Monica Morrow, MD
Meena S. Moran, MD
A positive margin, defined as ink on ductal carcinoma in situ, is associated with a significant increase in ipsilateral breast tumor recurrence; this increased risk is not nullified by the use of whole-breast irradiation.— Monica Morrow, MD, Meena S. Moran, MD, and colleagues
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A clinical practice guideline on margins for breast-conserving surgery with whole-breast irradiation in ductal carcinoma in situ has been jointly developed by the Society of Surgical Oncology (SSO), the American Society for Radiation Oncology (ASTRO), and ASCO.1-3 The recommendations were developed by a multidisciplinary expert panel using the best available evidence on the topic and expert consensus opinion. A meta-analysis of margin width and ipsilateral breast tumor recurrence from a systematic review of 20 studies including 7,883 patients and other literature sources served as the evidence base for the guideline. The panel was co-chaired by Monica Morrow, MD, of Memorial Sloan Kettering Cancer Center, New York, and Meena S. Moran, MD, of Yale University, New Haven, Connecticut, and the guideline is jointly published by Dr. Morrow and colleagues in the Journal of Clinical Oncology,1 Annals of Surgical Oncology,2 and Practical Radiation Oncology.3
The key clinical questions and recommendations are summarized/reproduced here, with the strength of recommendation, level of evidence, and strength of evidence shown in brackets. The level of consensus was 100% for all recommendations.
Key Recommendations
Are positive margins associated with an increased risk of ipsilateral breast tumor recurrence? Can the use of whole-breast irradiation mitigate this increased risk?
Recommendation: A positive margin, defined as ink on ductal carcinoma in situ, is associated with a significant increase in ipsilateral breast tumor recurrence; this increased risk is not nullified by the use of whole-breast irradiation. [Recommendation strength = strong; Level of evidence = meta-analysis (patient level) of randomized controlled trials (not primary endpoint), meta-analysis (study level) of observational studies, individual randomized controlled trials; Evidence strength = strong]
What margin width minimizes the risk of ipsilateral breast tumor recurrence in patients receiving whole-breast irradiation?
Recommendation: (a) Margins of at least 2 mm are associated with a reduced risk of ipsilateral breast tumor recurrence relative to narrower negative margin widths in patients receiving whole-breast irradiation. (b) The routine practice of obtaining negative margin widths wider than 2 mm is not supported by the evidence. [Recommendation strength: a = moderate, b = strong; Level of evidence = meta-analysis (study level) of observational studies; Evidence strength: a = moderate, b = strong]
Is treatment with excision alone and widely clear margins equivalent to treatment with excision and whole-breast irradiation?
Recommendation: Treatment with excision alone, regardless of the margin width, is associated with substantially higher rates of ipsilateral breast tumor recurrence than treatment with excision and whole-breast irradiation (even in predefined low-risk patients). [Recommendation strength = strong; Level of evidence = meta-analysis (patient level) of randomized controlled trials, individual randomized controlled trials; Evidence strength = strong]
What is the optimal margin width for patients treated with excision alone?
Recommendation: The optimal margin width for treatment with excision alone is unknown, but it should be at least 2 mm. Some evidence suggests lower rates of ipsilateral breast tumor recurrence with margin widths wider than 2 mm. [Recommendation strength = moderate; Level of evidence = meta-analysis (study level) of observational studies, prospective single-arm studies, retrospective studies; Evidence strength = moderate]
What are the effects of endocrine therapy on ipsilateral breast tumor recurrence? Is the benefit of endocrine therapy associated with negative margin width?
Recommendation: Rates of ipsilateral breast tumor recurrence are reduced with endocrine therapy, but there is no evidence of an association between endocrine therapy and negative margin width. [Recommendation strength = weak; Level of evidence = randomized controlled trials; Evidence strength = weak]
Should margin widths greater than 2 mm be considered in the presence of unfavorable factors such as comedo necrosis, high grade, large size of ductal carcinoma in situ, young patient age, negative estrogen receptor status, or high-risk multigene panel scores?
Recommendation: Multiple factors have been shown to be associated with the risk of ipsilateral breast tumor recurrence in patients treated with and without whole-breast irradiation, but there are no data addressing whether margin widths should be influenced by these factors. [Recommendation strength = weak; Level of evidence = expert opinion; Evidence strength = weak]
Should margin width be taken into consideration when determining the delivery technique of whole-breast irradiation?
Recommendation: Choice of the delivery technique, fractionation, and boost dose for whole-breast irradiation should not be dependent upon negative margin width. There is insufficient evidence to address optimal margin widths for accelerated partial-breast irradiation. [Recommendation strength = weak; Level of evidence = retrospective studies, expert opinion; Evidence strength = weak]
Should ductal carcinoma in situ with microinvasion be considered as invasive carcinoma or ductal carcinoma in situ when determining optimal margin width?
Recommendation: Ductal carcinoma in situ with microinvasion, defined as no invasive focus > 1 mm, should be considered as ductal carcinoma in situ when determining the optimal margin width. [Recommendation strength = weak; Level of evidence = expert opinion; Evidence strength = weak]. ■
Disclosure: Drs. Morrow and Moran reported no potential conflicts of interest.
References
2. Morrow M, Van Zee KJ, Solin LJ, et al: Society of Surgical Oncology-American Society for Radiation Oncology-American Society of Clinical Oncology consensus guideline on margins for breast-conserving surgery with whole-breast irradiation in ductal carcinoma in situ. Ann Surg Oncol 23:3801-3810, 2016.
3. Morrow M, Van Zee KJ, Solin LJ, et al: Society of Surgical Oncology-American Society for Radiation Oncology-American Society of Clinical Oncology consensus guideline on margins for breast-conserving surgery with whole-breast irradiation in ductal carcinoma in situ. Pract Radiat Oncol 6:287-295, 2016.
