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Originally published as JCO Early Release 10.1200/JCO.2007.13.9121 on November 5 2007 © 2007 American Society of Clinical Oncology.
Multifocal Ductal Carcinoma In Situ of the Breast: A Contraindication for Breast-Conserving Treatment?Department of Radiation Oncology, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, the Netherlands Multifocal ductal carcinoma in situ (DCIS) is usually considered a contraindication for breast-conserving treatment. Therefore, most patients will undergo mastectomy. In this issue of the Journal of Clinical Oncology, Rakovitch et al1 deserve credit for reporting the outcome of a large retrospective study of women with multifocal DCIS. Their patients were treated with breast-conserving treatment, with or without radiotherapy. The authors concluded that even for multifocal DCIS, breast-conserving treatment can lead to low recurrence rates, provided that the disease is completely excised and that radiation is administered. They are, therefore, adding another point for discussion, because the optimal treatment for DCIS—even for unifocal disease—is often debated and the role of radiotherapy questioned.2,3 Although DCIS is considered a precursor for invasive cancer, not all lesions will progress to invasive malignant disease. Long-term follow-up of women treated with biopsy alone showed that progression to invasive breast cancer was observed in 39% for patients with low-grade DCIS.4 It is also important to note that approximately 50% of the patients with local failure have an invasive local recurrence and, therefore, harbor the risk of developing distant metastasis. Identification of patients at high risk for local recurrence is critical for improvement of treatment in patients diagnosed with DCIS. Mastectomy is associated with the best control rates, but because of its mutilating effect is considered overtreatment for in situ disease. Breast-conserving treatment followed by radiotherapy of the breast has become an acceptable alternative for smaller lesions and provides survival rates comparable to those achieved with mastectomy.5 The earlier findings from the Ontario Breast Screening Program that concluded that women with multifocal DCIS were three times more likely to receive a mastectomy compared with those DCIS without urged Rakovitch et al to determine whether or not multifocality is an independent risk factor for local recurrence.6 A total number of 615 patients treated with breast-conserving treatment (305 with radiotherapy, 310 without radiotherapy) for DCIS were reviewed, including 260 patients (42%) with multifocal lesions. Because there are many definitions of multifocality, the authors used the definition from Sikand et al,7 who considered multifocality a pathologic feature defined as more than one distinct focus of DCIS, with at least 5 mm of intervening healthy breast tissue confined to a single quadrant of the breast. Although we know that complete excision is key to successful treatment, there is not yet uniform agreement on the minimal margin width necessary to ensure a safe treatment or to omit additional radiotherapy. Unfortunately, this study does not provide any new information on this matter. The reliability of histologic margin assessment is mainly influenced by the growth pattern of DCIS within the breast and by the distance between tumor foci. With the described detailed pathologic assessment in this study, the likelihood of a false free margin can be kept low and should encourage the use of conserving treatment for DCIS. Rakovitch et al found a detrimental effect of multifocality on the local recurrence rate only of those patients who did not receive radiotherapy, as reflected in a 10-year local recurrence–free rate of 59% for patients with multifocal DCIS compared with 80% for those without (P = .02). Radiotherapy after lumpectomy increased the local recurrence–free rate for multifocal DCIS, and no significant difference between multifocal and unifocal DCIS was observed (80% v87%, respectively; P = .35). Of note is the finding that there was no significant association between multifocality and the development of invasive breast cancer. Their observations favor the choice of breast-conserving treatment, including radiotherapy, for multifocal DCIS. In addition, Rakovitch et al properly observed that studies on multifocal DCIS conducted before the era of mammographic screening are not comparable to the contemporary population of patients. Therefore, multifocal disease should not be confused with extensive disease because the latter mandates treatment by mastectomy to ensure clear surgical margins. In the study by Rakovitch et al, the preoperative assessment was performed by mammography because this is still considered the most optimal method of detection. Although the findings have the limitation of a retrospective study, the study by Rakovitch et al suggests that, for patients with multifocal disease limited to one quadrant, breast-conserving treatment by complete wide local excision and radiotherapy is not contraindicated. Because a randomized clinical trial will probably be never performed to answer the issue on multifocality, the findings of this study should not be ignored. To further improve the results, magnetic resonance imaging (MRI) could be helpful to select multifocal lesions suitable for safe breast-conserving treatment and those that are not. Esserman et al8 reported earlier in the Journal about the value of MRI for imaging DCIS. Further, the complementary role of MRI to mammography has recently been reported in a large prospective observational study that showed that MRI improved the ability to detect particularly high-grade DCIS lesions.9 These new findings could aid the preoperative assessment and, in combination with a careful pathologic assessment, further potentiate the safety of breast-conserving treatment for DCIS. AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The author(s) indicated no potential conflicts of interest. AUTHOR CONTRIBUTIONS Conception and design: Philip Meijnen, Harry Bartelink Manuscript writing: Philip Meijnen, Harry Bartelink Final approval of manuscript: Philip Meijnen, Harry Bartelink REFERENCES
1. Rakovitch E, Pignol J-P, Hanna W, et al: Significance of multifocality in ductal carcinoma in situ: Outcomes of women treated with breast-conserving therapy. J Clin Oncol 25:5591-5596, 2007 2. Silverstein MJ, Lagios MD: Should all patients undergoing breast conserving therapy for DCIS receive radiation therapy? J Surg Oncol 95:605-609, 2007[CrossRef][Medline] 3. Buchholz TA, Haffty BG, Harris JR: Should all patients undergoing breast conserving therapy for DCIS receive radiation therapy? J Surg Oncol 95:610-613, 2007[CrossRef][Medline] 4. Sanders ME, Schuyler PA, Dupont WD, et al: The natural history of low-grade ductal carcinoma in situ of the breast in women treated by biopsy only revealed over 30 years of long-term follow-up. Cancer 103:2481-2484, 2005[CrossRef][Medline] 5. Bijker N, Meijnen P, Peterse JL, et al: Breast-conserving treatment with or without radiotherapy in ductal carcinoma-in-situ: Ten-year results of European Organisation for Research and Treatment of Cancer randomized phase III trial 10853—A study by the EORTC Breast Cancer Cooperative Group and EORTC Radiotherapy Group. J Clin Oncol 24:3381-3387, 2006 6. Rakovitch E, Pignol JP, Chartier C, et al: The management of ductal carcinoma in situ of the breast: A screened population-based analysis. Breast Cancer Res Treat 101:335-347, 2007[CrossRef][Medline] 7. Sikand K, Lee AH, Pinder SE, et al: Sections of the nipple and quadrants in mastectomy specimens for carcinoma are of limited value. J Clin Pathol 58:543-545, 2005 8. Esserman LJ, Kumar AS, Herrera AF, et al: Magnetic resonance imaging captures the biology of ductal carcinoma in situ. J Clin Oncol 24:4603-4610, 2006 9. Kuhl CK, Schrading S, Bieling HB, et al: MRI for diagnosis of pure ductal carcinoma in situ: A prospective observational study. Lancet 370:485-492, 2007[CrossRef][Medline] Related Article
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Copyright © 2007 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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