- Email: [email protected]
Lumpectomy margins are affected by tumor size and histologic subtype but not by biopsy technique
The American Journal of Surgery 188 (2004) 399 – 402
Scientific paper
Lumpectomy margins are affected by tumor size and histologic subtype but not by biopsy technique Anees B. Chagpar, M.D., M.Sc.a,*, Robert C.G. Martin II, M.D.a, Lee J. Hagendoorn, B.S.b, Celia Chao, M.D.c, Kelly M. McMasters, M.D., Ph.D.a a
Department of Surgery, University of Louisville, 315 E. Broadway, Suite #312, Louisville, KY 40202, USA b Advertek, Inc., Louisville, KY, USA c Department of Surgery, The University of Texas Medical Branch, Galveston, TX, USA Manuscript received May 19, 2004; revised manuscript June 6, 2004
Presented at the Fifth Annual Meeting of the American Society of Breast Surgeons, March 31–April 4, 2004, Las Vegas, Nevada
Abstract Objective: The effect of the type of biopsy (needle vs. excisional) on lumpectomy margin status has not been well established. The objective of this study was to determine whether needle biopsy is associated with a higher positive margin rate at time of lumpectomy. Methods: We evaluated this hypothesis in the setting of a prospective multi-institutional study. A total of 3975 patients were enrolled in the University of Louisville Breast Cancer Sentinel Lymph Node Study from May 7, 1998 to June 3, 2003. Patients who underwent lumpectomy at the time of their sentinel lymph node biopsy were the focus of this analysis. Patients with clinical stage T1 N0 and T2 N0 breast cancer were eligible; 29 patients were found to have T3 tumors on final pathology. Pathologists at each institution defined margin positivity, and tumor at the inked margin of resection was the study guideline. Results: Median patient age was 59 years, and median tumor size was 1.5 cm. A total of 2658 patients underwent lumpectomy with the following results. The cancer of 1515 patients was diagnosed by fine-needle or core-needle biopsy and of 821 patients was diagnosed by excisional biopsy; in 322 patients the method of diagnosis was unknown. The type of previous biopsy did not significantly affect the positive-margin rate at the time of lumpectomy (13.3% vs. 11.0% for needle and excisional biopsy, respectively, P ⫽ 0.107). However, patients with larger tumors were more often found to have a positive margin (11.4% vs. 13.9% vs. 27.6% for T1, T2, and T3 tumors, respectively; P ⫽ 0.010). No difference was found in margin status after excision of palpable versus nonpalpable tumors (10.6% vs. 10.9%, respectively, P ⫽ 0.743). Histologic subtype, however, did affect margin status (15.8% vs. 9.8% positive margins for lobular vs. ductal type, respectively, P ⫽ 0.003). Conclusions: In this multi-institutional study, increasing tumor size and lobular histologic subtype were associated with a greater likelihood of a positive margin. The type of biopsy, needle or excisional, had no effect on the ability to achieve negative margins. © 2004 Excerpta Medica, Inc. All rights reserved. Keywords: Biopsy; Breast cancer; Lumpectomy; Margins
The trend toward early diagnosis with widespread screening mammography, coupled with increased patient demand for minimally invasive and cosmetically superior surgical results, has prompted many to argue that breastconserving therapy should be the procedure of choice in women with breast cancer. It has been well established from prospective randomized controlled trials that * Corresponding author. Tel.: ⫹1-502-629-6950; fax: ⫹1-502-6293813. E-mail address: [email protected]
lumpectomy with radiation therapy is equivalent to mastectomy in terms of survival [1,2]. Nonetheless, breast conservation is associated with a higher rate of local recurrence than mastectomy. It is also recognized that the status of the resection margins is a significant predictor of local recurrence [3–13]. The factors that affect margin status are not clearly known. In particular, the impact of the type of biopsy performed has long been debated. Some have argued that the chances of obtaining negative margins after an excisional biopsy for diagnosis are greater than after a needle
0002-9610/04/$ – see front matter © 2004 Excerpta Medica, Inc. All rights reserved. doi:10.1016/j.amjsurg.2004.06.020
400
A.B. Chagpar et al. / The American Journal of Surgery 188 (2004) 399 – 402
biopsy. Although this usually requires 2 operations (1 for diagnosis and 1 for therapeutic excision), it has been a routine surgical practice for decades. Others, however, believe that needle biopsy provides a preoperative diagnosis, which allows for better planning of definitive excision and decreased need for a second excision. Nonetheless, lumpectomy with a negative margin in all planes after needle biopsy sometimes can be difficult to achieve, especially for nonpalpable lesions that require wire localization. There is also a theoretical risk of seeding of tumor cells along the biopsy track with percutaneous needle biopsy. Although it is clear that margin status is important in the management of patients who opt for breast-conserving surgery, the factors that influence margin positivity are not well known. In particular, whether the type of biopsy impacts margin status is unclear. Therefore, the objective of this study was to determine the impact of various clinicopathologic variables, including biopsy technique, on margin status.
