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Annals of Surgical Oncology 10:48-51 (2003)
© 2003 Society of Surgical Oncology

ORIGINAL ARTICLES

Significance of Linear Extent of Breast Carcinoma at Surgical Margin

Farbod Darvishian, MD, Steven I. Hajdu, MD and Dwight C. DeRisi, MD

From the Departments of Pathology (FD, SIH) and Surgery (DCD), North Shore University Hospital, Manhasset, New York.

Correspondence: Address correspondence and reprint requests to: Steven I. Hajdu, MD, Department of Pathology, North Shore University Hospital, 300 Community Dr., Manhasset, NY 11030; Fax: 516-562-4591; E-mail: shajdu{at}nshs.edu


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Background: Our objective was to correlate the extent of margin positivity and the findings on re-excision specimens of infiltrating mammary carcinoma.

Methods: We selected 50 consecutive cases of infiltrating mammary carcinoma, including both infiltrating ductal carcinoma and infiltrating lobular carcinoma, with positive margins followed by re-excision. Margin positivity was defined as the presence of cancer at the inked margin. The extent of margin positivity was assessed by measuring the linear involvement of the inked margin by the carcinoma.

Results: Twenty-one of 50 cases (42%) showed positive findings on re-excision, including either infiltrating carcinoma or carcinoma in situ or both. Nine of 14 cases (64%) with ductal carcinoma in situ or infiltrating ductal carcinoma on re-excision and 4 of 7 cases (57%) with lobular carcinoma in situ or infiltrating lobular carcinoma on re-excision had initial linear margins >1.0 cm, whereas 28 of 29 cases (96%) with negative findings on re-excision had initial linear margins <1.0 cm.

Conclusions: Linear measurement of the inked margin involved by infiltrating mammary carcinoma can be used as a predictor of findings on re-excisions.

Key Words: Breast carcinoma • Positive margin • Residual carcinoma • Size of carcinoma


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
It is crucial to define the risk factors for local recurrence in patients with breast carcinoma who have had a breast-conserving operation. Age, tumor size, status of the lymph nodes, postoperative radiotherapy, and chemotherapy/hormonal therapy have been cited as determinants of locoregional recurrence.1,2

According to some studies, margin status is the most statistically significant determinant of local recurrence.3,4 It has been generally accepted that margin positivity is defined as the presence of carcinoma at the inked transected breast tissue, although it is recommended that tumor distance from the margin be mentioned in the pathology report. Some authors classify margins as "close" when the tumor is located at <1 mm from the ink.4–6 It has been shown that tumor proximity to the margin is a major determinant of local recurrence. Also, the extent of margin involvement has been correlated with local recurrence.3,7,8 The standard method of measuring the extent of margin involvement is defined by the number of sections containing the tumor and/or the number of low-power fields showing the tumor. In this study, we adopted the actual linear size of the carcinoma at the inked margin as a determinant of the extent of margin involvement and showed its relationship with the findings on re-excision. We also correlated the tumor size and the findings on re-excision.


   MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
We selected 50 consecutive cases of infiltrating mammary carcinomas from the pathology files diagnosed in the course of a year, approximately from April 2001 to March 2002. The criteria of inclusion were the presence of infiltrating ductal carcinoma (IDC) or infiltrating lobular carcinoma (ILC) in the initial excision and positive resection margins. The specimens were inked. Margins were shaved and embedded en face. Re-excision specimens were available on all cases. Re-excision was defined as either an immediate additional margin resection (one-stage operation) or delayed lumpectomy or mastectomy (two-stage operation). A total of 632 slides (13 slides per case) were reviewed on the initial excision to assess the extent of margin positivity. After reviewing the slides, a representative slide with the most extensive margin involvement was selected for evaluation. Margin positivity was defined by the presence of carcinoma at the inked resection margin. Microscopically, the portion of inked margin positive for carcinoma was divided into one, or in case of curved margins, multiple straight lines whose lengths were then measured. Subsequently, the extent of margin involvement was classified into three groups: mild (0.1–0.49 cm), moderate (0.5–0.99 cm), and extensive (>=1.0 cm).

