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Guideline sets standard for adequate margins in ductal carcinoma in situ

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August 15, 2016

ASCO, American Society for Radiation Oncology and Society of Surgical Oncology today issued a consensus guideline that concludes a 2-mm margin should be the standard adequate margin for breast-conserving surgery among patients with ductal carcinoma in situ treated with whole-breast irradiation.

This margin width is associated with low rates of ipsilateral breast tumor recurrence and may reduce re-excision rates, improve cosmetic outcomes and reduce health care spending, according to the guideline, which was simultaneously published in Journal of Clinical Oncology, Practical Radiation Oncology and Annals of Surgical Oncology.

Mariana Chavez-MacGregor

Mariana Chavez-MacGregor

However, the expert panel did not specify an optimal margin width for patients with ductal carcinoma in situ (DCIS) treated with excision alone.

“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, MD, MSc, assistant professor in the departments of breast medical oncology and health services research at The University of Texas MD Anderson Cancer Center, said in a joint press release. “We hope that the guideline also translates into peace of mind for women, who will know that future surgeries may not be needed.”

Margin width

Breast-conserving surgery, followed by whole-breast radiation therapy, serves as the standard of care for women diagnosed with DCIS. This treatment platform is associated with long-term cause-specific survival rates greater than 95%.

Pathologists determine margin widths following surgery by painting the outer tissue surface with ink. Clear, negative or clean margins mean that no cancer cells are present on the outer edge of the tissue, whereas positive margins mean that cancer cells extended to the inked tissue area.

Approximately one-third of women surgically treated for DCIS undergo re-excision, largely due to a lack of consensus on what represents adequate negative margins.

Additional surgery for DCIS can lead to greater health care costs, potential adverse cosmetic outcomes, patient discomfort, surgical complications, and added stress for patients and families.

Monica Morrow, MD

Monica Morrow

The expert panel — co-chaired by Monica Morrow, MD, chief of the breast surgery service at Memorial Sloan Kettering Cancer Center and past president of Society for Surgical Oncology, and Meena S. Moran, MD, professor of therapeutic radiology and director of breast cancer radiotherapy at Yale School of Medicine — reviewed evidence from 20 studies representing 7,883 patients to determine what margin width minimizes the risk for ipsilateral breast tumor recurrence after breast-conserving surgery.

The panel affirmed that positive margins after surgery suggest a potentially incomplete resection and correspond with a higher risk for ipsilateral breast tumor recurrence.

Further, receipt of whole-breast irradiation does not reduce the risk for recurrence in women with positive margins, according to the panel. Research has shown that positive margins increase the 10-year recurrence rate twofold compared with negative margins, regardless of radiation receipt.

With regard to negative margin widths, the panel concluded that a 2-mm margin serves as an adequate margin for women with whole-breast irradiated DCIS. This margin significantly decreased ipsilateral breast tumor recurrence compared with 0- or 1-mm margins (OR = 0.51; 95% CI, 0.31-0.85).

Surgeons should use judgment and consult with patients when considering re-excision in patients with negative margin widths smaller than 2 mm, according to the panel.

“Factors felt to be important to consider include assessment of ipsilateral breast tumor recurrence risk (residual calcifications on postexcision mammography, extent of DCIS in proximity to margin, which margin is close), cosmetic impact of re-excision, and overall life expectancy,” Morrow and colleagues wrote.

Other guideline recommendations

Some women with DCIS choose to forego radiation therapy in favor of surgical treatment alone. However, a meta-analysis of DCIS trials conducted by the Early Breast Cancer Trialists’ Collaborative Group found that women treated with excision alone had significantly higher rates of ipsilateral breast tumor recurrence, regardless of whether they had negative margins (26% vs. 12%, P < .00001) or positive margins (48.3% vs. 24.2%, P = .00004).

Based on the available data, the researchers did not issue a definitive recommendation for adequate margin width in women undergoing excision alone.

