By Monica J. Smith

A meta-analysis has shown that absolute rates of local recurrence in breast cancer patients unergoing breast-conserving surgery have fallen over time across a range of margin widths, and findings support the current clinical guideline definition of a negative margin as no ink on tumor.

To evaluate how rates of local recurrence (LR) have changed over time and the effect that changes in treatment paradigms have had on LR using various margin definitions, Chirag Shah, MD, the director of Breast Radiation Oncology at Cleveland Clinic in Ohio, and his colleagues from multiple institutions conducted a meta-analysis of studies published between 1996 and 2016.

Their meta-analysis included 38 studies with a total of 54,502 patients. Margins fell into nine cohorts including:

  • positive margins;
  • margins ranging 0 to 1 mm, 0 to 2 mm and 0 to 5 mm;
  • margins of 5 mm or less, more than 2 mm, 0 mm and more than 5 mm; and
  • unknown margins.

“Some studies provided data on more than one of these margin cohorts,” Dr. Shah said.

Margins were defined as positive if invasive cancer or ductal carcinoma in situ were seen at the microscopic surgical margin, and negative if there was either no tumor on ink or a minimum distance from tumor on ink. The researchers used Bayesian logistic mixed effects regression to evaluate the risk of LR in relation to margin status and the four enrollment periods: 1980, 1990, 2000 and 2005.

“The absolute rates of LR decreased for all margin definitions over each of the enrollment periods, which also led to an absolute reduction between margin definitions,” Dr. Shah said.

Relative rates of recurrence were stable despite decreasing rates of LR for each cohort. “Comparing no tumor on ink to less than 5 mm, the relative rate of LR between margin definitions was 0.62, 0.61, 0.61 and 0.61 for each of the four enrollment periods. This was seen for all relative rate combinations,” Dr. Shah said.

The study did not evaluate the individual impact of different improvements in treatment over time.

Dr. Shah and his colleagues concluded that their research supports the use of no tumor on ink as an appropriate margin guideline, and that it suggests many reexcisions for close margins can be avoided.

“Not all positive margins are created equal; some may be positive on a pathology report but actually clinically negative. I think there’s always a risk–benefit discussion in terms of the data we have available, and the dangers of reexcising compared with not reexcising knowing that we will not find cancer in some of these patients who undergo additional surgery,” Dr. Shah said.

He presented the research at the American Society of Breast Surgeons’ Virtual Education Series, held in lieu of the annual meeting.