Ductal Carcinoma In Situ (DCIS)

1. 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

2. 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?

3. Pathobiologic Events Associated with DCIS Burstein H et al. N Engl J Med 2004;350:1430-1441

4. DCIS: Pathology Cribiform, High grade Comedo Solid, Low grade Rosen’s Breast Pathology, 1997

5. DCIS: actin Stain of Myoepithelium Rosen’s Breast Pathology, 1997

6. SEER Breast Carcinoma in situ5-year Survival : 1992-1999

7. Survival DCIS: RCT

8. 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

9. Role of Total Mastectomy

10. 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 1-2% of all patients, irrespective of surgery type

11. 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

12. Oxford Overview of Randomized Trials of BCS±RT for DCIS Presented NIH DCIS Conference, 2009 Darby, JNCI Monograph, 2010

13. ECOG STUDY E5194 (n = 670) Registration of small DCIS after wide excision alone Negative margin width > 3 mm Tamoxifen optionalTwo arms (not randomized) Grade 1-2, non-comedo, size < 2.5 cm Grade 3, comedo, size < 1.0 cm

14. Ipsilateral (43 events/ 572 cases) Contralateral (18 events/ 572 cases) 0.15 6% 0.05 4% 0.0 0 2 4 6 8 ECOG E5194: EXCISION WITHOUT RADIATION (+/-TAM) High grade Low or intermediate grade 15% Year Hughes, JCO, 2009

15. LOCAL FAILURE ACCORDING TO PATHOLOGY Lumpectomy plus radiation Lumpectomy alone Solin, JCO, 1996 Slide courtesy of L. Solin Balleine, Clin Cancer Res, 2008

16. DCIS: NSABP B-24Role of Tamoxifen Fisher, B, Lancet 353:1993-2000, 1999

17. DCIS: NSABP B-24Median follow-up 7 years Fisher, B et al, Semin Oncol 28:400-18, 2001

18. NSABP B-24: Conclusions • Tamoxifen decreases risk of breast cancer events by 40% • No difference in overall survival

19. 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

20. 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

21. 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)

22. 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

23. 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

24. Mammography is the current standard for detection of DCIS, MRI could help improve the ability to diagnose DCIS, especially in high-grade DCIS

25. DCIS: CalcificationsCannot be diagnosed as non-invasive with cytology Irregular clusters Branching (comedo)

26. MRI: Contrast required…..spatial resolution improves morphologic assessment Mass, heterogeneous and rim enhancement, spiculated margins DCIS consensus conference. C. Lehman

27. 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

28. 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.

29. KEY QUESTIONS FOR THE MANAGEMENT OF DCIS Courtesy of L. Solin 2010