Ductal Carcinoma in situ: Is Radiation Needed?

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1 Ductal Carcinoma in situ: Is Radiation Needed? UCSF Postgraduate Course March 23, 2011 Maui, Kawaii E. Shelley Hwang MD, MPH Professor UCSF Department of Surgery UCSF Helen Diller Family Comprehensive Cancer Center

2 Only selectively!

3 Learning Objectives Understand epidemiologic considerations for DCIS Appreciate the role of MMG and MRI in the detection of DCIS Estimate the overall recurrence risk for DCIS and the impact RT can have on this risk Recognize that risk stratification tools can help determine which patients may safely avoid RT

4 DCIS is a prevalent disease Over 65,000 women were diagnosed with DCIS in : incidence rates for DCIS increasing at 5 times that for invasive cancer DCIS now comprises over 20% of all mammographically detected breast cancers Normal" Tissue" ADH" DCIS" Invasive" Cancer" American Cancer Society, Breast Cancer Facts and Figures,

5 Disease reservoir of DCIS 7 autopsy series examined the prevalence of breast cancer in women not known to have had breast cancer in life Invasive cancer 1.3% (0-1.8%) DCIS 8.9% (0-14.7%) Series reporting a higher level of scrutiny tended to discover more cases of cancer Welch HG, Ann Intern Med, 1997, 127:1023-8

6 25! 20! 15! 10! 5! 0! DCIS Increased as the Number of Mammography Machines Increased ο ο DCIS is an unintended consequence of increased screening United States Preventive Services Task Force now ο recommends against ο routine MMG screening in 1 in 1300 screening exams ο women <50 diagnose DCIS ο 1980! 1983! 1985! 1987! 1989! 1991! ο ο ο ο ο

7 Age-adjusted incidence rate of invasive breast cancer and in situ cancer for all females,

8 Invasive breast cancer incidence rate (per 100,000) Figure 4. Hypothetical invasive breast cancer incidence assuming DCIS progressed in absence of treatment SEER reported rate of invasive breast cancer 100% DCIS progresses 60% DCIS progresses 20% DCIS progresses SEER incidence rate is shown (solid thick line) as are hypothetical invasive cancer incidence trends assuming that 100% of DCIS had progressed to invasive cancer in absence of treatment (top solid line), 60% progressed (top dotted line), and 20% progressed (bottom dotted line). Ozanne E et al, unpublished

9 The Role of Mammography for DCIS Mammography/stereotactic biopsy remains the mainstay of detection and diagnosis for DCIS Majority of patients (90%) with DCIS have a mammographic abnormality Mammographic size can underestimate pathologic size, sometimes by as much as 2 cm Occult invasive cancer can be found in up to 20% of patients with DCIS alone on core biopsy

10 Evolving Role of MRI for DCIS Study of 51 women with DCIS only Majority of patients (72%) diagnosed by mammography MRI much more sensitive at detecting residual disease (97% vs. 81%), occult invasive cancer (86% vs. 14%), and multicentricity (94% vs. 38%) Hwang ES, Ann Surg Oncol 2003

11 MRI and Mastectomy Rates for DCIS Itakura K, Clin Breast Cancer 2010

12 Comparison of Mammography to MRI in High Risk Women 1952 high risk women followed median 2.9 years CBE q 6 months, MMG and MRI q 12 months 51 tumors found: 44 invasive cancer, 6 DCIS, 1 lymphoma Overall, MRI detected 32 cancers and missed 13 MMG detected 5/6 DCIS MRI only detected 1/6 DCIS Kriege M, NEJM, 351:427-37, 2004

13 Prevalence of BCS for DCIS Stratified by SEER Site, Joslyn SA, Breast J 2006

14 All Ipsilateral Events Postoperative Radiotherapy vs Lumpectomy Alone Overall, there was over a 50% reduction in ipsilateral events with radiation following lumpectomy This benefit was independent of patient age, tumor size, margin status Goodwin A, Cochrane Database Syst Rev, 2009.

15 All Ipsilateral Events Postoperative Radiotherapy vs Lumpectomy Alone Ipsilateral Invasive Events Ipsilateral DCIS Events Goodwin A, Cochrane Database Syst Rev, 2009.

16 Outcome: Determinants of Van Nuys Prognostic Index (VNPI) Factor Size <=15 mm mm >40 mm Margin >=10 mm 1-9 mm <1 mm Pathology neither comedo grade 3 Age >=60 years years <40 years Silverstein M, The Breast, 2003, 12:457-71

17 DCIS Outcome by VNPI Retrospective analysis of patients undergoing lumpectomy without radiation for DCIS. Outcome was highly correlated with VNPI. Silverstein M, The Breast, 2003, 12:457-71

18 Ipsilateral and Contralateral Breast Events E5194 High grade DCIS Low/Intermediate grade DCIS % for high grade (35% invasive) - 6.1% for low/int grade (53% invasive) Hughes LL, et al., JCO 2009

19 age <45 FH mode of dx RT Tam gr 1 vs 2/3 necrosis margins # excisions Rudloff U et al. JCO 2010

20 Nomogram for predicting 5- and 10-year probability of ipsilateral breast tumor recurrences (IBTR) after breast-conserving surgery for ductal carcinoma in situ. Rudloff U et al. JCO 2010

21 Type of Recurrence can be Predicted by Baseline Biomarkers IBC Risk DCIS Risk Kerlikowske K, JNCI 2010

22 Trial Schema: DCIS treatment stratified by risk of invasive cancer

23 Summary DCIS is a prevalent disease primarily treated by lumpectomy Mammography is the mainstay for diagnosis; MRI is best used in a clinical trial setting for DCIS The optimal use of adjuvant radiation therapy is being increasingly tailored to patient and disease factors Indications for excision alone are being expanded, and will be supported by increasing use of biomarkers in future trial designs for DCIS

24 Mahalo!