Our study demonstrates wide variation among surgeons in the Los Angeles county and metropolitan Detroit areas regarding the definition of an adequate negative margin. None of the margin definitions provided (tumor not on ink, > 1–2 mm, > 5 mm, > 1 cm) were endorsed by more than half the respondents when treatment with BCS included radiotherapy, regardless of whether the diagnosis was invasive cancer or DCIS. More specialized surgeons (i.e. > 50% of practice devoted to breast disease) were significantly more likely to endorse smaller margins in the invasive cancer scenario than their non-specialized counterparts, but years in practice and gender did not influence margin preference. Somewhat surprisingly, other measures of surgeon practice were not correlated with attitudes about margin status including affiliation with a specialized cancer treatment setting or the extent of multidisciplinary treatment decision making (presence of a tumor board; extent to which the surgeon discussed treatment plans with other specialists prior to surgery).
Similar variation in the definition of a negative margin has been observed among North American and European radiation oncologists. Taghian et al.13
surveyed 702 North American radiation oncologists and 431 European radiation oncologists. Tumor not touching ink was accepted as a negative margin by 46% of North Americans and only 28% of Europeans. No regional variations in the definition of a negative margin were observed within different parts of the United States, suggesting that our findings from Los Angeles and Detroit are generalizable to surgeons throughout the country. Similar to the findings of our study, Taghian et al.13
did not observe variation in the definition of a negative margin based on practice in an academic or a non-academic setting. We extend this finding as we did not find significant correlations between surgeon attitudes about margin width and factors such as gender, surgeon specialization, institutional specialization, or degree to which the practice has multidisciplinary decision support models.
The lack of consensus in margin definition reflects the lack of a standardized definition of a negative margin in the original randomized trials of BCT. While the NSABP-061
study used the definition of tumor cells not touching ink, other randomized trials appeared to employ more widely clear margins. Entrance criteria for the Institute Gustave Roussy study included a gross margin of 2 cm14
, while the Milan I trial15
specified removal of a “quadrant” of the breast. The use of these gross definitions means that the actual microscopic margin widths in these studies ranged from margins involved with tumor to margins negative by several centimeters depending upon the microscopic extent of disease and the location of the tumor within the quadrant. This unmeasured variation precludes the use of data from the randomized trials to analyze the impact of negative margin width on ipsilateral breast tumor recurrence (IBTR) after controlling for other variables. It is not particularly surprising that retrospective studies have not resulted in consistent findings regarding margin width and IBTR.2
Margin assessment is a sampling of the surface of the lumpectomy specimen, and both the technique of sampling and the number of specimens examined is variable. Wright et al reported that the positive margin rate at Memorial Sloan-Kettering Cancer Center increased from 15% to 49% when the technique of pathologic assessment of margins changed from perpendicular margins to shaved margins, although surgical practice did not change in that interval.16
Graham et al. noted that the mean height of the lumpectomy specimen (anterior to posterior distance) as measured by the surgeon in the operating room was decreased by 54% when measured in the pathology lab when compression devices were used for specimen x-rays, and by 41% when these devices were not used, introducing a major source of variation in the measurement of anterior and posterior margin width.17
In addition, Wiley et al. observed that the likelihood of identifying residual invasive cancer after an initial lumpectomy decreases in a statistically significant way as the time from the initial surgical procedure increases, introducing18
another source of variation in margin assessment.18
Given all these potential sources of variation, it is not surprising that differences of millimeters in margin width have not been shown to correlate with rates of IBTR. In addition, it has become clear that factors other than tumor burden, as measured by margin width, have a major impact on the risk of IBTR. The use of adjuvant systemic therapy significantly reduces IBTR19
, and newer information suggest that the intrinsic biologic subtype of the breast cancer may also be related to the risk of IBTR.20
This is a rapidly evolving field, and it is possible that surgeons who devote a greater proportion of their practice to breast cancer management may be more aware of the impact of factors other than margin width on IBTR than their counterparts who treat breast cancer less frequently, and therefore place less emphasis on obtaining more widely clear margins.
In DCIS the situation is slightly different since the identification of subtypes of DCIS with a different propensity to develop invasive cancer has proven elusive. In the randomized studies that examined the use of RT in DCIS, the only microscopic margin definition employed was tumor not touching the ink21, 22
, so it is reassuring that our study indicates that surgeons who favor this definition for invasive cancer have a similar approach in DCIS treated with RT. The selection of patients with DCIS for treatment without RT remains a matter of controversy. However, a well publicized single institution study21, 23
has suggested that excision to a margin of 1 cm or greater obviates the need for RT in DCIS. Although the results of this study have not been reproduced prospectively24, 25
, it is likely that these data account for the overall preference for more widely clear margins in the scenario of DCIS treated with excision alone. The difference between high and low volume surgeons observed in this scenario, which is in the opposite direction of that observed for patients treated with RT, is not readily explainable but may reflect a greater tailoring of margin status to the individual patient scenario by more specialized surgeons.
Our study has important implications for clinical care. Re-excision rates in the literature are highly variable and range from 20–60%.6, 7
In a population-based study of 800 women attempting BCS in 2006, the procedure was successful in 88%, but 22% required re-excision.8
Re-excision necessitates a second trip to the operating room with its attendant costs, delays the initiation of adjuvant systemic therapy, and leads to patient anxiety. Our results suggest that a significant proportion of re-excisions are done in patients with negative margins (tumor not touching ink) because of the use of alternate margin definitions not supported by consistent high quality clinical data. The variability in margin definition is increasingly being recognized as a problem and led participants in both the 2008 Bidenkopf International Consensus Conference on the Local Therapy of Breast Cancer26
and the 2009 St. Gallen Consensus Conference on Early Stage Breast Cancer to endorse tumor not touching ink as the standard definition of an adequate negative margin in women with invasive carcinoma, and to suggest that margins be considered in the context of multiple factors known to influence the risk of IBTR. Our results suggest that better standards need to be broadly adopted by the surgical community at large because variation in surgeon attitudes was observed across surgeon and practice subgroups.
Our study does have limitations. The margin widths reported are based on surgeon responses to case scenarios and may not reflect actual clinical practice, particularly the use of re-excision when the ideal margin is not achieved. Additionally, the survey population is geographically limited to 2 large metropolitan areas which may not be reflective of United States practice patterns as a whole, although a study examining this issue in the radiation oncology community did not demonstrate differences in margin preference based on geographic location within the United States.13
In spite of these concerns, our study documents clear variation among surgeons in the definition of what negative margin width precludes the need for re-excision. Achieving a more widespread consensus on this issue has the potential to reduce costs, to decrease the use of unnecessary mastectomies, and perhaps to increase patient acceptance of BCS at a time when mastectomy rates are rising.