Meta-analysis of the impact of surgical margins on local recurrence in women with early-stage invasive breast cancer treated with breast-conserving therapy |
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| Authors: | Nehmat Houssami Petra Macaskill M. Luke Marinovich J. Michael Dixon Les Irwig Meagan E. Brennan Lawrence J. Solin |
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| Affiliation: | 1. Screening and Test Evaluation Program (STEP), School of Public Health, Sydney Medical School, University of Sydney, Sydney, Australia;2. Breakthrough Research Unit Edinburgh, Western General Hospital, Edinburgh, Scotland, United Kingdom;3. Department of Radiation Oncology, Albert Einstein Medical Center, Philadelphia, PA, USA;1. NRG Oncology, Pittsburgh, PA, USA;2. MHP Radiation Oncology Institute, St Joseph Mercy Hospital Campus, Pontiac, MI, USA;3. University of Pittsburgh, Pittsburgh, PA, USA;4. Ohio State University Comprehensive Cancer Center—Arthur G James Cancer Hospital and Richard J Solove Research Institute, Columbus, OH, USA;5. Massey Cancer Center, Virginia Commonwealth University, Richmond, VA, USA;6. Allegheny Health Network Cancer Institute, Pittsburgh, PA, USA;7. University of Colorado Cancer Center, Aurora, CO, USA;8. Arizona Breast Cancer Specialists, Arizona Center for Cancer Care, Scottsdale, AZ, USA;9. University of California at Los Angeles, Los Angeles, CA, USA;10. Carnegie Mellon University, Pittsburgh, PA, USA;11. NRG Oncology Statistics and Data Management Center, American College of Radiology, Philadelphia, PA, USA;12. Yonsei University College of Medicine, Seoul, Korea;13. MD Anderson Cancer Center, Houston, TX, USA;14. Mayo Clinic Florida, Jacksonville, FL, USA;15. Southwest Oncology Group Cancer Research Network, Hope Foundation for Cancer Research, Portland, OR, USA;p. Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA;q. Orlando Health, UF Health Cancer Center, Orlando, FL, USA;r. Memorial Sloan Kettering Cancer Center, New York, NY, USA;s. Centre Hospitalier Universitaire de Québec—Université Laval, Pavillon Hôtel-Dieu de Québec, Québec City, QC, Canada;t. Community Clinical Oncology Program, William Beaumont Hospital, Sterling Heights, MI, USA;u. Summit Cancer Center, Post Falls, ID, USA;v. Mayo Clinic, Rochester, MN, USA;w. Saint Agnes Hospital, Baltimore, MD, USA;x. Thomas Jefferson University, Baltimore, MD, USA;y. Winship Cancer Institute of Emory University, Atlanta, GA, USA;1. Division of Reconstructive Surgery, European Institute of Oncology, Via Ripamonti 435, Milan, Italy;2. Division of Epidemiology and Biostatistics, European Institute of Oncology, Milan, Italy;3. Department of Statistics and Quantitative Methods, University of Milan-Bicocca, Milan, Italy;4. Division of Anesthesia, European Institute of Oncology, Milan, Italy;5. Division of Radiotherapy, European Institute of Oncology, Milan, Italy;6. University of Milan, Milan, Italy;7. Division of Surgical Senology, European Institute of Oncology, Milan, Italy;1. Lewisham and Greenwich NHS Trust, London, UK;2. Homerton University Hospital Foundation Trust, London, UK;3. The London Breast Institute, The Princess Grace Hospital, London, UK;4. King’s College Hospital NHS Foundation Trust, London, UK;1. Endoscopic & Oncoplastic Breast Surgery Center, Changhua Christian Hospital, Changhua, Taiwan;2. Comprehensive Breast Cancer Center, Changhua Christian Hospital, Changhua, Taiwan;3. Division of General Surgery, Department of Surgery, Changhua Christian Hospital, Changhua, Taiwan;4. School of Medicine, National Yang Ming University, Taipei, Taiwan;5. Department of Surgical Pathology, Changhua Christian Hospital, Taiwan;6. School of Medicine, Chung Shan Medical University, Taichung, Taiwan;7. Tumor Center, Changhua Christian Hospital, Changhua, Taiwan;8. Department of Radiology, Changhua Christian Hospital, Taiwan;9. Breast Surgery Center, Division of General Surgery, Department of Surgery, Cardinal Tien Hospital, Taipei, Taiwan;10. Department of Surgery, Wuri Lin Shin Hospital, Taichung, Taiwan;11. Kaohsiung Medical University, Kaohsiung, Taiwan |
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| Abstract: | ![]()
PurposeThere 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.MethodsMeta-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.ResultsBased 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 [1 mm versus 2 mm versus 5 mm (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 1 mm, 2 mm, 5 mm: 1.0, 0.75, 0.51 (P = 0.097 for trend)], and was not significant in model 1 [OR for 1 mm, 2 mm, 5 mm: 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 1 mm, 2 mm, 5 mm: 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.ConclusionsMargin 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. |
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