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10.1245/s10434-006-9246-y
Annals of Surgical Oncology 14:1618-1628 (2007)
© 2007 Society of Surgical Oncology
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Original Article

Factors Affecting Successful Breast Conservation for Ductal Carcinoma in Situ

Mary F. Dillon, MB, MRCSI1, Enda W. Mc Dermott, MCh, FRCSI1,4, Ann O’Doherty, MB, FRCR2,4, Cecily M. Quinn, MD, FRCPath3,4, Arnold D. Hill, MCh, FRCSI2,4 and Niall O’Higgins, MCh, FRSCI1

1 Department of Surgery, St Vincent’s University Hospital, Dublin, Ireland
2 Department of Radiology, St Vincent’s University Hospital, Dublin, Ireland
3 Department of Pathology, St Vincent’s University Hospital, Dublin, Ireland
4 Breastcheck, Merrion unit, National Breast Screening Programme, Dublin, Ireland

Correspondence: Address correspondence and reprint requests to: Mary F. Dillon, MB, MRCSI; Department of Surgery, Education and Research Centre, St Vincent’s University Hospital, Elm Park, Dublin 4, Ireland; E-mail: maryfdillon{at}hotmail.com


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 CONCLUSION
 REFERENCES
 
Background: Successful breast-conserving therapy in DCIS is restricted by high rates of residual disease resulting in the need for radiotherapy and/or re-excision. This study identifies patients with DCIS who are most at risk of compromised margins and of residual disease.

Methods: All patients undergoing breast-conserving surgery for DCIS over a 6-year period were included. Method of diagnosis, mammographic size, pathological size, DCIS-margin distance and residual disease on re-excision were analysed.

Results: One hundred and thirty-five patients underwent initial breast-conserving surgery for DCIS. The compromised margin rate was 72%, and the rate of residual disease on re-operation was 54%. On univariate analysis, underestimation of pathological size by mammography by >1 cm occurred in 40% of those with compromised margins undergoing a therapeutic operation compared to only 14% of those with clear margins (P = 0.02). However, on multivariate analysis only pathological size (P < 0.0001, OR = 1.0,95% CI 1.037–1.128) and lack of a preoperative diagnosis by core biopsy (P < 0.0001, OR = 5.3,95% CI 1.859–15.08) were predictive of compromised margins. The presence of residual disease on re-excision was associated with increasing pathological size (P < 0.0001, OR = 1.085,95% CI 1.038–1.134) and decreasing DCIS-margin distance (P = 0.03, OR = 6.694,95% CI 1.84–37.855). Twenty-nine percent (n = 13/45) of lesions ≤3 cm compared to 84% (n = 27/32) of lesions >3 cm had residual disease on re-operation (P < 0.0001). Residual disease was present in 62% (n = 34/55), 64% (n = 7/11) and 17% (n = 2/12) of patients with DCIS-margin distances ≤1, 1–2 and 2–5 mm, respectively.

Conclusion: Considerable underestimation of DCIS extent by mammography occurs in a high proportion of patients with compromised margins in breast conservation. Patients at particularly high risk of residual disease on re-excision are those with lesions >3 cm and those with DCIS-margin distances of ≤2mm.

Key Words: Breast conserving surgery • Residual tumour • Histopathology • Breast neoplasm


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
METHODS
 RESULTS
 DISCUSSION
 CONCLUSION
 REFERENCES
 
Routine mastectomy for ductal carcinoma in situ (DCIS) is now considered over treatment, and breast conserving therapy has become the principal treatment choice in these patients.1 The success of breast conserving surgery in DCIS has been curtailed by high rates of compromised margins and high rates of residual disease on re-operation.2–8 The importance of clear margins is underscored by substantial evidence that involved margins constitute a highly significant predictor of local recurrence.9–15 Given that the compromised margin rates for DCIS are typically cited at between 55–71%,2,7,8,16,17 there is a clear need for guidelines to identify which patients are most suitable for breast conservation.