Tumor size in the initial excision was extracted from the pathology gross description. In case of multifocal in situ carcinoma on re-excision, the microscopic size of the most dominant focus was measured.

To evaluate the presence and extent of residual carcinoma in the re-excision specimens, a total of 753 slides (12 slides per case) were reviewed. The type and size of residual carcinoma were documented. Positive finding on re-excision was defined by the presence of ductal carcinoma in situ (DCIS), lobular carcinoma in situ (LCIS), IDC, ILC, or a combination of these.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
Thirty-seven of 50 cases (74%) had IDC and 13 cases (26%) had ILC in the initial excision. Twenty-one cases (42%) showed positive findings on re-excision (Table 1). Of those 21 cases, 14 had IDC and 7 had ILC on the initial excision. Twenty-nine cases showed no residual carcinoma on re-excision. Our results showed that 9 of 14 cases (64%) with IDC and positive re-excision had extensive linear margin positivity (>=1.0 cm). Four of seven cases (57%) with ILC and positive re-excision had extensive linear margin positivity (>=1.0 cm). Of 29 cases with negative re-excision, 28 (96%) had mild to moderate linear margin positivity (<1.0 cm) (Table 2). The only case with negative re-excision, which showed extensive linear margin positivity, was a case of well-circumscribed IDC with pushing borders measuring 1.8 cm. The mean size of linear margin positivity in IDCs and ILCs with positive re-excision and in tumors with negative re-excision was .98 cm, 1.05 cm, and .37 cm, respectively (Table 2).


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  		TABLE 1. Summary of the cases with positive findings on re-excision
 

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  		TABLE 2. Correlation of length of positive margin and size of primary tumor with findings on re-excision
 
Initial tumor size in cases of IDC with positive re-excision (n = 14) ranged from 1.1 to 4.5 cm; six cases (43%) were larger than 2.0 cm. Initial tumor size in cases of ILC with positive re-excision (n = 7) ranged from 1.0 to 2.7 cm with only one case (14%) being >2.0 cm. Twenty-eight of 29 cases (96%) with negative re-excision had an initial tumor size of <=2.0 cm (Table 2). The mean tumor size in IDCs and ILCs with positive re-excision and in tumors with negative re-excison was 1.95 cm, 1.64 cm, and 1.26 cm, respectively.

The extent of residual carcinoma was assessable in 18 of 21 patients (Table 1). Mean age of patients was 57.04 years.


   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
The extent of intraductal carcinoma, status of resection margin, and tumor size have been implicated as determinants of local control in breast cancer patients who have had conservative therapy. Mai et al. showed that in 130 core biopsies those containing DCIS without invasive carcinoma had the highest risk of incomplete resection in subsequent lumpectomies. Most core biopsies with infiltrating carcinoma without an intraductal component were associated with negative margins in subsequent excisions.9 Wazer et al. showed that 60% of cases with initial diagnosis of extensive intraductal carcinoma (EIC) had DCIS on re-excisions. Only 26% of IDCs revealed DCIS on re-excisions.7 In another study the "true recurrence/marginal miss" rate at 5 years was 20% and 7% for cases with EIC and without EIC, respectively.6

Tumor size is another predictor of local recurrence in breast cancer patients. Mirza et al. showed that large tumor size (>1.5 cm) correlated with the development of locoregional recurrence.1 In our study, 6 of 14 cases (43%) with DCIS or IDC in re-excision had initial tumor size of >2.0 cm. None of the re-excisions with DCIS or IDC had an initial tumor size of <=1.0 cm. Twenty-nine of our 50 cases with positive margins had negative findings on re-excision, of which 28 (96%) had tumor size of <=2.0 cm. Only one case with negative re-excision (4%) had an initial tumor size >3.0 cm. The latter case was a 4.0-cm, rather well defined, infiltrating ductal carcinoma with features of medullary carcinoma and pushing borders. Of seven cases with LCIS or ILC on re-excision, six cases showed initial tumor size of <=2.0 cm. We demonstrated that seven of eight tumors (88%) >2.0 cm had positive findings on re-excision (Table 2).

