New Guideline Clarifies Surgical Margins in Treating Breast Cancer

For patients with ductal carcinoma in situ (DCIS) who are undergoing breast conserving surgery with whole breast irradiation (WBRT), a 2-mm margin should be the standard, according to a new guideline jointly released by the American Society for Clinical Oncology (ASCO), the American Society for Radiation Oncology (ASTRO) and the Society of Surgical Oncology (SSO).

The guideline, designed to provide clarity regarding the optimal negative margin width for DCIS — a disease that accounts for approximately 20 percent of breast cancer cases — was published in Annals of Surgical Oncology, Practical Radiation Oncology and the Journal of Clinical Oncology. It was also designed to limit patients from undergoing unnecessary surgery while simultaneously reducing healthcare costs.

For negative margin widths, the guideline recommendations state that margins of at least 2 mm are associated with a reduced risk of ipsilatereal breast tumor recurrence (IBTR). Evidence does not support the routine practice of obtaining negative margin widths wider than 2 mm, the panelists stated in the guideline.

“The use of a 2-mm margin as the standard for an adequate margin in DCIS treated with whole breast radiation therapy is associated with low rates of recurrence of cancer in the breast and has the potential to decrease re-excision rates, improve cosmetic outcome and decrease health care costs,” the organizations wrote in the joint statement. “Clinical judgment should be used in determining the need for further surgery in patients with negative margins less than 2 mm. Margins more widely clear than 2 mm do not further reduce the rates of recurrence of cancer in the breast and their routine use is not supported by evidence.”

Additionally, the recommendations state that a positive margin, defined as ink on DCIS, is associated with a significant increase in IBTR that is not nullified through WBRT.

Treatment with excision alone, regardless of margin width, was found to be associated with substantially higher rates of IBTR versus treatment with excision and WBRT, even in predefined low-risk patients, the panel found. Optimal margin width for treatment with excision alone is unknown, but should be at least 2 mm. Additional evidence suggests lower rates of IBTR may be associated with margin widths wider than 2 mm.

Endocrine therapy, however, was found to have reduced IBTR rates, but no evidence exists of an association between endocrine therapy and negative margin width.

The guideline initiative was composed of a panel of experts from each of the organizations, and included clinicians, researchers and patient advocates. The panel examined the relationship between margin width and disease recurrence in approximately 30 studies.

In one such meta-analysis, researchers conducted a comparison of specific margin width thresholds — 2, 3 or 5 and 10 mm — relative to negative margins defined as wider than 0 or one mm in 7,883 patients with a median follow-up of 6.5 years. Here, the predicted 10-year IBTR probability for 2-mm—negative margins was 10.1 percent compared with 8.5 percent for 3- or 5-mm, and 11.7 percent for 10-mm margins.

“An important finding from the review of the published literature performed to provide evidence for this guideline is that margin widths greater than 2 mm (approximately one-eighth of an inch) do not reduce the risk of cancer recurring in the breast in women with DCIS who are treated with lumpectomy and whole breast radiation therapy," Monica Morrow, past president of SSO, panel co-chair, and chief of Breast Service in the Department of Surgery at Memorial Sloan Kettering Cancer Center, said in a statement.

In an October 2015 study published in Annals of Surgery, researchers aimed to evaluate the relationship between margin width and recurrence for breast conserving surgery in DCIS while adjusting for numerous other factors that affect recurrence while stratifying the use of radiation.

In the review, 2,996 cases were identified, of which 363 recurred. The median follow-up for women without recurrence was 75 months (range, 0-30 years); 732 were studied for 10 years. Controlling for age, family history, presentation, nuclear grade, number of excisions, radiotherapy, endocrine therapy and year of surgery, margin width was significantly associated with recurrence in the entire population.

Results showed that larger negative margins were associated with a lower hazard ratio compared with positive margins. An interaction between radiotherapy and margin width was significant. While the association of recurrence with margin width was significant in those without radiotherapy, it was not for those with radiotherapy.

Approximately one in three patients with DCIS who receive surgical treatment undergo a re-excision, partly due to the lack of consensus on what constitutes an adequate negative margin, the organizations said in their statement. Re-excisions can be associated with a cause for patients having double mastectomies, as well as added discomfort and stress, surgical complications, compromise in cosmetic outcome, and increased healthcare costs.

“With this guideline, it is our two-pronged goal to help physicians improve the quality of care they provide to women undergoing surgery for DCIS and ultimately improve outcomes for those patients,” Mariana Chavez-MacGregor, a panel member representing ASCO, and an assistant professor in the Department of Health Services Research, Division of Cancer Prevention, The University of Texas MD Anderson Cancer Center, in a statement. “We hope the guideline also translates into peace of mind for women who will know that future surgeries may not be needed.”

The new guideline, which has also been endorsed by the American Society of Breast Surgeons, is said to assist physicians who struggle with margin width in patients with DCIS. In light of the consensus, patients who have negative margins are encouraged to discuss with their surgeons why, if applicable, a re-excision is necessary.

“This important cooperative guideline generated by these societies involved a multidisciplinary panel of surgical, medical and radiation oncologists, as well as pathologists and statistical experts,” said Bruce G. Haffty, a past chair of ASTRO’s board of directors, and chairman, associate director of the Rutgers Cancer Institute of New Jersey, in a statement. “While the guideline appropriately allows for some flexibility and clinical judgment in interpretation, the conclusion that a 2-mm margin width is adequate in patients with DCIS will be helpful and reassuring to clinicians and patients in clinical decision-making."