In addition, unlike invasive breast carcinoma where radiotherapy post breast conservation is considered mandatory, radiotherapy post excision of DCIS is not always standard practice.18 Furthermore, there is evidence that even when given, radiotherapy may not compensate for lack of re-excision in those with close margins.12,14,19 Where the decision to re-excise and/or refer for radiotherapy is under debate, identifying those patients at high risk of residual disease would aid in planning further treatment.

Finally, there is no consensus worldwide as to what constitutes an adequate DCIS-margin distance in breast conservation for DCIS, with various studies accepting margins anywhere between 1–10 mm as standard.3,6,8,20 This study also focuses on the relationship between precise DCIS-margin width and the presence of residual disease on re-excision in an attempt to gain a pathological assessment of an adequate DCIS-margin width.

The aim of this study was to determine if there were any pathological and radiological factors that identified patients at risk of compromised margins and of residual disease. The second aim of this study was to correlate precise DCIS-margin width with rates of residual disease on re-operation.


   METHODS
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
RESULTS
 DISCUSSION
 CONCLUSION
 REFERENCES
 
The study population comprised 135 patients presenting to the symptomatic (n = 51) and screening services (n = 84) at St Vincent’s University Hospital over a 6-year period (1999–2005) who underwent breast conservation surgery for DCIS. Patients were identified from a database of clinical information relating to these patients. Patients who were referred to a specialist breast clinic by their primary care physicians attended the symptomatic clinic. The screening population was derived from those women attending the Irish National Breast Screening Programme ("BreastCheck"), a population-based screening programme offering mammographic screening to all women aged 50–64 years.

The study population included those who had a preoperative diagnosis by needle core biopsy, and were therefore undergoing a therapeutic surgical procedure. Also included in the study population were patients undergoing surgery without a definitive histological preoperative diagnosis of DCIS. For the purposes of this study, both the total group and those who had a definitive preoperative diagnosis were separately analysed.

Diagnostic and therapeutic excision specimens were examined according to the United Kingdom Royal College of Pathologists Cancer Screening Programme guidelines.21 Each specimen was orientated by the surgeon using metal clips (1 medial, 2 anterior, 3 superior) and sutures (long lateral, short superior, double deep) according to standard protocol. Specimen X-ray was performed in theatre and if calcifications were identified close to or at the radial margin immediate re-excision was carried out. Copies of the specimen X-rays accompanied the specimen to the pathology laboratory. Each specimen was weighed, measured in three-dimensions and differentially inked to facilitate identification of individual margins. Following fixation the specimen was sliced at 3–5 mm intervals perpendicular to the mediolateral axis and individual slice X-rays performed. The slices were inspected and any macroscopic abnormality documented. Using the macroscopic and slice X-ray findings for guidance the lesion was blocked in its entirety and representative blocks of all margins were taken. In specimens where calcifications were the sole abnormality tissue either side of the calcified area was also blocked to ensure the detection of non-calcified DCIS. Separate re-excision specimens taken at the time or during a second procedure were also sliced at 3–5 mm intervals, X-rayed as appropriate and blocked extensively for histological evaluation.

Specimens were also examined microscopically with respect to DCIS extent, grade, architectural pattern, the presence or absence of necrosis, and the presence or absence of microinvasion. The DCIS-margin distance was specified for each margin. The margins were considered compromised if foci of DCIS were found within 10 mm of the radial resection margin. To aid comparisons with international practice, which is quite variable in the definition of compromised margins, separate analysis of compromised margins was also performed using the more conservative definition of ≤2 mm. The presence of lobular carcinoma in situ (LCIS) or atypical ductal or lobular hyperplasia was not considered to affect margin status. Patients whose radial margins (superior, inferior, medial, lateral) were compromised were candidates for re-operation. In patients who did not have a preoperative histological diagnosis, the diagnostic excision was considered as the first operation.

Mammograms were performed using a Siemens Mammomat-B Unit (Erlington, Germany) until June 1999 and a Mammomat 3000 Unit (Erlington, Germany) subsequent to this. All available preoperative mammography was reviewed by a specialist breast radiologist (AOD) who was blinded to the surgical outcome and margin status. The extent of DCIS on mammogram in both longitudinal and transverse planes was measured, as well as recording the presence of calcifications, associated densities or other abnormalities.

