Effect of radiotherapy on survival of women with locally excised ductal carcinoma in situ of the breast: a Surveillance, Epidemiology, and End Results population-based analysis

Background: Although it has been previously reported that radiotherapy (RT) effectively reduced the incidence of local recurrence of ductal carcinoma in situ (DCIS) following breast-conserving surgery (BCS), little is known about the effect of RT on survival of patients with locally excised DCIS.
Patients and methods: Using Surveillance, Epidemiology, and End Results registry data, we selected 56,968 female DCIS patients treated with BCS between 1998 and 2007. Overall survival (OS) and breast cancer-specific survival (BCSS) were compared among patients who received RT or no RT using the Kaplan–Meier methods and Cox proportional hazards regression models.
Results: Median follow-up was 91 months. In the multivariable model, patients receiving postoperative RT had better OS than those undergoing BCS alone (hazard ratio [HR] 0.59, 95% confidence interval [CI] 0.53–0.67, P<0.001). This pattern remained after stratification by estrogen receptor (ER) status and age. In contrast, RT delivery was not significantly associated with improved BCSS (HR 0.71, 95% CI 0.48–1.03, P=0.073). However, after stratifying by the above two variables, RT contributed to better BCSS in ER-negative/borderline patients (HR 0.41, 95% CI 0.19–0.88,P=0.023) and younger patients (≤50 years old; HR 0.37, 95% CI 0.15–0.91, P=0.030).
Conclusion: Our analysis confirms the beneficial effect of RT on OS in women with locally excised DCIS and reveals the specific protective effect of RT on BCSS in ER-negative/borderline and younger patients.

Keywords: ductal carcinoma in situ, breast cancer, breast-conserving surgery, radiotherapy, survival

INTRODUCTION

Ductal carcinoma in situ (DCIS) is defined as a premalignant condition that involves proliferation of neoplastic mammary ductal epithelial cells without evidence of invasion beyond the basement membrane.¹ Until the 1980s, mastectomy remained the reference treatment for patients with DCIS. However, with the introduction of breast-conserving surgery (BCS) for the treatment of early-stage breast cancer, local excision of DCIS began to be widely adopted. Currently, BCS has become the most common surgery for DCIS, constituting 74% of treated cases according to a query of the Surveillance, Epidemiology, and End Results (SEER) database.² In addition, radiotherapy (RT) has become one of the main types of adjuvant therapy for DCIS.³

To date, four randomized controlled trials (RCTs) have investigated the effectiveness of RT in reducing local recurrence (LR) of DCIS after BCS.^4–7 All four trials confirmed that postoperative RT reduced in situ or invasive recurrences by approximately 50%. However, long-term results of the NSABP B-17 trial showed that RT was not associated with overall mortality reduction.⁸ In addition, the EORTC and SweDCIS trials showed that the long-term prognosis of DCIS was not influenced by RT.^9,10

Nevertheless, only two trials took survival as a study endpoint.^9,10 In the SweDCIS trial, there existed a potential positive selection bias in determining the cause of death; the authors only retrieved the medical records of women with a previous ipsilateral or contralateral event.¹⁰ In the EORTC trial, there existed misclassification in the pathological assessments of the cases; 5% and 3% of the lesions were reclassified as benign disease and microinvasive carcinoma, respectively.¹¹ The sample size of the aforementioned single trial was relatively small. The publication of data from the four RCTs did not settle the ongoing debates regarding the pros and cons of RT following BCS for DCIS treatment.

Therefore, we performed this SEER population-based analysis to investigate the effect of RT on survival of DCIS patients who had undergone BCS with or without postoperative RT, aiming to provide some evidence to assist clinical decision-making in the management of DCIS.