alone?
Study
LE alone
LE + XRT
Tamoxifen use
Margins
IBT rate
NSABP B-17, 1998
403
411 no
free
27% vs. 12% at 8 years
UK Trial, 2003
508
522
yes
20 % vs. 10% at 5 years
EORTC 10853, 2006
503
507
26% vs. 15% at 10 years
Harvard, 2006
158
1 cm
12% at 5 years
ECOG, 2009
565
3 mm
6.1% vs. 15% (5 year rate)
3 randomized control trials to look at whether DCIS can be treated by excision alone showed that local recurrence rate is significantly higher.
NSABP Fisher F JCO 1998
UK trial: Lancet 2003 (estimate LR rate from Figure 4)
European EORTC Bijker N 2006
2 subsequent and contemporary trials (prospective, single arm) looked at the local recurrence rate in low risk DCIS, less than 2.5 cm with good margins but
Harvard: Wong JS JCO 2006, trial expected to accrue 200 patients but stopped early as the IBT recurrence rate has exceeded the stopping boundary 8 local recurrence in 200 patients. DCIS needs to be less than 2.5 cm with grade 1 or 2 DCIS. Necrosis is not a factor for exclusion. Patient may be undergoing first excision from another hospital and then re-excision – pathology assessment may not be as complete.
ECOG: Hughes LL JCO 2006: median f/u of 6.2 years, ECOG only includes DCIS less than 2.5 cm stratified by low/intermediate grade vs. high grade
2 cohorts – low or intermdiate histologic grade DCIS 2.5 cm or smaller; the second consisted of high grade DCIS 1 cm or smaller. The surgical specimen were serially sectioned and completely embedded at the trating institution to determin size grade and margins. Central path review by david page.

10. Local recurrence risk stratification
ECOG – < 2.5 cm Grade I & II DCIS
EORTC – no subgroup does not benefit from radiation
VNPI - Silverstein
The EuropeanThere is not a subgroup that does not benefit from RT
Bijker, N. JCO 2006;24:3381

11. Van Nuys Prognostic Index
Silverstein, M 2003

12. Local recurrence free survival
Silverstein M 2003

13. Outcome in DCIS Patients with Low VNPI
Low VNPI (3 or 4)
Silverstein de Mascarel
# patients
Local recurrence 2% 9%
Invasive %
Br Ca Res Treat 2000
The very low recurrence rate seen by Silverstein is not duplicated in other study. Retrospective analysis of 195 cases of DCIS using the pathology assessment VNPI
Median f/u in this French study (Bordeaux) 71 months. ( ) the specimen was sectioned every 2 mm and embedded enirely

14. Is there a DCIS subgroup that does not benefit from XRT?
Age
Margins (uniform and meticulous assessment not done in randomized trials)
VNPI score 4, 5 or 6
Low grade DCIS
Biomarkers for risk stratification
Utility of MRI in preoperative assessment (JNCI consensus statement, 2009)
Morrow M 2008