Data are presented as median (range) for continuous variables and as frequencies and percents for categorical discrete variables. For categorical variables statistical comparisons between groups are made using chi-square analysis. For normally distributed continuous variables comparisons are made using t test and Mann–Whitney U test for non-normally distributed variables. Correlations between variables are assessed using Pearsons correlation coefficient for normally distributed variables and spearman’s Rho rank order correlation for abnormally distributed variables. Univariate and multivariate analyses were conducted using binary logistic regression with the presence or absence of clear margins and residual disease as the outcome variables. The multivariate model included both theoretically reasonable variables and those variables with univariate P values ≤0.25. The likelihood ratio test and the Nagelkerke R square were used to identify independent variables with low explanatory power and to assess the fit of each specification of the multiple regression models. Statistical analysis was performed with SPSS statistical software (Statistical Package for the Social Sciences, version 11, Chicago, IL, USA).


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
DISCUSSION
 CONCLUSION
 REFERENCES
 
Patient Population
One hundred and thirty-five patients underwent an initial breast conserving procedure for DCIS. Of these, 59% (n = 80) had a definitive diagnosis of DCIS on a preoperative needle core biopsy and were undergoing a therapeutic operation. Forty one percent (n = 55) of patients did not have a histological diagnosis of DCIS pre-operatively and were undergoing a diagnostic operation. The median lesion size was 2 cm (range: 0.1–12 cm), the median age at diagnosis was 55 years (range: 28–79 years).

Compromised Margins (Table 1Go)
Precise margin status was documented in 130 patients. In this cohort, the compromised margin rate following operation was 72% (n = 93). The compromised margin rate for those with a preoperative diagnosis on core biopsy was 63% (n = 50/79) and for diagnostic excisions was 84% (n = 43/51) (P < 0.01).


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  		TABLE 1. Comparison of patients who had clear margins compared to those with compromised margins
 
The demographic and DCIS characteristics of patients with compromised margins and clear margins were compared in Table 1Go using a definition of compromised margins of <10 and ≤2 mm, respectively. Pathological size was significantly higher in patients with compromised margins (P < 0.0001). The rates of compromised margins for each given pathological size are demonstrated in Fig. 1Go. Lesion size ≤3 cm was associated with a compromised margin rate of 61% (n = 55/90) whereas lesion size >3 cm was associated with a compromised margin rate of 95% (n = 35/37) (P < 0.0001.) DCIS grade, architecture or the presence of microinvasion had no affect on compromised margins rates (all P > 0.05). A pre-operative diagnosis by core biopsy was significantly associated with a reduction in the rates of compromised margins (P < 0.01). A separate analysis was conducted on the subgroup of patients who had a definite preoperative diagnosis by core biopsy (data not shown). In this analysis, pathological size was also significantly associated with compromised margins (P < 0.0001).


Figure 1
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  		FIG. 1. Analysis of relationship between tumour and mammographic size and the rate of compromised margins. This analysis uses three different definitions of "compromised margins" as follows: <10 mm [tumour/mammographic size (1)]; ≤2 mm [tumour/mammographic size (2)] and tumour at inked margin [tumour/mammographic size (3)].

 
Radiology
Mammographic size (n = 115) was compared to pathological size. Excluded from the analysis were those patients whose radiology was not available for review (n = 10), whose mammograms were normal (n = 6), or whose pathological size was not accurately documented (n = 4). On univariate analysis, mammographic size was significantly higher in the compromised margins group in both the total population (P = 0.02) and in the cohort who had a preoperative diagnosis by core biopsy (P = 0.03). Figure 1Go shows the association between mammographic size, pathological size, and compromised margins, demonstrating high rates of compromised margins in those patients with mammographic lesions over 3 cm.

The association between mammographic size and pathological size is further demonstrated in Fig. 2Go. There was a significant positive correlation between mammographic size and pathological size (r(rho) = 0.384, P < 0.001). In 11% (n = 13) of patients mammographic size exactly equalled pathological size. Some degree of underestimation and overestimation of disease by mammography occurred in 44% (n = 51) and 44% (n = 51) of patients respectively. Underestimation and overestimation of disease by >1 cm occurred in 25% (n = 29) and 17% (n = 19), respectively.


