Significance of Multifocality in Ductal Carcinoma In Situ: Outcomes of Women Treated With Breast- Conserving Therapy Eileen Rakovitch, Jean-Philippe Pignol, Wedad Hanna, Steven Narod, Jacqueline Spayne, Sharon Nofech-Mozes, Carole Chartier, and Lawrence Paszat A B S T R A C T Purpose There is concern that women with multifocal ductal carcinoma in situ (DCIS; confined to one quadrant) who are treated with breast-conserving surgery face a high risk of local recurrence; therefore, many are treated with mastectomy. The objective of this study is to evaluate the significance of multifocality and the outcomes of women with multifocal DCIS treated with breast-conserving therapy. Methods The records of patients treated with breast-conserving surgery for DCIS between 1982 and 2000 were reviewed. Multivariate analyses were performed to evaluate the effects of multifocality and other prognostic factors on the rate of local recurrence. Results Of 615 cases of DCIS reviewed, 310 (41%) received breast-conserving surgery and 305 (40%) received breast-conserving surgery plus radiation (n = 260 with multifocality, n = 314 without multifocality, and n = 31 focality unreported). On multivariate analysis, multifocality (hazard ratio [HR] = 1.80; 95% CI, 1.15 to 2.80; P = .01), radiation treatment (HR = 0.46; 95% CI, 0.29 to 0.74; P = .001), margin width 4 mm or smaller (HR = 1.74; 95% CI, 1.03 to 2.92; P = .04), and high nuclear grade (HR = 1.65; 95% CI, 1.02 to 2.65; P = .04) were associated with risk of local recurrence. The detrimental effect of multifocality was limited to women who did not receive radiotherapy; the local recurrence–free survival rate at 10 years was 59% for women with multifocal disease and 80% for women without multifocality (P = .02). Among women treated with breast-conserving surgery plus radiation, there was no difference in 10-year local recurrence– free survival (80% v 87%; P = .35). There was no association between multifocality and the development of invasive recurrence. Conclusion Multifocality is a significant predictor of local recurrence in women who receive breast-conserving surgery for DCIS without radiotherapy; however, low recurrence rates can be achieved if adjuvant radiation is administered. J Clin Oncol 25:5591-5596. © 2007 by American Society of Clinical Oncology INTRODUCTION Ductal carcinoma in situ (DCIS) is a noninvasive form of breast cancer and is defined by the presence of malignant epithelial cells confined to the breast ductule. 1 The increased utilization of screening mammography during the last 20 years has lead to a dramatic rise in the incidence of DCIS, and now DCIS represents 20% to 40% of all breast cancers diagnosed by screening mammography. 2 The prog- nosis of DCIS is excellent, with 10-year survival rates in excess of 95%. 3-5 The goal of treatment is to excise the entire lesion, leaving negative resection margins, to minimize the risk of further recurrence (in situ or invasive) and to avoid further surgery, hormone therapy, and chemotherapy (in the event of an inva- sive recurrence). Before the era of mammographic screening, the treatment of DCIS was largely by mastectomy, because DCIS was usually extensive at diagnosis, often involving most of the breast. 1 The advent of screening mammography has led to a significant decrease in the median size of DCIS lesions at pre- sentation. 6 Today, most cases of DCIS can be treated with breast-conserving surgery, providing a good cosmetic outcome. Nevertheless, approximately one From the Departments of Radiation Oncology and Pathology, Toronto- Sunnybrook Odette Cancer Centre, Sunnybrook Health Sciences Centre; and the Centre for Research in Women’s Health, Women’s College Hospital, University of Toronto, Toronto, Ontario, Canada. Submitted March 6, 2007; accepted August 7, 2007; published online ahead of print at www.jco.org on November 5, 2007. Authors’ disclosures of potential con- flicts of interest and author contribu- tions are found at the end of this article. Address reprint requests to Eileen Rakovitch, MD, MSc, FRCPC, Toronto- Sunnybrook Odette Cancer Centre, Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Toronto, Ontario, Canada M4N 3M5; e-mail: eileen.rakovitch@sunnybrook.ca. © 2007 by American Society of Clinical Oncology 0732-183X/07/2535-5591/$20.00 DOI: 10.1200/JCO.2007.11.4686 JOURNAL OF CLINICAL ONCOLOGY O R I G I N A L R E P O R T VOLUME 25  NUMBER 35  DECEMBER 10 2007 5591