International Journal of Radiation Oncology*Biology*Physics
Clinical InvestigationSociety 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
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.
References (72)
- et al.
Preferred reporting items for systematic reviews and meta-snalyses: The PRISMA statement
J Clin Epidemiol
(2009) - et al.
Meta-analysis of the impact of surgical margins on local recurrence in women with early-stage invasive breast cancer treated with breast-conserving therapy
Eur J Cancer
(2010) - et al.
Factors determining outcome for breast-conserving irradiation with margin-directed dose escalation to the tumor bed
Int J Radiat Oncol Biol Phys
(1998) - et al.
Local relapse rates are falling after breast conserving surgery and systemic therapy for early breast cancer: Can radiotherapy ever be safely withheld?
Radiother Oncol
(2009) - et al.
The pancake phenomenon contributes to the inaccuracy of margin assessment in patients with breast cancer
Am J Surg
(2002) Margins of “lumpectomy” for breast cancer
Hum Pathol
(1986)- et al.
2-Year follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer: A randomised controlled trial
Lancet
(2007) - et al.
Outcome in breast molecular subtypes according to nodal status and surgical procedures
Am J Surg
(2013) - et al.
Randomised trial of standard 2D radiotherapy (RT) versus intensity modulated radiotherapy (IMRT) in patients prescribed breast radiotherapy
Radiother Oncol
(2007) - et al.
Radiotherapy boost dose-escalation for invasive breast cancer after breast-conserving surgery: 2093 Patients treated with a prospective margin-directed policy
Radiother Oncol
(2013)
Impact of the radiation boost on outcomes after breast-conserving surgery and radiation
Int J Radiat Oncol Biol Phys
Clinical-pathologic features, long term-outcome and surgical treatment in a large series of patients with invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC)
Eur J Surg Oncol
A comparative analysis of lobular and ductal carcinoma of the breast: Presentation, treatment, and outcomes
J Am Coll Surg
Lobular carcinoma in situ as a component of breast cancer: The long-term outcome in patients treated with breast-conservation therapy
Int J Radiat Oncol Biol Phys
Isolated loco-regional recurrence of breast cancer is more common in young patients and following breast conserving therapy: Long-term results of European Organisation for Research and Treatment of Cancer studies
Eur J Cancer
Prognosis and adjuvant treatment effects in selected breast cancer subtypes of very young women (<35 years) with operable breast cancer
Ann Oncol
Breast conservation therapy: The influence of molecular subtype and margins
Int J Radiat Oncol Biol Phys
Effect of radiotherapy after breast-conserving surgery on 10-year recurrence and 15-year breast cancer death: Meta-analysis of individual patient data for 10,801 women in 17 randomised trials
Lancet
Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer
N Engl J Med
What is an adequate margin for breast-conserving surgery? Surgeon attitudes and correlates
Ann Surg Oncol
Current perceptions regarding surgical margin status after breast-conserving therapy: Results of a survey
Ann Surg
Variability in reexcision following breast conservation surgery
JAMA
Surgeon recommendations and receipt of mastectomy for treatment of breast cancer
JAMA
Clinical management factors contribute to the decision for contralateral prophylactic mastectomy
J Clin Oncol
Prognosis after ipsilateral breast tumor recurrence and locoregional recurrences in patients treated by breast-conserving therapy in five National Surgical Adjuvant Breast and Bowel Project protocols of node-negative breast cancer
J Clin Oncol
Multicenter surveillance of women at high genetic breast cancer risk using mammography, ultrasonography, and contrast-enhanced magnetic resonance imaging (the High Breast Cancer Risk Italian 1 Study): Final results
Invest Radiol
Sequencing of chemotherapy and radiation therapy in early-stage breast cancer: Updated results of a prospective randomized trial
J Clin Oncol
Differences in risk factors for local and distant recurrence after breast-conserving therapy or mastectomy for stage I and II breast cancer: Pooled results of two large European randomized trials
J Clin Oncol
Ten-year results in 1070 patients with stages I and II breast cancer treated by conservative surgery and radiation therapy
Cancer
Impact of a higher radiation dose on local control and survival in breast-conserving therapy of early breast cancer: 10-Year results of the randomized boost versus no boost EORTC 22881-10882 trial
J Clin Oncol
Impact of pathological characteristics on local relapse after breast-conserving therapy: A subgroup analysis of the EORTC boost versus no boost trial
J Clin Oncol
Histologic multifocality of Tis, T1-2 breast carcinomas: Implications for clinical trials of breast-conserving surgery
Cancer
The relationship between shaved margin and inked margin status in breast excision specimens
Cancer
Treatment of axillary lymph node-negative, estrogen receptor-negative breast cancer: Updated findings from National Surgical Adjuvant Breast and Bowel Project clinical trials
J Natl Cancer Inst
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Supported by a grant from Susan G. Komen.