Figure 2
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  		FIG. 2. Correlation between pathological size and mammogram size.

 
In the subgroup undergoing a therapeutic operation, only 14% (n = 4/28) of those with clear margins had mammographic underestimation of >1 cm compared to 40% (n = 19/47) of those with compromised margins (P = 0.018) (Table 1Go). Similar findings were also demonstrated in the total population with 11% (n = 4/35) of those with clear margins being underestimated by >1 cm by mammography compared to 32% (n = 25/77) of those in the compromised margin group (P = 0.018). Mammographic underestimation of disease on univariate analysis was therefore significantly higher in the group with compromised margins. In contrast, the mammographic descriptive finding of an associated mass/architectural distortion compared to calcification only had no effect on the incidence of compromised margins (Table 1Go).

Multivariate analysis, by logistic regression, was performed to further evaluate factors associated with compromised margins. In this analysis, pathological size (P < 0.0001, OR = 1.0; 95% CI 1.04–1.13) and the absence of a preoperative diagnosis by core biopsy (P = 0.002, OR = 5.3; 95% CI 1.86–15.08) were found to be independently predictive of compromised margins (Table 2Go). The model was also tested using ≤2 mm as the definition of a compromised margin. Pathological size as a continuous (P < 0.0001) and dichotomous variable (P < 0.0001) was also significant in this analysis, as was absence of a preoperative diagnosis by core biopsy (P < 0.0001).


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  		TABLE 2. Univariate and multivariate predictors of compromised margins (<10 mm)*
 
Residual Disease and Re-Operation Rates (Table 3Go)
Of the total sample, 87 patients underwent a second procedure. Re-excision was performed in 89% (n = 25/28) of patients with DCIS at the inked margin and 91% (n = 30/33), 85% (n = 11/13); 100% (n = 12/12) and 29% (n = 2/7) of patients with DCIS-margin distances <1, 1–2, 2–5 and 5–10 mm, respectively. In those that underwent re-excision, 54% (n = 47) had residual disease. The results were similar in the cohort that had a preoperative diagnosis (54%; n = 23/43). Table 3Go compares patient and lesion characteristics between those who did or did not have residual disease on re-operation. On univariate analysis, pathological size, (P < 0.001) mammographic size (P = 0.03), mammographic underestimation of disease (P < 0.05) and DCIS-margin distance (P < 0.001) were factors significantly associated with residual disease. Twenty-nine percent (n = 13/45) of those with pathological lesion sizes <3 cm compared to 84% (n = 27/32) of those >3 cm (P < 0.0001) had residual disease on re operation (Fig. 3Go). The number of margins involved was not associated with residual disease on re-excision (Table 3Go).


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  		TABLE 3. Comparison of patients who had residual disease on re-operation compared to those who did not
 

Figure 3
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  		FIG. 3. Analysis of the relationship between lesion size and the rate of residual disease on re-operation.

 
Decreasing DCIS- margin distance was significantly associated with the presence of residual disease on re-operation. Figure 4Go demonstrates the relationship between DCIS-margin distance and the finding of residual disease on re-operation. Rates of residual disease were as high in those with DCIS-margin distances between 1 and 2 mm as in those with DCIS-margin distances ≤1 mm (62%; n = 34/55 and 64%; n = 7/11, respectively). However, the rates of residual disease at re-operation declined sharply following this, with a rate of 17% (n = 2/12) and 0% (n = 0/2) for those with original DCIS-margin distances of 2–5 mm and 5–10 mm, respectively.


Figure 4
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  		FIG. 4. Relationship of DCIS-margin distance and residual disease on re-operation. * chi-square test for trend

 
Multivariate analysis was performed to further evaluate factors associated with residual disease. In this analysis, both pathological size as a continuous (P < 0.0001, OR = 1.09; 95% CI 1.04–1.13) and dichotomous variable (P < 0.0001, OR = 12.2; 95% CI 3.63–41.1) and DCIS-margin distance (comparing ≤2 mm vs. >2 mm)(OR = 6.69; 95% CI 1.84–37.85) were independently predictive of residual disease (Table 4Go)


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  		TABLE 4. Univariate and Multivariate predictors of residual disease
 
Re-Operation
Of the 87 patients that required re-operation, 71 had one further operation (mastectomy = 26; re-excision = 45), 13 patients had 2 operations and 3 patients had 3 or more operations. The eventual mastectomy rate was 28% (n = 38/135). Those who had a preoperative diagnosis with core biopsy were less likely to have a second operation than those that did not (n = 43/80 vs. n = 44/55; P = 0.002).

