52_trad 05

Three prospective randomized studies of excision only versus excision plus breast irradiation for DCIS have been performed, and all have shown that the rate of local recurrence was reduced with the addition of radiation (Table 52.1). The NSABP B-17 trial (41,43) consisted of 818 patients who were stratified by age (49 years of age or younger vs. older than 49 years), DCIS versus DCIS plus LCIS, method of detection, and whether an axillary dissection was performed. Tumor size was determined by mammogram, gross pathologic measurement, or clinical examination. Of the patients enrolled, 83% had nonpalpable tumors. The 12-year rate of local recurrence was 15.7% with radiation and 31.7% without radiation (p <.000005) (Fig. 52.6). The average annual incidence rates of all ipsilateral breast tumor recurrences, ipsilateral noninvasive recurrences, and ipsilateral invasive recurrences were reduced with breast irradiation by 59%, 47%, and 71%, respectively. An analysis of clinical variables showed that microcalcifications extending beyond a maximum dimension of >1 cm were associated with an elevated risk of breast recurrence. A central pathology review was performed, including a multivariate analysis of histopathologic variables (Table 52.2), that revealed only moderate/marked comedonecrosis as being significantly associated with local failure risk. Margin status (free vs. unknown/involved) was of borderline significance.


The EORTC 10853 trial (14,67) randomly allocated 1,010 patients with 5 cm or smaller DCIS and negative margins to excision versus excision plus breast irradiation. Lesions were nonpalpable in 79% of patients, and the mean maximal tumor diameter was approximately 2 cm. The 10-year rate of local recurrence was 15% for patients treated with radiation, as compared with 25% for patients treated without radiation (p <.0001). At a median follow-up of 10.2 years, radiation therapy resulted in risk reduction for both invasive and noninvasive breast relapse of 42%. As with the NSABP B-17 study, a central pathology review was performed (14,15). In a multivariate analysis (Table 52.3), factors associated with an increased risk of local recurrence were age 40 years or younger, clinically symptomatic presentation (nipple discharge or palpable mass), intermediate or poorly differentiated DCIS, solid and cribriform histologic growth pattern, involved or uncertain margins, and treatment by local excision alone. The risk of invasive recurrence was not related to histologic type of DCIS, but the risk of distant metastasis was significantly higher in poorly differentiated DCIS compared with well-differentiated DCIS.

The EORTC 10853 trial did not allow the identification of an appropriate margin width for treatment with or without radiotherapy because the eligibility criteria did not require reporting of the margin status. Nonetheless, the central review of cases did provide some information regarding the relative importance of surgical margin as related to local failure risk. A recurrence rate of 24% at 4 years was observed in cases with close/involved margins after excision alone. Radiotherapy was not adequate to compensate for involved margins because even with the application of irradiation the recurrence rate was 20% in this group. These data and others (108,109,116,117) are strongly suggestive that obtaining a microscopic complete excision is essential for optimal local control in breast-conserving therapy for DCIS. Of further note, even in the group of DCIS cases for which margins could be considered optimal (i.e., those patients who underwent a surgical re-excision in which no residual DCIS was found), a 4-year local recurrence rate of 18% was observed when these patients were treated with surgery alone (15).


The UKCCCR DCIS Working group has also conducted a randomized trial investigating the role of adjuvant radiotherapy (59). With a 2 × 2 factorial protocol design, the aim of this study was to compare excision alone versus excision plus tamoxifen versus excision plus radiotherapy versus excision plus radiotherapy and tamoxifen. Tamoxifen was prescribed as 20 mg per day and radiotherapy was delivered through whole-breast tangential fields to a total dose of 50 Gy. Boost was not recommended. A total of 1,030 patients were enrolled. When reported with 4.38 year follow-up, the crude incidence of local recurrence was 14% of the patients who were treated with excision only and 6% when the excision was followed by radiotherapy. The addition of tamoxifen offered no benefit toward overall ipsilateral local control when administered in addition to radiotherapy; however, tamoxifen did appear to reduce the ipsilateral recurrence rate of DCIS (but not invasive carcinoma) in the absence of radiotherapy (59).

Subgroup analyses from randomized trials have demonstrated that the absolute benefits of radiotherapy are greater in women at increased risk for tumor recurrence, such as women with involved surgical margins (identified on retrospective pathologic review), younger women, and those with tumors that have high-grade or comedonecrotic features (14,15,41,43). However, radiotherapy lowers the incidence of recurrence among all subgroups, regardless of the baseline risk.