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10.1245/s10434-006-9308-1
Annals of Surgical Oncology 14:1040-1044 (2007)
© 2007 Society of Surgical Oncology
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Original Article

Association of Clinical and Pathologic Variables with Lumpectomy Surgical Margin Status after Preoperative Diagnosis or Excisional Biopsy of Invasive Breast Cancer

Melanie C. Smitt, MD and Kate Horst, MD

Department of Radiation Oncology, Stanford University, 875 Blake Wilbur Dr, Stanford, CA 94305, USA

Correspondence: Address correspondence and reprint requests to: Melanie C. Smitt, MD; E-mail: melanies94028{at}yahoo.com


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Purpose: To evaluate the impact of preoperative diagnosis in obtaining negative lumpectomy margins.

Materials and Methods: Five hundred and thirty five patients who underwent breast conserving therapy for stage I/II cancer from 1971 to 1996 were included in this IRB-approved retrospective analysis. Three hundred and ninety five patients had a defined inked margin status after initial excision. The following factors were evaluated for correlation with margins at initial excision: age (< or >45), grade (3/1 or 2), family history (present/absent), histology (lobular/other), estrogen receptor (ER) status, presence of extensive intraductal carcinoma (EIC), presence of lymphovascular invasion (LVI), and biopsy type (excisional/preoperative).

Results: Biopsy type (P < 0.0001), EIC (P = 0.002), ER status (P = 0.02), lobular histology (P = 0.02) and age (P = 0.02) were significantly correlated with initial margin status among the entire group. For patients who underwent preoperative diagnostic biopsy, 52% (35/67) had negative initial margins as compared to 29% (94/328) for excisional biopsy. Among patients who underwent preoperative biopsy, only lobular histology (P = 0.04) and LVI (P = 0.04) were related to initial margin status. The rate of re-excision was 34% for patients diagnosed preoperatively versus 61% with excisional biopsy (P < 0.0001). The percentage of patients with negative final margin status was similar with either core/needle or excisional biopsy (79 and 78%, respectively).

Conclusions: Preoperative diagnosis is the most significant predictor of initial margin status in patients undergoing breast conservation. Patients with lobular histology may require improved preoperative and/or intraoperative assessment to increase the rate of negative margins at initial excision.

Key Words: Breast cancer • Breast biopsy • Lumpectomy surgical margin


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Core biopsy techniques have become an increasingly preferred method for diagnosis of breast cancer.1–3 The diagnostic sensitivity of this minimally invasive method has established its role in the assessment of nonpalpable breast lesions.4–6 However, it has also been noted that invasive breast cancers diagnosed by core biopsy have lower rates of re-excision after lumpectomy and that management may be more cost-effective compared to open biopsy as a result.7,8 There are limited data on the relationship between various clinicopathologic factors and the surgical outcome of lumpectomy in the setting of preoperative biopsy. This study examines the impact of a variety of these factors in patients undergoing breast conservation. The primary purpose of the study is to evaluate the impact of preoperative diagnosis relative to clinicopathologic factors in obtaining negative lumpectomy margins.


   MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Five hundred and thirty five consecutive patients who underwent breast conservation surgery and radiation for stage I or II breast cancer during the period 1971–1996 were included in this retrospective analysis with IRB approval. Of these, 399 patients had a defined inked margin status after initial excision and pathologic review. Sixty-seven underwent core or fine needle biopsy prior to excision and 328 underwent excisional biopsy for mammographically detected or palpable lesions. The remaining 4 pts underwent incisional biopsy and were excluded from the analysis. Characteristics of the 395 included patients are given in Table 1Go. Policies regarding pathologic review and margin assessment have been previously published.9 One hundred and twenty nine had negative margins at initial excision (no invasive or in situ cancer within 2 mm from the inked margin), and the remainder had close (98) or positive (172) margins. Formal intraoperative pathologic examination was not performed during this timeframe; however, specimen radiographs were generally obtained. The following factors were evaluated for correlation with margins at initial excision: T stage, age (< or >45), grade (3/1 or 2), family history (present/absent), histology (lobular/other), estrogen receptor (ER) status, presence of extensive intraductal carcinoma (EIC), presence of lymphovascular invasion (LVI), and biopsy type (excisional/core or needle) using statistical software with chi-square analysis used to examine associations (SPSS, Inc) with a P value of <0.05 considered significant. The relationships of re-excision and final margin status with biopsy type were also evaluated. As core biopsy was not performed in this group until 1992, a separate analysis was done on all patients treated since 1992 with excisional biopsy (163 pts) or core/fine needle (67) to establish a contemporaneous group. In addition, for patients treated in earlier time periods, certain pathologic variables may not have been routinely assessed and/or slides not available for direct review. However, all pathologic variables were available for analysis in at least 75% of patients in the later time period.