Successful Breast Conservation (Tables 5Go & 6Go)
Analysis was also performed on those patients who ultimately underwent successful breast conservation compared to those that did not. On univariate analysis, pathological and mammographic size (P ≤ 0.001), mammographic underestimation of pathological size by >1 cm (P < 0.001), multiple margin involvement (P = 0.04), and DCIS-margin distance (P < 0.001) were factors affecting the likelihood of whether breast conservation was successful or not. On multivariate analysis, pathological size (P < 0.0001) was the only predictor of ultimate success in breast conservation.


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  		TABLE 5. Comparison of patients who ultimately had successful breast conserving surgery compared to those who eventually underwent mastectomy
 

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  		TABLE 6. Univariate and multivariate predictors of unsuccessful breast conservation (i.e. Mastectomy)
 

   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
CONCLUSION
 REFERENCES
 
The management of DCIS has always been controversial. Paradoxically, for a pre invasive disease, mastectomy was the surgery of choice in early years,22 in part because DCIS was considered to be an inherently extensive disease. In recent times, breast conserving therapy (BCT) has become the principle treatment choice.1 However, the success of BCT in DCIS is complicated by high compromised margins rates,2,8,16,17 and high rates of residual disease.2–8 Clear margin status in DCIS is considered fundamental in preventing local recurrence.11,15 However, calls for up to a 10 mm DCIS-margin to satisfy a "clear margin"12,19 status as well as the frequent inability to gain a preoperative diagnosis in DCIS23 means that high re-operations rates are likely to become the norm. In addition, post operative radiotherapy for DCIS is not always standard practice,18 meaning that complete excision, or identifying patients at risk of residual disease is of particular importance.

There is little data available on those at risk of compromised margins, which may help in the formulation of guidelines as to which patients would be most suitable for BCT, or may assist in counselling patients who are likely to require a second procedure. The results of the present study demonstrate that DCIS size is an important predictor of compromised margins. Those at particularly high risk appeared to be those with lesions over 3 cm, whose risk of compromised margins was over 90%. One other author analysed the association of lesion size and compromised margins. Cheng et al.6 found that 77% of patients with DCIS ≥ 2.5 cm had positive margins compared to 30% of those with lesions <2.5 cm. Consequently, the size threshold for recommending breast conservation may be considerably lower in patients with DCIS than that which has been traditional in the guidelines for patients with invasive ductal carcinoma (4–5 cm or stage II disease).24,25 In particular, patients who have lesions over 3 cm should be counselled that if breast conservation is undertaken, that they are at high risk of re-operation. In the present study, we did not find that other variables such as grade, architecture, necrosis, microinvasion, or the presence of a mass or calcification on mammography, were of value in identifying those at high risk. Not surprisingly, having a histological diagnosis with a preoperative core biopsy was found to decrease the risk of compromised margins and reduce the risk of having to undergo a second procedure. Given the benefit in core biopsies in increasing the chances of successful, margin-negative lumpectomy on first operation, and reducing overall the number of operations undertaken23 we would advocate attempting core biopsy in all patients with the suspicion of DCIS.