Methods The University of Louisville Breast Sentinel Lymph Node Study is a multi-institutional prospective study in which ⬎300 general surgeons from both private and academic practices participated. Patients with clinical stage T1 N0 and T2 N0 cancer were eligible for this study. From August 1997 to June 2003, 3975 patients were enrolled in this study, 2658 of whom underwent lumpectomy as their definitive surgical procedure. These patients formed the population of interest for this study. Data regarding patient demographics, method of diagnosis, and clinicopathologic variables were collected in a prospective fashion. Pathologists at each center defined margin positivity; however, the study guideline used the National Surgical Adjuvant Breast and Bowel Project standard of tumor at the inked margin of resection to considered a margin as positive. A number of clinicopathologic features were examined to determine which factors influenced margin status. These included patient age, tumor size, palpability of the tumor, histology (ductal versus lobular), and biopsy type. Univariate analyses were performed to determine if any of these features significantly impacted margin status. In addition, a multivariate analysis using a logistic regression analysis was also performed. Statistical analysis was performed using MINITAB Release 13.32 (Minitab, State College, PA).
Results Median patient age in this study was 59 years (range 27 to 100), and median tumor size was 1.5 cm (range 0.1 to 9.0). The clinicopathologic features of the patient population in this study are listed in Table 1. Of the 2658 patients who underwent lumpectomy in this study, 329 (12.4%) had
Table 1 Clinicopathologic features of patient population Features
No. of patients (%)
Tumor size* T1 T2 T3 Palpable Yes No Histology Ductal Lobular Other Biopsy technique FNA CNB Excisional Other
1982 (74.6) 583 (21.9) 29 (1.1) 1290 (48.5) 1368 (51.5) 1578 (59.4) 144 (5.4) 936 (35.2) 186 (7.0) 1329 (50.0) 821 (30.9) 322 (12.1)
* Tumor size unknown in 64 patients (2.4%). CNB ⫽ cure-needle biopsy; FNA ⫽ fine-needle aspiration biopsy.
a positive margin. Cancer was diagnosed by fine-needle aspiration biopsy (FNA), by core-needle biopsy (CNB), or by excisional biopsy. The positive-margin rate associated with each of these diagnostic techniques is listed in Table 2. No statistically significant difference in positive-margin rate was noted between percutaneous (FNA or CNB) and excisional biopsy (P ⫽ 0.107). However, FNA was associated with a significantly greater positive margin rate compared with CNB (P ⫽ 0.009). Core biopsy was found to be as effective as excisional biopsy in achieving negative margins (P ⫽ 0.311). A number of other clinicopathologic features were examined in a univariate analysis to determine their impact on Table 2 Margin status associated with clinicopathologic variables Features Tumor size* T1 T2 T3 Palpable Yes No Histologic type Ductal Lobular Other Biopsy technique FNA CNB Excisional Other
Positive-margin rate (%)
P value 0.010
226/1982 (11.4) 81/583 (13.9) 8/29 (27.6) 0.695 163/1290 (12.6) 166/1368 (12.1) 0.035† 180/1578 (11.4) 25/144 (17.4) 124/936 (13.3) 0.107‡ 36/186 (19.4) 165/1329 (12.4) 90/821 (11.0) 38/322 (13.4)
* Tumor size unknown in 64 patients (2.4%). † P value for comparison of ductal versus lobular histologic type. ‡ P value for FNA and CNB versus excisional biopsy. CNB ⫽ cure-needle biopsy; FNA ⫽ fine-needle aspiration biopsy.