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  		TABLE 1. Patient characteristics of 395 patients with defined margins
 

   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
Significant correlations of initial margin status with clinical and pathologic factors for the entire group and for the group treated since 1992 are shown in Tables 2Go, 3Go, 4Go, 5Go and 6Go. The use of core or needle biopsy was the variable most associated with negative initial margins. Among patients who underwent preoperative biopsy, 52% had negative initial margins as compared to 29% for excisional biopsy. Age less than 45 years, EIC, ER status and lobular histology were also significantly related to initial margin status. The rate of re-excision was 34% for patients diagnosed with core or fine needle biopsy versus 61% with excisional biopsy (P < 0.0001).


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  		TABLE 2. Percentage with negative initial margins by biopsy type
 

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  		TABLE 3. Percentage with negative initial margins by age
 

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  		TABLE 4. Percentage with negative initial margins by presence of EIC
 

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  		TABLE 5. Percentage with negative initial margins by estrogen receptor status
 

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  		TABLE 6. Percentage with negative initial margins by histology
 
For the entire series, more patients had close or negative final margins after preoperative diagnosis than after excisional biopsy (P = 0.03), and more patients had positive final margins after excisional biopsy (P = 0.01) suggesting some variation in re-excision and/or patient selection policies between the two groups. However, for the series of patients treated since 1992, there was no apparent difference in the final margin status for the core/fine needle and open biopsy groups (98 and 95% had negative or close final margins), consistent with a more uniform institutional policy since that time regarding surgical margin status.

Among patients who underwent preoperative diagnostic biopsy, only lobular histology (P = 0.04) and LVI (P = 0.04) were significantly associated with initial margin status. For patients with lobular histology, none (0/4) had negative margins after preoperative biopsy versus 55% (23/63) for non-lobular histology. With LVI, 31% (4/13) had negative margins as compared to 64% (23/36) in the absence of LVI.


   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
In addition to the reduction in use of open surgical procedures for benign breast disease, the use of core biopsy has potential benefits for women diagnosed with breast cancer. Preoperative diagnosis has been associated with the decreased time to treatment, improved achievement of negative margins, and reduced reoperation rates in several studies, potentially leading to greater cost-effectiveness.7,8,10,11 However, the relative reduction in surgical procedures in individual studies depends on institutional guidelines regarding margin status and re-excision as well as the rate of utilization of breast conserving surgery and the proportion of patients with DCIS as compared to invasive cancer. For patients who are not candidates for breast conservation or who wish to have mastectomy, preoperative diagnosis with core or needle biopsy will clearly reduce the number of open procedures performed. The situation for patients undergoing breast conservation has been debated, with some feeling that certain groups of patients, such as those with BIRADS-5 lesions with11 or without12 clustered calcifications, may have less benefit.13 The overall cost-effectiveness of core biopsy depends highly on its sensitivity.14 A single series has evaluated local recurrence rates after core and open biopsy in patients undergoing breast conservation, finding no difference in outcomes.15