For pathological size to be of clinical relevance in the preoperative planning of procedures there must be a relationship between imaging and pathological size. It has been suggested that mammographic size can misrepresent pathological size in DCIS with conflicting reports that mammography can underestimate26,27 or overestimate28,29 pathological size. In this study, mammography both underestimated and overestimated extent of disease but when averaged out mammographic size appeared in univariate analysis to be of use in broadly identifying at risk groups. However, on further analysis, it appeared that the propensity for mammography to underestimate disease may be an important contributor to compromised margins. Forty percent of patients with compromised margins undergoing a therapeutic breast conserving surgery had a mammographic underestimation of size >1 cm, compared to only 14% of those with "clear" margins. While this finding was significant only on univariate analysis, the high proportion of patients with compromised margins who also had considerable underestimation of disease mammographically, is important. DCIS is usually impalpable and adequacy of excision assured primarily by specimen X-ray. Therefore, estimates of size by mammography in the context of surgical excision should be viewed with caution, and if cosmetically possible a wider margin attempted beyond the specimen radiograph. That the specimen radiograph is unreliable for determining the probability of residual disease has been shown by Lee et al.5 In her study of invasive and in situ disease, she demonstrated that those patients with calcifications that were completely excised had a 56% rate of residual disease on re-excision. Moreover, 19% of those that had an incomplete excision of calcifications had no residual disease.

Determining which patients are at risk of residual disease may be of greater clinical importance than identifying those at risk of compromised margins. The decision to re-excise margins or to refer patients for radiotherapy may be based on the clinician’s perception of the probable rates of residual disease. Overall, our study population had a 54% rate of residual disease on re-operation, which is similar to the typical rates reported in the literature of 47–76%.2–5,7,8 Other studies have reported that size,6–8 DCIS-margin distance6,8 and extent of disease at margin8 are associated with residual disease on re-excision. In this study, the two principal determinants of residual disease following multivariate analysis were size and DCIS-margin distance. The median pathological size for those with residual disease was 4 cm compared to 2 cm for those with no residual disease. Our results suggest that 3 cm is a critical lesion size in determining the risk of residual disease. Twenty-nine percent of lesions ≤3 cm compared to 84% of lesions >3 cm had residual disease on re-operation. Further excision is therefore of particular importance in all patients with lesions of this size. Cheng et al.6 similarly suggested that high risk lesions were those >2.5 cm in size as they had a 69% rate of residual disease compared to a rate of 28% for lesions between 1.5 and 2.4 cm. However, other studies such as Neuschatz et al.8 and Sigal-Zafrani et al.7 found that a high rate of residual disease was found at even the very smaller lesion sizes. It may be that our attempt to achieve a wider 10 mm margin reduces the rates of residual disease found with smaller lesions.

Other pathological and radiological features were not predictive of residual disease. In this study, we also analysed number of margins involved, as a marker for the extensiveness of the disease at the margins, this was also not found to be significantly associated with residual disease. The effect of grade on residual disease was also analysed. The results of a recent international survey18 suggested that worldwide, grade is highly influential in guiding clinicians in the referral of patients for radiotherapy. In that survey, 52% of clinicians recommend radiotherapy to those with low-grade lesions that have >10 mm clear margins compared to 94% recommending radiotherapy for high-grade lesions. It should be noted however, that in the present study, as in others,7,8 grade had no influence on the rates of residual disease, suggesting that the decision for radiotherapy should not be guided by grade of DCIS.

In a previous study30 we demonstrated the pathological importance of a 5 mm tumour-margin width in invasive ductal carcinoma, as tumour found as far distant from the margin as 2–5 mm had a 45% risk of carcinoma on re-excision. In DCIS there is evidence that adopting a 10 mm margin has benefits in terms of a reduction in local recurrence though as yet, no worldwide consensus has been reached as to what policy in practice should be implemented.31 Similarly, the majority of published reports use a <1 or <2 mm criteria as a "compromised" margin necessitating re-excision.3,4,6,7,12,14,16,31,32 In the current study, those patients who had a DCIS-margin width of 2 mm or less the rate of residual carcinoma on re-excision was over 60%. In those patients with a DCIS-margin distance of 2–5 mm the rate of residual disease was 17%. While rates of residual disease may not translate into recurrence, particularly in centres where post-operative radiotherapy is routine, our results provide a pathological rationale for adopting a 5 mm margin.