“Treatment with excision alone, regardless of margin width, is associated with substantially higher rates of ipsilateral breast tumor recurrence than treatment with excision and whole-breast irradiation, even in predefined low-risk patients,” the panel wrote. “The optimal margin width for treatment with excision alone is unknown, but should be at least 2 mm. Some evidence suggests lower rates of recurrence with margin widths wider than 2 mm.”

Endocrine therapy appears to decrease recurrence risk in patients with positive margins, but no evidence shows a link between endocrine therapy and reduced recurrence risk in women with negative margins, according to the guideline.

In addition, several factors have historically been associated with ipsilateral breast tumor recurrence, including younger age, histologic tumor pattern, comedo necrosis, and nuclear grade and size.

“However, there are no data addressing whether margin widths should be influenced by these factors, and this represents an appropriate area for further study,” the panel wrote.

The expert panel further recommended that women diagnosed with invasive cancer with a DCIS component should continue to follow joint guidelines issued by Society of Surgical Oncology and American Society for Radiation Oncology regarding invasive cancer treatment.

“[T]he natural history and treatment of these lesions is more similar to invasive cancer than DCIS, even when the close margin contains DCIS,” the panel wrote. “In particular, the vast majority of patients with invasive cancer receive systemic therapy, which remains less common for pure DCIS.”

Moving forward

The panel acknowledged several limitations of their recommendations. Because the recommendations focused on evidence from women treated with whole-breast radiation therapy, they should not be generalized to women treated with accelerated partial-breast irradiation.

The panel further acknowledged that all studies included in their meta-analysis were retrospective analyses.

“However, in the absence of any planned prospective randomized trials addressing the question of margin width and local recurrence, these studies represent the best available evidence for clinical decision-making,” the panel wrote.

In the jointly issued press release, Morrow urged women with negative margins for whom re-excision is recommended to ask their surgeons what factors prompted the recommendation.

Bruce Haffty

Bruce G. Haffty

Bruce G. Haffty, MD, FASTRO, professor and chair of radiation oncology at Rutgers University Robert Wood Johnson Medical School, associate director of the Cancer Institute of New Jersey and immediate past chair of American Society for Radiation Oncology’s board of directors, agreed the guideline will benefit clinicians who struggled with determining adequate margin width in these patients.

“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,” Haffty said. – by Cameron Kelsall

Disclosure: The researchers report no relevant financial disclosures.

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Brigid Killelea

This guideline will be very useful for breast surgeons because it gives us a clear answer to a question that the community has struggled with for some time. It can sometimes be difficult for a surgeon operating on a patient with ductal carcinoma in situ (DCIS) to get clear margins, because the tumor is not always as easy to see or feel as an invasive tumor. We often rely on mammograms or intraoperative X-rays of calcifications to guide us, but none of those techniques are perfect. This guideline gives us a reference point to go by in the operating room, and something we can discuss with our patients when the subject of going back for re-excision comes up.

In general, we have been moving in the direction of 2-mm margins for some time. Most breast surgeons know that a positive margin is something we cannot leave, with the potential exception of positive posterior margins. When there is a little more tissue to take, it is reasonable to use judgment and discuss the potential for re-excision. This guideline shows that with good surgery and whole-breast radiation therapy, the recurrence rate is fairly low.

Cosmetic outcomes are understandably at the forefront of many patients’ minds. This is especially true if the surgeon needs to go back and take more tissue. In most cases, the outcomes are not really altered, and we can achieve an acceptable cosmetic result without having to initiate a mastectomy.

There has been much discussion about acceptable margins, and this issue has received a lot of attention in recent years. A prior consensus statement that told us no tumor in ink — or any negative margin — was OK for invasive breast cancer turned out to be very helpful in practice. As with that instance, we now have a more concrete guideline to approach surgery for DCIS.

Brigid Killelea, MD, MPH, FACS

Smilow Cancer Hospital

Yale School of Medicine

Disclosure: Killelea reports no relevant financial disclosures.