Lack of Understanding of Margin Width Remains a Hindrance in DCIS

Kimberly Van Zee, MD

“There is no clearly acceptable answer to the question of what is the appropriate margin for DCIS (ductal carcinoma in situ),” said Kimberly Van Zee, MD, of Memorial Sloan Kettering Cancer Center, in her presentation yesterday at the 33rd Annual Miami Breast Cancer Conference. Van Zee discussed findings from her review of 3000 cases of women treated with breast conserving surgery over 30 years, as well as other studies.

DCIS is common and accounts for roughly 20% of breast cancer cases currently, and local recurrence rates remain substantial, Van Zee said.

“We know that negative margins are clearly a factor that’s associated with a lower risk of recurrence; the problem with all of our randomized trials and many retrospective studies is that margins have been categorized as positive or negative, so that doesn’t help us in determining what the optimal negative margin is,” Van Zee said.

In addition, radiation plays an important role in preventing recurrence, but there’s a need for more data about whether certain patients might be better served without it, she said.

“There has never been a subset of patients identified for which radiation doesn’t reduce the rate of recurrence. But, it’s a proportional reduction. In every subset, radiation reduces risk by about half. The idea is if we find someone with low risk—maybe for about half of them—a reduction of 50% isn’t worth it,” Van Zee said.

The impact of radiation in DCIS was illustrated by the Early Breast Cancer Trialists Collaborative Group’s overview of randomized trials of radiotherapy in DCIS of the breast, from 2010, Van Zee noted. Among those with positive margins, 10-year recurrence rates were 43.8% for those who received no radiation and 24.2% for those who did. For those with negative margins, the respective values were 26% and 12%, Van Zee noted.

“Among people who didn’t get radiation in the overview, there was an absolute benefit of about 18% to have negative margins versus positive margins. And among those with radiation, similarly, there was an important reduction in risk associated with negative versus positive,” Van Zee said.

“But this still doesn’t answer the question of how wide the optimal negative margin is,” she said.

For physicians awaiting clarity on that issue, there is a draft consensus statement that is currently being reviewed by the Society for Surgical Oncology, ASCO, and the American Society for Radiation Oncology. That statement is expected to be released within the next year, said Van Zee, adding, “unfortunately, due to the few data out there about margin width in the absence of radiation, the consensus statement will not include a guideline for that. It will be for radiation.”

In her own study (Ann Surg. 2015;262:623—631) from October last year, Van Zee said the aim was to evaluate the relationship between margin width and recurrence for breast conserving surgery in DCIS while adjusting for numerous other factors that also affect recurrence, while stratifying for use of radiation.

According to the review, 2996 cases were identified, of which 363 recurred. 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 (RT), endocrine therapy, and year of surgery, margin width was significantly associated with recurrence in the entire population. Larger negative margins were associated with a lower hazard ratio compared with positive margins. An interaction between radiotherapy (RT) and margin width was significant (P <.03); the association of recurrence with margin width was significant in those without RT (P < .0001), but not in those with RT (P =.95).

Van Zee concluded that, adjusting for other factors related to recurrence, “wider margin width is associated with a lower risk of recurrence among women not undergoing radiation,” and “wider negative margin width is not associated with a significantly lower risk of recurrence among women receiving radiation.” “Wider negative margins may not be necessary in those that receive radiation,” she said.

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