Although breast-conserving therapy has been a standard practice for more than 20 years, controversy still exists over what constitutes the appropriate margin of normal breast tissue around a tumor that minimizes local recurrence while maintaining a good cosmetic outcome. Surveys of surgeons1 and radiation oncologists2 failed to identify a margin width that more than 50% of respondents endorsed as adequate. As a consequence, reexcision to obtain more widely clear margins is a frequent procedure, performed in 19% of stage I and stage II breast cancer patients in a population-based sample reported by Morrow et al3 and 23% of a large convenience sample reported by McCahill et al.4 In the study by McCahill et al, 48% of the reexcisions were performed for margins that were negative, defined as “no ink on tumor cells” (ie, no cancerous cells touching the edge of the lumpectomy specimen).
Lack of Data
The margin question has never been directly addressed in a prospective randomized trial. The National Surgical Adjuvant Breast and Bowel Project (NSABP) B-06 trial used a margin definition of no ink on tumor cells5 and found no statistically significant differences in survival or local recurrence between patients treated with breast-conserving therapy and those treated with mastectomy. The NSABP B-06 trial was the only one of the randomized trials comparing breast-conserving therapy and mastectomy to employ a microscopic margin definition; in spite of this, over time, bigger margins came to be perceived as better margins, leading to the current state of confusion.
Breast cancer care has changed dramatically in the 30 years since the initial trials of breast-conserving therapy. Mammography is greatly improved, pathologic examination of lumpectomy specimens is more detailed, and the majority of patients with invasive breast cancer receive systemic therapy. These factors, coupled with the frequent use of reexcision, led the Society of Surgical Oncology (SSO) and the American Society for Radiation Oncology (ASTRO) to convene a consensus panel to address the question of the optimal margin width in breast-conserving therapy. The resultant guideline was published in Annals of Surgical Oncology, International Journal of Radiation Oncology Biology Physics, and Journal of Clinical Oncology6 and is summarized in this issue of The ASCO Post.
A systematic review and meta-analysis of the literature7 was the primary evidence base for the consensus. In evaluating the results of the meta-analysis, the consensus group gave strong weight to three factors: (1) a negative margin does not indicate the absence of residual tumor in the breast8; (2) measurement of margin width is an inexact science9; and (3) rates of local recurrence vary with tumor biology and are decreased with systemic therapy.10
Study Specifics
The margins meta-analysis included 26,162 patients in 33 studies published between 1965 and 2013.7 In spite of the fact that only 40% of included patients received any systemic therapy, the median crude rate of local recurrence was only 5.3% (95% confidence interval = 2.3%–7.6%). No statistically significant differences in local recurrence were seen when margins of 1 mm, 2 mm, and 5 mm were compared using statistical tests for association and trend. Adjustment of the model for covariates of patient age, median year of study recruitment, estrogen receptor status, use of endocrine therapy, and reexcision did not change these results.
The meta-analysis was unable to directly compare margins of no ink on tumor to 1-mm margins due to both the small number of studies employing this margin definition and the statistical methodology used. However, the panel felt that the large experience of the NSABP using the margin definition of no ink on tumor with low rates of local recurrence,11 coupled with the lack of standardization of margin assessment, indicated that margins of ink not touching tumor and 1 mm were unlikely to be meaningfully different.
Practical Implications
The practical implications of the consensus statement are substantial. Rules that many practices and tumor boards have put into place stating that all margins must be 1 mm, 5 mm, 1 cm, or some other arbitrary width are not supported by the evidence and should be abandoned.
The consensus guideline does not imply that there are no indications for margins more widely clear than no ink on tumor. Patients at risk for a high residual disease burden, who can be recognized by large amounts of tumor in proximity to the margin, particularly when coupled with the discontinuous growth pattern seen with infiltrating lobular carcinoma or an extensive intraductal component in association with invasive cancer, should continue to undergo reexcision. However, the need for reexcision should be determined on a case-by-case basis.
This margin guideline acknowledges the reality of breast cancer treatment in the current era and uses these advances to decrease the burden of treatment for patients. This approach will also decrease health-care costs. The consensus panel members hope it will be widely adopted by the breast cancer community. ■
Disclosure: Dr. Morrow is Co-Chair of the SSO-ASTRO Margin Panel.
Dr. Morrow is Chief of the Breast Service and Anne Burnett Windfohr Chair of Clinical Oncology at Memorial Sloan Kettering Cancer Center, and Professor of Surgery at Weill Cornell Medical College, New York. She is also Co-Chair of the SSO-ASTRO Margin Panel.
References
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2. Taghian A, Mohiuddin M, Jagsi R, et al: Current perceptions regarding surgical margin status after breast-conserving therapy: Results of a survey. Ann Surg 241:629-639, 2005.
3. Morrow M, Jagsi R, Alderman AK, et al: Surgeon recommendations and receipt of mastectomy for treatment of breast cancer. JAMA 302:1551-1556, 2009.
4. McCahill LE, Single RM, Aiello Bowles EJ, et al: Variability in reexcision following breast conservation surgery. JAMA 307:467-475, 2012.
5. Fisher B, Redmond C, Poisson R, et al: Eight-year results of a randomized clinical trial comparing total mastectomy and lumpectomy with or without irradiation in the treatment of breast cancer. N Engl J Med 320:822-828, 1989.
6. Moran MS, Schnitt SJ, Giuliano AE, et al: Society of Surgical Oncology–American Society for Radiation Oncology Consensus Guideline on Margins for Breast-Conserving Surgery With Whole-Breast Irradiation in Stages I and II Invasive Breast Cancer. Ann Surg Oncol. February 10, 2014 (early release online); Int J Radiat Oncol Biol Phys 88:553-564, 2014; J Clin Oncol. February 10, 2014 (early release online).
7. Houssami N, Macaskill P, Marinovich L, et al: The association of surgical margins and local recurrence in women with early-stage invasive breast cancer treated with breast-conserving therapy: A meta-analysis. Ann Surg Oncol. January 29, 2014 (early release online).
8. Holland R, Veling SH, Mravunac M, et al: Histologic multifocality of Tis, T1-2 breast carcinomas. Implications for clinical trials of breast-conserving surgery. Cancer 56:979-990, 1985.
9. Houssami N, Morrow M: Margins in breast conservation: A clinician’s perspective AND what the literature tells us. J Surg Oncol 2014 (in press).
10. Bouganim N, Tsvetkova E, Clemons M, et al: Evolution of sites of recurrence after early breast cancer over the last 20 years: Implications for patient care and future research. Breast Cancer Res Treat 139:603-606, 2013.
11. Anderson SJ, Wapnir I, Dignam JJ, et al: Prognosis after ipsilateral breast tumor recurrence and locoregional recurrences in patients treated by breast-conserving therapy in five National Surgical Adjuvant Breast and Bowel Project protocols of node-negative breast cancer. J Clin Oncol 27:2466-2473, 2009.