A.B. Chagpar et al. / The American Journal of Surgery 188 (2004) 399 – 402 Table 3 Multivariate analysis of determinants of margin status Predictor
Odds ratio (95% confidence interval)*
P value†
Age Tumor size (as a continuous variable) Lobular histologic subtype (vs. ductal) Palpable (vs. nonpalpable) Excisional biopsy technique (vs. FNA and CNB)
1.00 (0.99–1.01) 0.80 (0.72–0.89) 0.61 (0.38–0.97) 1.05 (0.81–1.35) 1.21 (0.91–1.59)
0.555 ⬍0.001 0.036 0.716 0.184
* A value ⬍1 indicates greater chance of positive margins. † Tests the null hypothesis that there is no association between the clinicopathologic variables and obtaining negative margins after adjusting for all other “X” variables in the model. CNB ⫽ cure-needle biopsy; FNA ⫽ fine-needle aspiration biopsy.
margin status. These features included tumor size, palpability, and histologic subtype. These data are listed in Table 2. Based on this univariate analysis, tumor size and histologic subtype were found to be significantly correlated with margin status. We then performed a multivariate analysis to determine which features were independent predictors of margin status. Age, tumor size, palpability, histologic subtype, and biopsy technique were all evaluated in the model. We found that tumor size and histologic subtype remained significant in the model. The type of biopsy (needle vs. excisional) was not significant in this model. Results of this multivariate analysis are listed in Table 3. However, when FNA was compared with CNB and excisional biopsy in a multivariate analysis, FNA remained a significant independent predictor of positive margins (odds ratio ⫽ 0.60; 95% confidence interval 0.39 to 0.91, P ⫽ 0.170).
Comments It has been clearly established that margin status is critical in the management of patients treated with breastconserving therapy. Positive margins have been associated with a higher incidence of local recurrence [3–13] and, in some studies, decreased survival [4,5]. Factors that may be associated with positive margins at the time of lumpectomy have not been clearly elucidated in the literature. A number of studies have found that increasing tumor size is associated with positive margins [3,5,12,14,15]; however, others have not found this to be the case [9,11]. Histologic subtype has also been found to affect margin status in some studies [14 –16] but not in others [3,5,12]. In our large series of 2658 patients treated with lumpectomy, we found that tumor size and histologic subtype were the only 2 factors that correlated with margin status on multivariate analysis. In patients with large tumors or those with known lobular histology, surgeons should be cognizant of the fact that these fea-
401
tures are associated with a higher rate of positive margins and therefore may mandate a wider initial resection. Our main objective, however, was to address the controversy regarding preoperative biopsy type and its impact on surgical margins. Several studies have previously suggested that preoperative FNA is associated with a lower positivemargin rate than excisional biopsy [14,15,17]. In addition, several studies have found that preoperative CNB may decrease the positive margin rate [18 –20]. This has been attributed to the fact that when given the preoperative knowledge of the diagnosis of invasive breast cancer, surgeons are likely to take wider margins. In contrast, Morrow et al [21] found a significantly higher positive margin rate in patients undergoing lumpectomy after CNB than after excisional biopsy (15.7% vs. 2.1%, P ⫽ 0.0001). However, these investigators found that patients whose cancer was diagnosed with a core needle biopsy were more likely to undergo a single surgical procedure than those cancer was diagnosed with excisional biopsy (83% vs. 45%, p ⬍0.001) [21]. Although