European Journal of Cancer
Volume 46, Issue 18 , Pages 3219-3232, December 2010

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

  • Nehmat Houssami

      Affiliations

    • Screening and Test Evaluation Program (STEP), School of Public Health, Sydney Medical School, University of Sydney, Sydney, Australia
    • Corresponding Author InformationCorresponding author: Address: School of Public Health (A27), Sydney Medical School, University of Sydney, Sydney 2006, Australia. Tel.: +61 (0) 419 273510; fax +61 (0) 2 9705 1046.
    • ,
  • Petra Macaskill

      Affiliations

    • Screening and Test Evaluation Program (STEP), School of Public Health, Sydney Medical School, University of Sydney, Sydney, Australia
    • ,
  • M. Luke Marinovich

      Affiliations

    • Screening and Test Evaluation Program (STEP), School of Public Health, Sydney Medical School, University of Sydney, Sydney, Australia
    • ,
  • J. Michael Dixon

      Affiliations

    • Breakthrough Research Unit Edinburgh, Western General Hospital, Edinburgh, Scotland, United Kingdom
    • ,
  • Les Irwig

      Affiliations

    • Screening and Test Evaluation Program (STEP), School of Public Health, Sydney Medical School, University of Sydney, Sydney, Australia
    • ,
  • Meagan E. Brennan

      Affiliations

    • Screening and Test Evaluation Program (STEP), School of Public Health, Sydney Medical School, University of Sydney, Sydney, Australia
    • ,
  • Lawrence J. Solin

      Affiliations

    • Department of Radiation Oncology, Albert Einstein Medical Center, Philadelphia, PA, USA

Received 8 July 2010; received in revised form 26 July 2010; accepted 28 July 2010. published online 03 September 2010.

Abstract 

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⩽40years) 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.

Keywords: Invasive breast cancer, Breast-conserving therapy, Surgical margins, Local recurrence, Radiation therapy, Surgical oncology, Meta-analysis

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☆ This work was partly funded by the National Health and Medical Research Council (NHMRC) program grant 402764 to the Screening & Test Evaluation Program.

PII: S0959-8049(10)00753-7

doi:10.1016/j.ejca.2010.07.043

European Journal of Cancer
Volume 46, Issue 18 , Pages 3219-3232, December 2010

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