Meta-analysis of the impact of surgical margins on local recurrence in women with early-stage invasive breast cancer treated with breast-conserving therapy

Purpose: There is no consensus on what constitutes adequate negative margins in breast-conserving therapy (BCT). We review the evidence on surgical margins in BCT for early-stage invasive breast cancer.

Methods: Meta-analysis of studies reporting local recurrence (LR) relative to quantified final microscopic margin status and the threshold distance for negative margins. The proportion of LR was modelled using random effects logistic meta-regression.

Results: Based on 21 studies (LR in 1,026 of 14,571 subjects) the odds of LR were associated with margin status [model 1: odds ratio (OR) = 2.02 for positive/close versus negative; model 2: OR = 1.80 for close versus negative, 2.42 for positive versus negative (P<0.001 both models)] but not with margin distance [1mm versus 2mm versus 5mm (P > 0.10 both models)], adjusting for median follow-up time. However, there was weak evidence in both models that the odds of LR decreased as the threshold distance for declaring negative margins increased. This bordered significance in model 2 [OR for 1mm, 2mm, 5mm: 1.0, 0.75, 0.51 (P = 0.097 for trend)], and was not significant in model 1 [OR for 1mm, 2mm, 5mm: 1.0, 0.85, 0.58 (P = 0.11 for trend)] but was evident when one study (of women ≤ 40 years) was excluded from this model [OR for 1mm, 2mm, 5mm: 1.0, 0.72, 0.52 (P = 0.058 for trend)]: this trend was rendered insignificant by adjustment for the proportion of subjects receiving a radiation boost or the proportion of subjects receiving endocrine therapy.

Conclusions: Margin status has a prognostic effect in all women treated for invasive breast cancer; increasing the threshold distance for declaring negative margins is weakly associated with reduced odds of LR, however adjustment for covariates (adjuvant therapy) removes the significance of this effect. Adoption of wider margins, relative to narrower widths, for declaring negative margins is unlikely to a have substantial additional benefit for long-term local control in BCT.