   CONCLUSION
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 CONCLUSION
REFERENCES
 
This study has demonstrated that patients undergoing breast conservation for DCIS are at high risk of compromised margins. Those with lesions greater than 3 cm or those with no preoperative diagnosis by core biopsy are at particular risk and should be counselled accordingly. Preoperative mammography can broadly aid the identification of patients at risk, but in a proportion of patients the propensity of mammography to considerable underestimate disease appears to be an important contributor to compromised margins. Wider margins around the extent of the abnormality on the specimen radiograph should therefore be performed if cosmetically feasible. Lesion size and DCIS-margin distance identified those at high risk of residual disease, with 85% of those with lesions >3 cm having residual disease on re-operation. In addition, the results of our study would also support a 5 mm margin as an acceptable DCIS- margin width as the rates of residual disease on re-excision were 62% and 17% for DCIS-margin distances of <2 and 2–5 mm, respectively.


   ACKNOWLEDGMENTS
 
Our thanks to Dr Christina O’Loughlin, PhD for statistical analysis.

Received for publication June 14, 2006. Accepted for publication September 5, 2006.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 CONCLUSION
 REFERENCES
 

  1. Verkooijen HM, Fioretta G, de Wolf C, et al. Management of women with ductal carcinoma in situ of the breast: a population-based study. Ann Oncol 2002; 13:1236–45.[Abstract/Free Full Text]
  2. Mokbel K, Choy C, Leris C, et al. Predictors of positive margins after local excision of ductal carcinoma in situ. Am J Surg 2001; 181:91–5.[CrossRef][Medline]
  3. Silverstein MJ, Gierson ED, Colburn WJ, et al. Can intraductal breast carcinoma be completely excised by local excision? Cancer 1994; 73(12):2985–89.[CrossRef][Medline]
  4. Goldstein NS, Kestin L, Vicini F. Pathological features of initial biopsy specimens associated with residual intraductal carcinoma in situ of the breast referred for breast conserving surgery. Am J Surg Path 1999; 23(11):1340–48.[CrossRef][Medline]
  5. Lee CH, Carter D. Detecting residual tumor after excisional biopsy of impalpable breast carcinoma: efficacy of comparing preoperative mammograms with radiographs of the biopsy specimen. AJR 1995; 164:81–86.[Abstract/Free Full Text]
  6. Cheng L, Al-Kaisi NK, Gordon NH, et al. Relationship between the size and margin status of ductal carcinoma in situ of the breast and residual disease. J Natl Cancer Inst 1997; 89:1356–60.[Abstract/Free Full Text]
  7. Sigal-Zanfrani B, Lewis JS, Clough JB, et al. Histological margin assessment for breast ductal carcinoma in situ: precision and implications. Mod Pathol 2004; 17:81–88.[CrossRef][Medline]
  8. Neuschatz AC, DiPetrillo T, Steinhoff M, et al. The value of breast lumpectomy margin assessment as a predictor of residual tumour burden in ductal carcinoma in situ of the breast. Cancer 2002; 94(7):1917–24.[CrossRef][Medline]
  9. Solin LJ, Fourquet A, Vicini FA, et al. Mammographically detected ductal carcinoma in situ of the breast treated with breast conserving surgery and definitive breast irradiation: long-term outcome and prognostic significance of patient age and margin status. Int J Radiat Oncol Biol Phys 2001; 50:991–1002.[CrossRef][Medline]
  10. Solin LJ, Fourquet A, Vicini FA, et al. Long-term outcome after breast-conservation treatment with radiation for mammographically detected ductal carcinoma in situ of the breast. Cancer 2005; 103(6):1137–46.[CrossRef][Medline]
  11. 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: the effect of age. Cancer 1999; 86(9):1757–67.[CrossRef][Medline]
  12. Chan KC, Knox WF, Sinha G, et al. Extent of excision margin width required in breast conserving surgery for ductal carcinoma in situ. Cancer 2001; 91(1):9–16.[CrossRef][Medline]
  13. Weng EY, Julliard GJ, Parker RG, et al. Outcomes and factors impacting local recurrence of ductal carcinoma in situ. Cancer 2000; 88(7):1643–9.[CrossRef][Medline]