Margins of resection in the histologic examination of breast specimens may be addressed by positivity versus negativity, closest distance from tumor, and extent of involvement. It has been shown that in 50% to 67% of cases with positive margins, the re-excision specimen will have residual carcinoma.3 Frazier et al. showed that 21 of 40 cases (52.5%) with positive margins had residual cancer on re-excision.10 In a study of 262 cases with IDC, the local failure rate was 9% and 1.5% in cases with positive margins and negative margins, respectively.11 Mansfield et al. showed 92% and 84% local control rates at 10 years in patients who had lumpectomies with negative and positive margins, respectively, despite a similar 5-year local control rate.12 Similar results have been shown by Dibiase et al.13 All of the 50 cases we selected for the study had positive margins on initial excision, of which 21 (42%) showed positive findings on re-excision. This rather low rate can be partly explained by lack of long-term follow-up. Nevertheless, even a 42% local failure rate emphasizes the importance of negative margins in achieving local control in breast cancer patients with conservative therapy.

The closest distance of resection margin from the tumor is yet another predictor of local failure. Most authors define a positive margin by the existence of carcinoma at the transected inked margin. Margins within 1 mm of the tumor have been defined as "close".3,4–6,11 Schnitt et al. showed 21%, 4%, and 0% recurrence rates for positive margins, close margins, and negative margins, respectively.6 In a study by Gage et al., ipsilateral breast recurrence rate at 5 years was reported as 2% and 16% for negative/close and positive margins, respectively.4 By examining 469 cases with DCIS, Silverstein et al. concluded that patients with close margins (<1 mm) significantly benefit from postoperative radiotherapy in terms of local recurrence, whereas in patients with wide margins (>=10 mm) additional therapy is unlikely to be of benefit. This result underlines the importance of wide margins in local control of breast carcinoma.14

The significance of LCIS in the initial lumpectomy and/or re-excision is controversial. Sasson et al. showed that LCIS significantly increased the risk of ipsilateral breast tumor recurrence in some patients who were treated with breast-conserving therapy.15 In other studies, however, the locoregional recurrence rate of patients with LCIS was not significantly different than that of patients without LCIS.16,17 We accepted LCIS as a positive finding in re-excision. However, given that all of our cases were recent, we cannot ascertain the impact of this finding on overall patient outcome.

Using a four-tier system, some authors classify the extent of margin involvement into focal, minimal, moderate, and extensive.7,8 This assessment is based on the number of microscopic low-power fields showing the tumor and/or the number of sections containing the tumor. Neuschatz et al. showed that re-excision specimens had positive findings in 30%, 46%, 68%, and 85% in cases with focal, minimal, moderate, and extensive margin positivity, respectively.8 Gage et al. concluded that cases with focally positive margins have a considerably lower risk of local recurrence than those with more than focally positive margins. These authors defined focal positivity by the existence of IDC or DCIS at the margin in three or fewer low-power fields.4 Using the same criteria, Schnitt et al. showed that excisions with focally positive margins and those with more than focally positive margins had "true recurrence/marginal miss" rates of 6% and 21% at 5 years, respectively.6

By measuring the lengths of involved margins, we classified the extent of margin positivity into three groups (Table 2). Our results revealed that 9 of 14 cases (64%) with initial IDC and positive findings on re-excision showed extensive linear margin positivity of >=1.0 cm. Four of seven cases (57%) with initial ILC and positive findings on re-excision showed extensive linear margin positivity. Twenty-eight of 29 cases (96%) with negative findings on re-excision had a linear margin positivity of <1.0 cm (mild to moderate). Twenty of the latter 29 cases (69%) had only mild linear margin positivity (<.5 cm).

