Table 1.

Summary of Clinical Practice Guideline Recommendations

Clinical Question	Recommendation	Strength of Recommendation	Level of Evidence	Strength of Evidence	Consensus on Recommendation
Are positive margins associated with an increased risk of IBTR? Can the use of WBRT mitigate this increased risk?	A positive margin, defined as ink on DCIS, is associated with a significant increase in IBTR; this increased risk is not nullified by the use of WBRT	Strong	Meta-analysis (patient level) of RCTs (not primary endpoint); meta-analysis (study level) of observational studies; individual RCT	Strong	100%
What margin width minimizes the risk of IBTR in patients receiving WBRT?	a. Margins of at least 2 mm are associated with a reduced risk of IBTR relative to narrower negative margin widths in patients receiving WBRT; b. the routine practice of obtaining negative margin widths wider than 2 mm is not supported by the evidence	a. Moderate b. Strong	Meta-analysis (study level) of observational studies	a. Moderate b. Strong	100%
Is treatment with excision alone and widely clear margins equivalent to treatment with excision and WBRT?	Treatment with excision alone, regardless of margin width, is associated with substantially higher rates of IBTR than treatment with excision and WBRT (even in pre-defined low-risk patients)	Strong	Meta-analysis (patient level) of RCTs; individual RCT	Strong	100%
What is the optimal margin width for patients treated with excision alone?	The optimal margin width for treatment with excision alone is unknown, but should be at least 2 mm. Some evidence suggests lower rates of IBTR with margin widths wider than 2 mm	Moderate	Meta-analysis observational studies; prospective single-arm studies; retrospective studies	Moderate	100%
What are the effects of endocrine therapy on IBTR? Is the benefit of endocrine therapy associated with negative margin width?	Rates of IBTR are reduced with endocrine therapy, but there is no evidence of an association between endocrine therapy and negative margin width.	Weak	RCTs	Weak	100%
Should margin widths greater than 2 mm be considered in the presence of unfavorable factors such as comedo necrosis, high grade, large size of DCIS, young patient age, negative ER status, or high risk multi-gene panel scores?	Multiple factors have been shown to be associated with the risk of IBTR in patients treated with and without WBRT, but there are no data addressing whether margin widths should be influenced by these factors	Weak	Expert opinion	Weak	100%
Should margin width be taken into consideration when determining WBRT delivery technique?	Choice of WBRT delivery technique, fractionation, and boost dose should not be dependent upon negative margin width. There is insufficient evidence to address optimal margin widths for APBI	Weak	Retrospective studies; expert opinion	Weak	100%
Should DCIS with microinvasion be considered as invasive carcinoma or DCIS when determining optimal margin width?	DCIS with microinvasion, defined as no invasive focus > 1 mm in size, should be considered as DCIS when considering the optimal margin width	Weak	Expert opinion	Weak	100%

IBTR, ipsilateral breast tumor recurrence; WBRT, whole breast radiation therapy; DCIS, ductal carcinoma in situ; RCT, randomized controlled trial; ER, estrogen receptor; APBI, accelerated partial breast irradiation