Wider negative margins do not improve local control for ductal carcinoma in situ or invasive carcinoma when they are treated with lumpectomy and radiation therapy, our recent literature review shows. However, ambiguity regarding margin width in such cases persists, leading to high rates of re-excision.
Changes in our understanding of the biology of local recurrence (LR) have prompted a reexamination of factors determining optimal surgical margins in breast-conserving therapy (BCT). (1)
For many years, tumor burden was thought to be the primary determinant of LR, and the belief that large negative margins improved outcomes was a logical extension of that view. But it is now clear that tumor biology, rather than an arbitrary margin cutoff, is the major determinant of LR. The risk of LR varies with hormone receptor and human epidermal growth factor receptor 2 (HER2) status. (2)
The consensus guidelines adopted in 2014 support a negative margin, defined as “no ink on tumor,” for invasive carcinoma treated with BCT. (2) Since the guidelines were implemented, much progress has been made in decreasing the need for re-excision in women undergoing BCT. A similar review undertaken for ductal carcinoma in situ (DCIS) treated with lumpectomy and radiation therapy (RT) found that a margin of 2 mm minimizes LR risk, likely secondary to differences in tumor growth patterns and the utilization of systemic therapy compared to invasive cancer. (3)
The consensus guidelines should be interpreted as meaning that re-excision is not routinely indicated, not that it will never be indicated. The patient, their tumor biology, and treatment variables influencing the risk of LR must be considered together when developing an individualized treatment plan.
Multiple operations to obtain adequate margins cause substantial stress for patients, have a potential cosmetic disadvantage, and increase healthcare costs. As new therapeutic advances for breast cancer become available, we must continue to investigate whether it is possible to de-escalate surgical approaches and reduce the burden of treatment on patients.
No Ink on Tumor
About five years ago, the Society of Surgical Oncology and the American Society for Radiation Oncology convened a multidisciplinary panel to develop a consensus guideline on the appropriate margin width for minimizing LR risk in patients with invasive cancer who are undergoing BCT and whole-breast radiation therapy.
The panel concluded that a negative margin of no ink on tumor optimizes local control and that the routine practice of performing additional surgery to obtain a wider negative margin was not supported by evidence. The new consensus guideline was presented in October 2013 and published in 2014. It was endorsed by the National Comprehensive Cancer Network, the American Society of Clinical Oncology, the American Society of Breast Surgery, and the St. Gallen International Expert Consensus Group. (2)
The panel members, from 10 cancer centers across the United States, also evaluated the need for wider negative margins within subsets of high-risk patients. Younger age and triple-negative cancers were both independent risk factors for LR. But the evidence showed that tumor biology, not the extent of surgical excision, was associated with worse outcomes: LR rates were similar among women in high-risk groups treated with BCT or mastectomy. (2), (4)
Invasive Breast Cancer Margins: How Much Is Enough?
As mentioned, the no ink on tumor guideline has led to a significant reduction in the use of additional surgery after an initial lumpectomy. At MSK, re-excision rates among women with invasive breast cancer declined significantly, from 21.4 percent before to 15.1 percent (p=0.006) after early adoption of the guideline in January 2014. The use of BCT rose 13 percent over the same period. (5)
In another study at MSK, we investigated the effect of margin width on LR in patients with triple-negative breast cancer who received BCT and analyzed the results for 535 cancers treated. Seventy-one cancers had margins less than or equal to 2 mm, and 464 had margins greater than 2 mm. Notably, there was no difference in the five-year LR rates between the smaller margin group (4.7 percent) and the larger margin group (3.7 percent, p=0.11). (6)
A recent survey examined reoperation trends after an initial lumpectomy for breast cancer before and after the consensus guidelines in more than 3,700 women with stage I and II breast cancer identified in the Georgia and Los Angeles County, California, registries of the Surveillance, Epidemiology, and End Results Program. The investigators looked at the rates of the final surgical procedure (lumpectomy, unilateral mastectomy, bilateral mastectomy), the rates of additional surgery after an initial lumpectomy over time, and reports from 342 surgeons regarding attitudes toward lumpectomy margins. While the 67 percent rate of initial lumpectomy was stable over time, additional surgery after an initial lumpectomy decreased markedly, by 16 percent (p=0.001) from 2013 to 2015, the time of the guideline’s dissemination. Surgeons treating more than 50 breast cancer cases annually were significantly more likely to report a margin of no ink on tumor as adequate (85 percent, n=105) compared to surgeons treating 20 cases or fewer (55 percent; n=131; p<0.001), (7)indicating that there is still room for adopting the consensus guideline at lower volume centers.
DCIS Margins: How Much Is Enough?
The ten-year cause-specific mortality rate for DCIS is under 1 percent after breast-conserving therapy, (8)but optimizing local control is essential because half of all LRs are invasive cancers. (9) The risk of LR for this patient population is affected by age, extent of disease, symptoms, presence of necrosis, margin width, and the use of adjuvant therapy. (1)
Surveys of surgeons and radiation oncologists report a wide range of what constitutes an acceptable margin width, from no ink on tumor to greater than 1 centimeter. There is no uniform negative margin width reported in the literature that is associated with low LR risk in patients with DCIS treated with excision alone. (1) Multiple factors inform the decision for re-excision or radiotherapy for DCIS, including the growth pattern of the lesion, margin width, the patient’s age, tumor size and grade, and the patient’s comfort with recurrence risk.
For women treated with excision alone, the goal is to remove all microscopic disease to minimize the risk of LR. For women undergoing lumpectomy and radiotherapy, an optimal margin leaves a subclinical volume of residual microscopic disease that can be controlled by radiotherapy.
Optimizing Breast Cancer Therapy
As advances in breast cancer surgery and other modalities occur, we will continue to reevaluate whether we can de-escalate treatment approaches to lessen the burden of treatment for patients.
At MSK, we adopted the no ink on tumor consensus guideline early and conducted a study to confirm the benefits for our patients. We also pioneered the de-escalation of axillary dissection in women with invasive breast cancer and sentinel node metastasis (10)following evidence that found no difference in overall survival or nodal recurrence between sentinel lymph node biopsy and complete axillary lymph node dissection.
The diagnosis and treatment of invasive breast cancer requires a collaborative, multidisciplinary approach. (11) At MSK, the breast cancer team evaluates more than 4,500 new breast cancer cases and sees 3,300 surgical inpatients and outpatients annually. Our objective is to create the most effective individualized treatment plan for each patient to optimize outcomes, reduce the burden of treatment, and improve quality of life.
Monica Morrow, MD, FACS, Chief, Breast Service, Department of Surgery, and Anne Burnett Windfohr, Chair, Clinical Oncology, discuss MSK’s evidence-based, leading-edge breast cancer surgical program.
Disclosure: Dr. Morrow has received honoraria from Genomic Health and Roche.
