1. 18th Annual Perspectives in Breast Cancer
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

2. Controversies in DCIS Management
Is nipple sparing mastectomy appropriate?
Is RT necessary for all DCIS?
When is SN biopsy indicated?
What about endocrine rx?

3. 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% ( %)
Skin sparing mastectomy n = 223
Local recurrence 3.1%
Boyages J, Cancer 1999;85:616
Carlson G, JACS 2007;204:1074

4. 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.

5. 10/26/2011

6. 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
# Cases
772
162
5yr LR
Breast
3.6%
4.9%
NAC
0.8%
2.9%
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

7. 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.

8. What do I really think about NSM?
It’s a great operation for a woman
who doesn’t actually need a mastectomy.

9. Is RT Necessary for All DCIS?

10. Randomized Trials of Excision ± RT
in DCIS
Trial
# Patients
% Mammo Detected
Boost
Tamoxifen
NSABP B17
813 80 No
EORTC 10853
1002 71
UK/ANZ
1030
100
Yes
Swedish
1046 78

11. Metaanalysis Trials of Excision ± RT
in DCIS
n = 3729
10 yr IBTR
No RT RT
p-value
Total
28.1%
12.9%
< .001
Invasive
15.4%
6.8%
DCIS
14.9%
6.5%
EBCTCG JNCI Monograph 2010;41:162

12. Metaanalysis Trials of Excision ± RT
in DCIS
10 yr Survival Outcomes
No RT RT
p-value
All deaths
8.2
8.4
> .1
Death w/o recurrence
5.7
5.4
Cardiac death
1.3
1.5
EBCTCG JNCI Monograph 2010;41:162

13. Conclusions of Randomized Trials
RT reduces the risk of LR by 50%.
Patient subsets NOT benefitting from RT have not been identified.

14. Academic U.S. Physicians Recommending RT For DCIS
Ceilley E, Cancer 2004;101:1958

15. 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.

16. Does wide excision + detailed pathology exam
result in local control equivalent to excision + RT?

17. Local Recurrence: Margins ≥ 10 mm
Silverstein M, NEJM 1999;340:1455

18. 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

19. Patient Characteristics: E5194
Low/Int Grade
High Grade
Number
579
101
Median Size
6mm
7mm
Margin ≥ 1cm
46%
48%
Margin ≥ 5mm
67%
75%
TAM planned
31%
Hughes L, J Clin Oncol 2009;27:5319

20. Intergroup Trial of Excision Alone
Mean f/u 6.3 years
High Grade
Low Grade
IBTR
5yr
15.3%
6.1%
7yr
18.0% ( )
10.5% ( )
Contralateral
3.9%
3.7%
7.4% ( )
4.8% ( )
Hughes L, J Clin Oncol 2009;27:5319

21. Local Failure According to Pathology After Lumpectomy and Radiation
Solin L, J Clin Oncol 1996;14:754

22. 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

23. 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

24. RTOG 9084 Schema RANDOMIZE Observation RT No Boost 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
RANDOMIZE
Observation RT
No Boost

25. Patient Characteristics: RTOG 9084
Observation RT
Number
298
287
Median Age 58
Mammographic size < 1 cm
72.8%
72.1%
Grade 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%
McCormick B, ASCO 2012

26. Local Failure Ipsilateral Breast
5-Years Rates:
3.2%
0.4%

27. Local Recurrence After Excision +/- RT in Good Prognosis DCIS
5 yr LR
Excision Alone
Excision + RT
E5194
RTOG 9084
6.1%
3.2%
0.4%
Hughes L, J Clin Oncol 2009;27:5319
McCormick B, ASCO 2012

28. Conclusions E 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.

29. 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 E 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) San Antonio Breast Cancer Symposium

30. 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

31. 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.

32. 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

33. Risk of Axillary Recurrence in DCIS
Treatment years
Rate/1000 pt
Lumpectomy Only
0.76
L+XRT B17
0.86
L+XRT B24
0.49
L+XRT+TAM
0.46
Julian, Ann Surg Oncol 2006

34. 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.

35. Benefit of Tamoxifen in ER+ DCIS
NSABP B n = 732 HR
p-value
Any Breast Cancer Event
0.58
.0015
Any Invasive Cancer
0.53
.005
Contralateral Cancer
0.50
.02
Allred DC, J Clin Oncol 2012;30:

36. Other Therapies in DCIS
• Exemestane
MAP 3 — 112 of 4560 had DCIS
HR 0.47 (95% CI, )
No subset analysis
Data on other AIs coming from NSABP B35, IBIS II
Raloxifene
Equivalent to tamoxifen in STAR overall, better side- effect profile
DCIS analysis RR 1.46 (95% CI, )
Goss PE, NEJM 2011;364:
Vogel VJ, JNCI Monogr 2010:181-6

37. 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.