Is Excision Alone Adequate Treatment for Low-Risk Ductal Carcinoma-in-Situ of the Breast?

The diagnosis of ductal carcinoma-in-situ (DCIS; intraductal carcinoma) of the breast presents a dilemma for both the patient and the treating physician. DCIS is a nonobligate precursor of invasive carcinoma and occupies a position on the spectrum of neoplasia between benign and malignant. Some patients with DCIS will develop a true malignancy over time, but some patients will not, and current prognostic capabilities cannot predict the natural history for individual patients. When DCIS is diagnosed, patients and physicians often pursue treatment in an attempt to prevent a subsequent malignant lesion from developing because malignant transformation carries well-known risks for the patient from invasive carcinoma. Treatment with radiation and tamoxifen can reduce the risk of recurrence, including invasive recurrence, but for the overall population of patients with DCIS, such risk reduction comes with the knowledge that the majority of patients are overtreated. Compounding this dilemma, most DCIS lesions are detected in asymptomatic patients on routine screening mammography, and virtually no patient dies from an index DCIS lesion. Can some patients with DCIS be adequately treated with excision alone? One of the major clinical questions surrounding the management of DCIS is whether there is an identifiable cohort of patients with sufficiently low risk of recurrence such that further treatment beyond excision (lumpectomy) is not required. In this issue, Wong et al report the results of a well-designed and well-conducted single-arm study in which the authors attempted to identify prospectively a cohort of DCIS patients with a sufficiently low risk of local recurrence after excision so that no additional treatment with radiation or tamoxifen was required. The importance of this study is that it is one of the first reported attempts to identify prospectively a low-risk subgroup of patients with DCIS who could be adequately treated with excision alone. The criteria for entry onto this study were based on commonly accepted clinical parameters for defining low-risk DCIS, including tumor size 2.5 cm, predominant nuclear grade 1 or 2, removal of all suspicious calcifications, and importantly, widely negative margins of resection (defined as a minimum negative margin width of 1 cm or a re-excision with no tumor). The reported annual risk of local recurrence was 2.4% per year, with an estimated 5-year local recurrence rate of 12%. This rate was higher than the predetermined acceptable rate of local recurrence, and therefore, the trial was closed to accrual early. It is noteworthy that the study by Wong et al failed to identify prospectively a low-risk cohort of patients suitable for treatment with excision alone. Given the small total number of patients in this study, many subsets contained too few patients for meaningful analysis. As a result, the study provides no substantive clues to improve patient selection in the future. In a similar prospective, single-arm trial of wide excision alone with a minimum negative margin width of 10 mm, Rampaul et al reported that the crude local recurrence rate was 11% (28 of 256 patients) after a median follow-up of 7.2 years. Attempts have been made at least as far back as the 1980s to identify a low-risk cohort of DCIS patients who do not require further treatment after excision. Numerous retrospective studies have analyzed selected patient populations to suggest criteria to define a low-risk subgroup, and many different criteria have been proposed. Most attempts have been based on clinical and pathologic criteria such as mammographic detection, small size (for example, 2.5 cm), widely clear margins of resection (for example, at least 1 cm in all directions), favorable pathologic features (for example, low or intermediate grade and absence of comedo necrosis), and patient age. Although promising, molecular and biologic markers (other than hormone receptors) currently do not influence management decisions. Retrospective studies are hypothesis generating, not hypothesis testing, and form the basis for prospective studies. In the setting of DCIS, the subgroup of patients for whom radiation can be omitted has not been prospectively and reproducibly identified in clinical trials. In retrospective studies of excision alone for selected patients with DCIS, 10-year local recurrence rates have been reported as 20% to 44%. An acceptable level of risk for local recurrence after treatment with excision alone has not been established and likely varies from patient to patient and from physician to physician. Three randomized trials of radiation for patients with DCIS have been reported to date. All three trials demonstrated that the risk of local recurrence, including invasive local recurrence, was reduced when definitive breast radiation was administered after excision compared with excision alone. Two of these trials used the straightforward random assignment of excision alone compared with excision plus radiation. In the National Surgical Adjuvant Breast and Bowel Project (NSABP) B17 trial, the 12-year risk of local recurrence was reduced with the addition of radiation from 31.7% to 15.7% (P .000005). The European Organization for JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L VOLUME 24 NUMBER 7 MARCH 1 2006