Five year results of Intergroup Study E5194: local excision alone (without radiation treatment) for selected patients with ductal carcinoma in situ (DCIS)

Reviewer: John P. Plastaras, MD, PhD
The Abramson Cancer Center of the University of Pennsylvania
Last Modified: December 16, 2006

Presenter: L. Hughes
Affiliation: Eastern Cooperative Oncology Group


  • Based on results of large randomized trials studying adjuvant treatment for excised ductal carcinoma in situ, adjuvant breast radiation is the gold standard to reduce the risk of local recurrence
  • Retrospective analyses have attempted to identify favorable subsets of patients that gain little additional benefit of adjuvant radiotherapy
  • This is the first prospective study of local excision alone for DCIS


  • 711 patients with DCIS were enrolled in this prospective Intergroup (ECOG and North Central Cancer Treatment Group (NCCTG)) trial
  • Patients were enrolled from 1997 to 2002
  • The protocol was amended in 2000 to allow for adjuvant tamoxifen when the NSABP B-24 showed a benefit of adjuvant tamoxifen in DCIS
    • 31% of patients opted to take tamoxifen
  • Two cohorts were eligible, both required at least 3 mm of DCIS:
    • Low/Intermediate Grade DCIS, < 2.5 cm
    • High Grade DCIS, < 1 cm
      • Nuclear Grade 3 plus necrosis over 2 mm
  • Margins: >/- 3 mm
  • Post-excision mammography had to be negative if there were initially calcifications
  • A unique aspect of this study was that the entire specimen had to be embedded to accurately assess pathologic criteria
    • all pathology was centrally reviewed by David Page at Vanderbilt University
    • recurrences also required central review
  • Endpoint: local recurrence rate


  • Of the 711 patients enrolled, 31 were ineligible, mostly due to lack of criteria for a diagnosis of DCIS and inadequate margins
  • When the target enrollment for the Low/Intermediate cohort was reached (606 patients), enrollment into the High Grade cohort was also terminated due to poor accrual (105 patients)
  • Median age was 60 years. Median f/u was 5.4 years.
  • Low/Intermediate Grade cohort:
    • median size: 6 mm. 82% were < 1 cm.
    • Margins: 67% had at least 5 mm margin. 46% had at least 10 mm margin or a negative re-excision
    • 5 year recurrence rates:
      • Ipsilateral breast: 6.1% (95% CI: 4.0-8.2%)
      • Contralateral breast: 3.7%
    • 50% of the recurrences were invasive, 50% were DCIS
    • Overall survival: 96%
    • Relapse free survival: 85%
  • High Grade cohort:
    • median size: 7 mm
    • Margins: 75% had at least 5 mm margin. 48% had at least 10 mm margin or a negative re-excision
    • 5 year recurrence rates:
      • Ipsilateral breast: 14.8%
      • Contralateral breast: 4.2%
    • 50% of the recurrences were invasive, 50% were DCIS
    • Overall survival: 98%
    • Relapse free survival: 79%

Author's Conclusions

  • In carefully selected patients with low or intermediate grade DCIS, the local recurrence rate without adjuvant radiation was acceptable
  • In high grade DCIS, the recurrence rate was unacceptably high without adjuvant radiation

Clinical/Scientific Implications

  • This study is important because it is the first prospective study of omitting radiotherapy in patients with DCIS with suspected to risk of recurrence
  • Depending on a patient's tolerance for local recurrence, omission of radiotherapy may be considered after complete excision of low or intermediate grade DCIS.
  • Even in the low/intermediate grade patients, there may be certain high risk prognostic factors that would favor use of adjuvant radiotherapy. Analysis of this trial continues, including the impact of tamoxifen use, margin width, and nuclear grade 3 in the absence of necrosis. Perhaps the most important question remaining will be the success rate of salvage treatment after failure.