medwireNews: Involved or close pathologic margins after breast conserving surgery are associated with an increased risk for distant recurrence and mortality in women with early-stage invasive breast cancer, indicates a meta-analysis.
“A margin of no tumour on ink is inadequate and we recommend a minimum tumour free distance of 1 mm from the margin for either invasive disease or ductal carcinoma in situ to ensure optimum oncological outcomes,” say Nigel Bundred (University of Manchester, UK) and co-authors in The BMJ.
They suggest: “If, as is likely, the association between margin involvement and higher distant recurrence and mortality is causal, a reappraisal of existing international guidelines is needed.”
Bundred and colleagues explain that previous research has demonstrated that involved or close margins “are associated with an increased risk of local recurrence,” but “[t]he effect of margin involvement on distant recurrence or mortality is relatively unknown.”
They therefore conducted a meta-analysis of 68 studies comprising 112,140 patients who underwent breast conserving surgery for stage I–III disease. Of these patients, 9.4% had involved margins (defined as tumor on ink) and 17.8% had close margins (no tumor on ink but <2 mm), and the remainder had negative margins, of at least 2 mm.
The rate of distant recurrence was highest among patients with involved margins, at 25.4%, followed by rates of 8.4% and 7.4% among those with close and negative margins, respectively. The corresponding rates of local recurrence were 15.9%, 8.8%, and 3.9%.
Pooled analysis of five studies showed that involved margins were associated with a significantly increased risk for distant recurrence relative to negative margins, with a multivariate hazard ratio (HR) of 2.10.
The risk for distant recurrence was also significantly higher for close versus negative margins, at an HR of 1.38 in a pooled analysis of three studies.
Compared with negative margins, involved margins were also significantly associated with an elevated risk for local recurrence, at an HR of 1.98 in 12 studies, and this was also the case for close margins, at an HR of 2.09 in six studies.
Analysis of the two studies reporting on overall survival showed a significant association between involved margins and an increased mortality risk versus negative margins (HR=1.61), while involved or close margins were associated with a numerically elevated risk (HR=1.32).
The study authors note that this is “the largest meta-analysis of the association between margins after breast conserving surgery and outcomes.”
And they conclude: “Our study shows that margin proximity is associated with increased distant recurrence (as well as local recurrence), so the chosen margin width is important and should minimise distant recurrence.
“Some distant recurrences probably result from involved margins, and in the future, multidisciplinary team decisions about margin clearance width should ensure maximal prevention of distant recurrence.”
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