Our study of patients with invasive cancer selected for breast conservation confirmed a significant benefit to preoperative diagnosis with stereotactic core or fine needle biopsy in terms of attainment of negative margins at initial surgery and reduced use of re-excision. We found the attainment of negative margins to be 29% after open biopsy, which is similar to values previously reported in the literature from 22 to 45%. Our rate of re-excision after open biopsy, at 61%, was also relatively similar to reported values, ranging between 30.5 and 74%. After preoperative diagnosis, our rate of attainment of negative margins was 52%, as compared to reported values of 63–100%.7,8,10,16 The rate of re-excision after preoperative diagnosis in our study was 34%. Yim reported no re-excisions after core biopsy in their series and Morrow reported only 15% undergoing reoperation.7,11 As use of re-excision will depend on one’s criteria for negative margins and perceived tradeoffs between cosmesis and local control, variability in reported values is somewhat expected. Our criteria for negative margins required >2 mm distance of tumor cells from the inked margin, which may account for the use of re-excision being at the upper end of reported ranges. Looking at consecutive series of patients undergoing core biopsy, others have shown a significant decrease in surgical procedures among patients with invasive and noninvasive cancer undergoing either mastectomy or breast conservation. The average number of surgical procedures per patient is reduced from 1.7–1.9 after open biopsy to 1.1–1.3 after core, and the reoperation rate has been reported to decrease from 67–88% down to 16–25%.8,11,13,16

This study attempted to assess the impact of preoperative diagnosis along with other clinicopathologic factors that may impact the adequacy of excision. A single recently published series by Dillon et al.17 also evaluated several factors along with biopsy type. In their series of 612 patients undergoing breast conservation from 1999 to 2003, they found preoperative diagnosis (P < 0.0001), macroscopic multifocality (P < 0.0001), EIC (P = 0.002), lobular histology (P = 0.024) and tumor size or stage to impact the risk of compromised margins. Age <45 (P = 0.02) and lobular histology (P = 0.07) were related to the risk of finding residual disease at re-excision. However, they defined negative margins as those with a ≥5 mm tumor-margin distance. With a more conventional definition of negative margins for the United States (>2 mm tumor-margin distance), our results confirm the importance of preoperative diagnosis, along with EIC and lobular histology. We also found age and ER status to predict for attainment of negative margins. Macroscopic multifocality was not routinely assessed in our series. Among patients who had preoperative diagnosis, only lobular histology and LVI were related to attainment of negative margins. Others have commented on the difficulty of intraoperative margin assessment for lobular carcinomas.18–21 Further improvements in preoperative and/or intraoperative evaluation may be needed to improve reoperation rates for lobular histology. We did not find EIC to be of import in the setting of preoperative diagnosis; however, others have found a correlation between EIC and lumpectomy margin status following core biopsy.22,23 Considering the relatively small number of patients diagnosed preoperatively in these series, both overall and with EIC, results can be considered preliminary.

There are several limitations of our study. Related to its retrospective nature, the study looks at patients treated over a wide time frame. We attempted to account for this by also analyzing a subgroup of patients who were treated only during the initial years of use of stereotactic core biopsy in our institution. Looking at this group of patients should also reduce any bias introduced by further improvements in imaging, screening, and patient selection related to breast conservation in later years when preoperative diagnosis became more prevalent. In addition, routine pathologic assessment of variables such as EIC and LVI was more uniform in recent years and slides were more often available for review. Nonetheless, it is of interest to note that the likelihood of and predictors of negative surgical margin status after excisional biopsy did not change substantially over a wide time period, suggesting that differences between preoperative diagnosis and excisional biopsy would continue to be preserved even in more recent years. As we restricted our study to patients who underwent breast-conserving therapy for invasive disease, we cannot comment on the impact of preoperative diagnosis for all patient diagnosed with either invasive or noninvasive cancer. Specifically, patients who had persistently positive margins or other pathologic findings inconsistent with breast conservation would not be represented. It is estimated that approximately 10% of patients attempting breast conservation may ultimately undergo mastectomy for these reasons. A detailed cost-effectiveness analysis was beyond the scope of the study. In addition, our database cannot distinguish between stereotactic and ultrasound guided core biopsy, or by nature of presentation.

In summary, our study suggests that preoperative diagnosis is the single most important factor in obtaining negative surgical margins at initial excision and in reducing re-excision rates for patients selecting breast conserving therapy.

Received for publication September 12, 2006. Accepted for publication November 11, 2006.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

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