Surgical margins in lumpectomy for breast cancer--bigger is not better.

Survival after breast-conserving surgery, which consists of removal of the primary tumor and a margin of surrounding normal tissue (“lumpectomy”) and whole-breast irradiation, has been shown in six prospective, randomized trials to be equivalent to that after mastectomy.1-6 Minimizing tumor recurrence in the breast (local recurrence) is of major clinical importance, since local recurrence is associated with reduced survival and emotional distress.7 Remarkably, more than 20 years after these randomized trials, the most appropriate amount of normal breast tissue that should be removed (the surgical margin width) to minimize local recurrence remains controversial. The status of the surgical margin is assessed by applying ink to the surface of the lumpectomy specimen and determining the microscopic distance between tumor cells and the inked surface. The margin is negative if there is no ink on any cancer cells and positive if there is ink. The microscopic margin width is the closest distance of an inked surface to any tumor cells. In surveys of surgeons and radiation oncologists, no single margin width was endorsed by more than 50% of the respondents.8,9 As a consequence, 20 to 30% of women who undergo breast-conserving surgery require additional breast surgery (reexcision) after the initial lumpectomy, with its associated illness and cost.10,11 Approximately half of these procedures are performed in women with negative margins to obtain a wider clear margin in the belief that a wider margin will further decrease the risk of local recurrence. Among the six randomized trials that established the efficacy of breast-conserving surgery and irradiation, the only one in which the microscopic margin width of the lumpectomy specimen was evaluated was the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-06 trial3; in this trial, patients were required to have a negative margin of no ink on cancer cells to participate in the study. In the other five trials,1,2,4-6 the margin requirement for entry was complete macroscopic removal of the tumor; the actual microscopic margin status (negative or positive) was unknown. A meta-analysis of 21 retrospective studies examining the effect of various margin widths on local recurrence in 14,571 patients with breast cancer showed an odds ratio for local recurrence of 2.42 (P<0.001) with positive margins, but it did not identify a statistically significant difference in local recurrence rates associated with margin widths of more than 1 mm, more than 2 mm, or more than 5 mm after adjustment for the use of a radiation boost or endocrine therapy.12 One difficulty in attempting to assess the effect of small differences (such as 1 mm) in margin width on local recurrence is the lack of standardization of specimen processing, particularly the rigor of evaluation of microscopic margins among pathology laboratories. However, the lack of identification of a significant difference in local recurrence rates between margins of 1 mm and 5 mm12 is difficult to attribute to differences in specimen processing. When considering the best margin width, it is useful to remember that a negative margin of any width does not indicate the absence of residual unresected tumor in the breast13; it simply suggests that the residual tumor burden is probably low enough to be controlled with radiotherapy. Even mastectomy, which provides the largest margin that can be obtained, does not eliminate local recurrence; this indicates that residual disease burden is not the sole determinant of local control. Rates of local recurrence after breast-conserving surgery have decreased considerably since the initial randomized trials. In the NSABP B-06 trial, conducted in the 1970s, the 20-year recurrence rate in the ipsilateral breast was 14.3%.3 In contrast, in NSABP trials conducted in the 1990s, 10-year local recurrence rates ranged from 3.5% to 6.5% among patients treated with breastconserving surgery.14 Although improvements Surgical Margins in Lumpectomy for Breast Cancer — Bigger Is Not Better