  14. Neuschatz AC, DiPetrillo T, Safaii H, et al. Margin width as a determinant of local control with and without radiation therapy for ductal carcinoma in situ (DCIS) of the breast. Int J Cancer 2001; 96(Suppl):97–104.[CrossRef][Medline]
  15. Cutilli B, Cohen-Solal-le Nir C, de Lafontan B, et al. Breast-conserving therapy for ductal carcinoma in situ of the breast: the French cancer centers’ experience. Int J Radiat Oncol Biol Phys 2002; 53(4):868–79.[CrossRef][Medline]
  16. 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 1988; 318–903.
  17. Douglas-Jones AG, Logan J, Morgan JM, et al. Effects of excision on recurrance after local excision of ductal carcinoma in situ of the breast. J Clin Path 2002; 55(8):581–6.[Abstract/Free Full Text]
  18. Ceilley E, Jagsi R, Goldberg S, et al. The management of ductal carcinoma in situ in North America and Europe. Cancer 2004; 101(9):1958–67.[CrossRef][Medline]
  19. Silverstein MJ, Lagios MD, Groshen S, et al. The influence of margin width on local control of ductal carcinoma in situ of the breast. NEJM 1999; 340(19):1455–61.[Abstract/Free Full Text]
  20. Holland PA, Gandhi A, Knox WF, et al. The importance of complete excision in the prevention of local recurrence of ductal carcinoma in situ. Br J Cancer 1998; 77(1):110–14.[Medline]
  21. The Royal College of Pathologists. NHS Cancer Screening Programmes. Pathology Reporting of Breast Disease. NHS BSP Publication No. 58. 2005. Available: http://www.cancerscreening.nhs.uk/breastscreen/publications/nhsbsp58-high-resolution.pdf.
  22. Skinner KA, Silverstein MJ. The management of ductal carcinoma in situ of the breast. Endocr Relat Cancer 2001; 8(1):33–45.[Abstract]
  23. Dillon MF, Quinn CM, McDermott EW, et al. The diagnostic accuracy of core biopsy for DCIS and its implications for surgical practice. J Clin Path 2006; 59:740–3.[Abstract/Free Full Text]
  24. Morrow M, Strom EA, Bassett LW, et al. Standard for breast conservation therapy in the management of invasive breast cancer. CA Cancer J Clin 2002; 52(5):277–300.[Abstract/Free Full Text]
  25. [no authors listed] Mastectomy or lumpectomy? The choice of operation for clinical stages I and II breast cancer. The steering committee on clinical practice guidelines for the care and treatment of breast cancer. Canadian association of Radiation Oncologists. CMAJ 1998; 158(3):S15–21.[Medline]
  26. Shiraishi A, Kurosaki Y, Maehara T, et al. Extension of ductal carcinoma in situ: histopatological association with MR imaging and mammography. Magn Reson Med Sci 2003; 2(4):159–63.[CrossRef][Medline]
  27. Holland R, Hendriks JH, Verbeek AL, et al. Extent, distribution, and mammographic/histological correlations of breast ductal carcinoma in situ. Lancet 1990; 335:519–22.[CrossRef][Medline]
  28. Menell JH, Morris EA, Dershaw DD, et al. Determination of the presence and extent of pure ductal carcinoma in situ by mammography and MRI. Breast J 2005; 11(6):382–390.[CrossRef][Medline]
  29. Bijker N, Rutgers EJ, Peterse JL, et al. Variations in diagnostic and therapeutic procedures in a multicentre, randomised clinical trial (EORTC 10853) investigating breast conserving treatment for DCIS. Eur J Surg Oncol 2001; 27:135–40.[CrossRef][Medline]
  30. Dillon MF, Hill AD, Quinn CM, et al. A pathological assessment of adequate margin status in breast conservation surgery. Ann Surg Oncol 2006; 13(3):333–9.[Abstract/Free Full Text]
  31. Taghian A, Mohiuddin M, Jagsi R, Golberg S, Ceilley E, Powell S. Current perceptions regarding surgical margin status after breast-conserving therapy: results of a survey. Ann Surg 2005; 241(4):629–39.[CrossRef][Medline]
  32. Rodrigues N, Carter D, Dillon D, et al. Correlation of clinical and pathological features with outcome in patients with ductal carcinoma in situ of the breast treated with breast-conserving surgery and radiotherapy. Int J Radiat Oncol Biol Phys 2002; 54(5):1331–5.[CrossRef][Medline]



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