Lumpectomy and radiation therapy for the treatment of intraductal breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-17

Authors: Fisher B, Dignam J, Wolmark N, Mamounas E, Costantino J, Poller W, Fisher ER, Wickerham DL, Deutsch M, Margolese R, Dimitrov N, Kavanah M.
Source:J Clin Oncol. 1998 Feb; 16(2): 441-52

Background

Intraductal carcinoma-in-situ of the breast, commonly referred to as DCIS, is a pathologic diagnosis that is occurring with increasing frequency in recent years. This apparent rise in incidence correlates with and reflects the more widespread use of mammography in today's society, particularly in the identification of early, localized DCIS that would have otherwise remained undetected on physical exam. Issues regarding appropriate management of patients with mammographically-detected DCIS include the outcomes with limited breast surgery (i.e.: lumpectomy) and the possible role of postoperative breast irradiation in achieving maximum disease control.

This study aimed to evaluate whether radiation therapy following lumpectomy for early localized DCIS had a benefit compared to lumpectomy alone.

Materials & Methods

• Eligible patients had DCIS detected either on physical exam or mammography.
• 818 eligible women entered between 10/1/85 and 12/31/90.
• All women underwent lumpectomy with "removal of the tumor and a sufficient amount of normal breast tissue so that specimen margins were histologically tumor-free".
• Randomized to ipsilateral breast irradiation (Arm 1, n=413) or no radiation (Arm 2, n=405).
• Patient stratification by age (< or > 49 yrs), tumor type (DCIS or DCIS + LCIS), method of detection, and whether or not axillary dissection was performed.
• Radiation delivered in 2 Gy fractions to total dose of 50 Gy, using ipsilateral tangent fields.
• Radiation started no later than 8 weeks after surgery.
• Study looked at event-free survival, with event defined as:
• • tissue biopsy-proven tumor at local/regional site detected post-lumpectomy
  • tumor at distant site based on clinical +/- radiographic +/- pathologic findings
  • presence of ipsilateral (IBT) or contralateral (CBT) breast tumors, regional or distant metastases, second primary tumor, or death without evidence of recurrent disease

Results

• Mean follow up = 90 months (67 to 130)
• Event-free survival @ 8 yrs significantly better in Arm 1 vs. Arm 2: 75% vs. 62% (p= 0.00003)
• Average annual incidence rate for all first events reduced by 43% in Arm 1 compared to Arm 2: 3.68 vs. 6.40 (p=0.00004)
• • rate of noninvasive cancer reduced by 47% (p=0.007)
  • rate of invasive cancer reduced by 71% (p<0.000005)
• Cumulative 8-yr incidence of any IBT = 12.1% with radiation vs. 26.8% without radiation
• • incidence of noninvasive IBT = 8.2% vs. 13.4%
  • incidence of invasive IBT = 3.9% vs. 13.4%
• Relative risk of failure 1.74 for Arm 2 compared to Arm 1
• Within Arm 1:
• • 91 first events, 47 were IBTs
• Within Arm 2:
• • 143 first events, 104 were IBTs
• Cumulative 8-yr incidence of all first events other than IBT was NOT significantly different in two arms: 12.5% vs. 11.0% (p=0.96)
• Overall, 14 breast cancer-related deaths: 10 in radiation group and 4 in surgery only group

Conclusions

This 8-year update of data collected under protocol NSABP B-17 continues to show a benefit to post-lumpectomy ipsilateral breast irradiation in the management of patients with localized, mammographically-detected DCIS. This benefit consists primarily of a reduction in cumulative incidence of ipsilateral breast tumors (IBTs), both invasive and noninvasive types. Of note, the reduction in incidence of invasive IBTs was greater than that of noninvasive IBTs, although both reductions were statistically significant. There was no significant difference observed in incidence of locoregional and distant events. Finally, the paper concludes that at the present time, there are not any reliable clinical or pathologic predictors of IBT recurrence following lumpectomy alone for DCIS. Until such discriminants are identified and available, the authors would support the use of postoperative radiation therapy for all patients with localized DCIS based on the results of this trial.