We conclude that tumor size and the extent of linear margin positivity directly correlate with local control in breast cancer patients. Given the high local failure rate associated with linear positive margins >1.0 cm, we suggest incorporating the actual size of the linear positive margin in the pathology report as a predictor of local failure. Further studies are needed to demonstrate whether the patients with positive linear margins >1.0 cm will benefit from postoperative radiotherapy more than those with less positive linear margins.


   Footnotes
 
We conducted this study to correlate the extent of linear margin positivity and the findings on re-excision specimens in patients with infiltrating breast carcinoma. Our results showed that the extent of linear margin positivity can be used as a determinant of residual carcinoma in re-excisions.

Received for publication May 28, 2002. Accepted for publication September 6, 2002.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

  1. Mirza NQ, Vlastos G, Meric F, et al. Predictors of locoregional recurrence among patients with early-stage breast cancer treated with breast-conserving therapy. Ann Surg Oncol 2002; 9: 256–65.[Abstract/Free Full Text]
  2. Van Zee KJ, Liberman L, Samli B, et al. Long term follow-up of women with ductal carcinoma in situ treated with breast-conserving surgery. Cancer 1999; 86: 1757–67.[CrossRef][Medline]
  3. Smitt MC, Nowels KW, Zdeblick MJ, et al. The importance of the lumpectomy surgical margin status in long-term results of breast conservation. Cancer 1995; 76: 259–67.[CrossRef][Medline]
  4. Gage I, Schnitt SJ, Nixon AJ, et al. Pathologic margin involvement and the risk of recurrence in patients treated with breast-conserving therapy. Cancer 1996; 78: 1921–8.[CrossRef][Medline]
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  7. Wazer DE, Schmidt-Ullrich RK, Schmid CH, et al. The value of breast lumpectomy margin assessment as a predictor of residual tumor burden. Int J Radiation Biol Phys 1997; 38: 291–9.
  8. Neuschatz AC, DiPetrillo T, Steinhoff M, et al. The value of breast lumpectomy margin assessment as a predictor of residual tumor burden in ductal carcinoma in situ of the breast. Cancer 2002; 94: 1917–24.[CrossRef][Medline]
  9. Mai KT, Chaudhuri M, Perkins DG, Mirsky D. Resection margin status in lumpectomy specimens for duct carcinoma of the breast: correlation with core biopsy and mammographic findings. J Surg Oncol 2001; 78: 189–93.[CrossRef][Medline]
  10. Frazier TG, Wong RW, Rose D. Implications of accurate pathologic margins in the treatment of primary breast cancer. Arch Surg 1989; 124: 37–8.[Abstract]
  11. Anscher MS, Jones P, Prosnitz LR, et al. Local failure and margin status in early-stage breast carcinoma treated with conservation surgery and radiation therapy. Ann Surg 1993; 218: 22–8.[Medline]
  12. Mansfield CM, Komarnicky LT, Schwartz GF, et al. Ten-year results in 1070 patients with stages I and II breast cancer treated by conservative surgery and radiation therapy. Cancer 1995; 75: 2328–36.[CrossRef][Medline]
  13. DiBiase SJ, Komarnicky LT, Schwartz GF, Xie Y, Mansfield CM. The number of positive margins influences the outcome of women treated with breast preservation for early stage breast carcinoma. Cancer 1998; 82: 2212–20.[CrossRef][Medline]
  14. Silverstein MJ, Lagios MD, Groshen S, et al. The influence of margin width on local control of ductal carcinoma in situ of the breast. N Engl J Med 1999; 340: 1455–61.[Abstract/Free Full Text]
  15. Sasson AR, Fowble B, Hanlon AL, et al. Lobular carcinoma in situ increases the risk of local recurrence in selected patients with stage I and II breast carcinoma treated with conservative surgery and radiation. Cancer 2001; 91: 1862–9.[CrossRef][Medline]
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