Clinical Investigation
Society of Surgical Oncology–American Society for Radiation Oncology Consensus Guideline on Margins for Breast-Conserving Surgery With Whole-Breast Irradiation in Stages I and II Invasive Breast Cancer

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Purpose

To convene a multidisciplinary panel of breast experts to examine the relationship between margin width and ipsilateral breast tumor recurrence (IBTR) and develop a guideline for defining adequate margins in the setting of breast conserving surgery and adjuvant radiation therapy.

Methods and Materials

A multidisciplinary consensus panel used a meta-analysis of margin width and IBTR from a systematic review of 33 studies including 28,162 patients as the primary evidence base for consensus.

Results

Positive margins (ink on invasive carcinoma or ductal carcinoma in situ) are associated with a 2-fold increase in the risk of IBTR compared with negative margins. This increased risk is not mitigated by favorable biology, endocrine therapy, or a radiation boost. More widely clear margins than no ink on tumor do not significantly decrease the rate of IBTR compared with no ink on tumor. There is no evidence that more widely clear margins reduce IBTR for young patients or for those with unfavorable biology, lobular cancers, or cancers with an extensive intraductal component.

Conclusions

The use of no ink on tumor as the standard for an adequate margin in invasive cancer in the era of multidisciplinary therapy is associated with low rates of IBTR and has the potential to decrease re-excision rates, improve cosmetic outcomes, and decrease health care costs.

Introduction

Multiple randomized, phase III trials with mature follow-up have conclusively demonstrated that survival after breast-conserving therapy (BCT), defined as surgical excision of the primary tumor and a margin of surrounding normal tissue followed by whole-breast radiation therapy (WBRT), is equivalent to mastectomy for the treatment of stages I and II invasive breast cancer (BC) 1, 2. Of these trials, only one, the National Surgical Adjuvant Breast and Bowel Project (NSABP) B06, required a microscopically clear margin, defined as no ink on tumor (2); all others required complete gross removal of the tumor but did not specify a microscopic margin width. Although BCT has been standard practice for more than 20 years, there is still no consensus on what constitutes an optimal negative margin width 3, 4 As a consequence, approximately 1 in 4 women attempting BCT undergo a re-excision, and nearly half of these procedures are performed with the rationale of obtaining more widely clear margins in women whose margins are negative, as defined by no ink on tumor 5, 6. These additional surgical procedures have the potential for added discomfort, surgical complications, compromise in cosmetic outcome, unnecessary additional emotional stress for patients and families, and increased health care costs, and have been associated with patient preference for conversion to bilateral mastectomy (7). In the past 30 years since the randomized trials that established the equivalence of BCT and mastectomy, the landscape of BC management has changed dramatically. Breast imaging has improved, and adjuvant systemic therapy is now commonly used, even for small, node-negative BCs, resulting in a decline in rates of ipsilateral breast tumor recurrence (IBTR) (8).

In view of these changes, the Society of Surgical Oncology (SSO) and American Society for Radiation Oncology (ASTRO) convened a multidisciplinary expert panel (ie, Margins Panel [MP]) in 2013 for the purpose of examining the relationship between margin width and IBTR. The primary clinical question was: What margin width minimizes the risk of IBTR? Specific clinical circumstances that might have an impact on this question, such as tumor histology, patient age, use of systemic therapy, and technique of radiation delivery, were also examined. The guideline developed from this consensus panel is intended to assist treating physicians and patients in the clinical decision-making process. As with any guideline, the monitoring of outcomes at the institutional level is encouraged. The key findings of the guideline are summarized in Table 1.

Section snippets

Methods and Materials

The Margins Panel (MP) comprised a multidisciplinary group of experts designated by their respective organizations, an expert methodologist who led the evidence review, and a patient representative (Table 2). The process for development of this guideline followed, to the extent possible, the standards of the Institute of Medicine (IOM) (9). The panel commissioned a systematic review and meta-analysis of the literature as the primary evidence base for the guideline. Additional literature reviews

Results

The margins meta-analysis was based on 33 eligible studies published between 1965 and 2013. The analysis included 28,162 patients, of whom 1506 had an IBTR. The median follow-up was 79.2 months, and the median prevalence of IBTR was 5.3% (interquartile range, 2.3-7.6%). Patients with unknown margin status were not included in the analysis. Table 3 summarizes the characteristics of the studies, and the patient, tumor, and treatment variables included in this analysis. Houssami et al (13) provide

Acknowledgments

The authors thank David Euhus, MD (Society of Surgical Oncology [SSO]), Beryl McCormick, MD (American Society for Radiation Oncology [ASTRO]), Benjamin Smith, MD (ASTRO), Kimberly Van Zee, MD (SSO), and Lee Wilkie, MD (SSO) for critical review of the manuscript, and Shan-san Wu for editorial assistance.

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