The association of surgical margins and local recurrence in women with early-stage invasive breast cancer treated with breast-conserving therapy: a meta-analysis

Abstract

Purpose: There is no consensus on what constitutes adequate negative margins in breast-conserving therapy (BCT). We systematically review the evidence on surgical margins in BCT for invasive breast cancer to support the development of clinical guidelines.

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

Results: Based on 33 studies (LR in 1,506 of 28,162), the odds of LR were associated with margin status [model 1: odds ratio (OR) 1.96 for positive/close vs negative; model 2: OR 1.74 for close vs. negative, 2.44 for positive vs. negative; (P < 0.001 both models)] but not with margin distance [model 1: >0 mm vs. 1 mm (referent) vs. 2 mm vs. 5 mm (P = 0.12); and model 2: 1 mm (referent) vs. 2 mm vs. 5 mm (P = 0.90)], adjusting for study median follow-up time. There was little to no statistical evidence that the odds of LR decreased as the distance for declaring negative margins increased, adjusting for follow-up time [model 1: 1 mm (OR 1.0, referent), 2 mm (OR 0.95), 5 mm (OR 0.65), P = 0.21 for trend; and model 2: 1 mm (OR 1.0, referent), 2 mm (OR 0.91), 5 mm (OR 0.77), P = 0.58 for trend]. Adjustment for covariates, such as use of endocrine therapy or median-year of recruitment, did not change the findings.

Conclusions: Meta-analysis confirms that negative margins reduce the odds of LR; however, increasing the distance for defining negative margins is not significantly associated with reduced odds of LR, allowing for follow-up time. Adoption of wider relative to narrower margin widths to declare negative margins is unlikely to have a substantial additional benefit for long-term local control in BCT.

Figure 1

The effect of margin status (positive/close relative to negative) on local recurrence: Study-specific odds ratios, ordered by median follow-up time. Figure shows a crude pooled odds ratio of 1.97 (CI 1.73 – 2.25) [modeled pooled odds ratio, adjusted for negative distance was 1.98 (CI 1.73 – 2.25) and also adjusted for median follow-up time was 1.96 (CI 1.72 – 2.24)]. Data for Mirza and Ewertz are for loco-regional recurrence.

Figure 2

Study-specific proportion with local recurrence (LR) stratified by threshold distance for negative margins, ordered by median follow-up time. Data for Neuschatz were based on a 5mm distance; data for Perez were based on a 3mm distance (this was included in the 5mm group in our analysis); data for Mirza and Ewertz were for loco-regional recurrence.