Lieberman et al [20] also found that patients whose cancer was diagnosed with CNB were more likely to require only 1 surgical procedure than those whose cancer was diagnosed with excisional biopsy (84% vs. 29%, P ⬍0.00001), their study failed to demonstrate any difference in margin positivity between the 2 techniques (8% vs. 5%, P ⫽ 0.7). In our prospective study, we found no difference in positive-margin rate between patients with cancer diagnosed by needle biopsy (defined as FNA or CNB) versus those with cancer diagnosed by excisional biopsy. This is concordant with other studies finding that biopsy technique does not impact local recurrence rates in patients undergoing breast-conserving therapy [22]. However, we found it curious that FNA was associated with a higher positivemargin rate than either core or excisional biopsy in our series. The key factors affecting margin status, however, are tumor size and histologic subtype. Because this information is available before surgery based on physical examination, imaging, and biopsy, definitive surgery can be planned while taking these issues into account. CNB allows a minimally invasive biopsy that has the advantage over FNA of determining whether the malignancy is invasive. Given the fact that this procedure does not adversely affect margin status, our data support the use of percutaneous CNB in the diagnostic evaluation of breast cancer patients.
References [1] Fisher B, Anderson S, Bryant J, et al. Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer. N Engl J Med 2002;347:1233– 41. [2] Veronesi U, Cascinelli N, Mariani L, et al. Twenty-year follow-up of a randomized study comparing breast-conserving surgery with radical mastectomy for early breast cancer. N Engl J Med 2002;347:1227– 32.
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[3] Park CC, Mitsumori M, Nixon A, et al. Outcome at 8 years after breast conserving surgery and radiation therapy for invasive breast cancer: influence of margin status and systemic therapy on local recurrence. J Clin Oncol 2000;18:1668 –75. [4] Meric F, Mirza NQ, Vlastos G, et al. Positive surgical margins and ipsilateral breast tumor recurrence predict disease-specific survival after breast-conserving therapy. Cancer 2003;97:926 –33. [5] DiBiase SJ, Komarnicky LT, Schwartz GF, et al. The number of positive margins influences the outcome of women treated with breast preservation for early stage breast carcinoma. Cancer 1998;82:2212– 20. [6] Swanson GP, Rynearson K, Symmonds R. Significance of margins of excision on breast cancer recurrence. Am J Clin Oncol 2002;22:438 – 41. [7] 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. [8] Ghossein NA, Alpert S, Barba J, et al. Importance of adequate surgical excision prior to radiotherapy in local control of breast cancer in patients treated conservatively. Arch Surg 1992;127:411–5. [9] Spivack B, Khanna MM, Tafra L, et al. Margin status and local recurrence after breast conserving surgery. Arch Surg 1994;129: 952–7. [10] Renton SC, Gazet JC, Ford HT, et al. The importance of the resection margin in conservative surgery for breast cancer. Eur J Surg Oncol 1996;22:17–22. [11] Horiguchi J, Iino Y, Takei H, et al. Surgical margin and breast recurrence after breast conserving therapy. Oncol Rep 1999;6:135– 8. [12] Obedian E, Haffty BG. Negative margin status improves local control in conservatively managed breast cancer patients. Cancer J Sci Am 1999;6:28 –33.
[13] Cowen D, Houvenaeghel G, Bardou VJ, et al. Local and distant failures after limited surgery with positive margins and radiotherapy for node-negative breast cancer. Int J Radiat Oncol Biol Phys 2000; 47:305–12. [14] Tartter PI, Bleiweiss IJ, Levchenko S. Factors associated with clear biopsy margins and clear reexcision margins in breast cancer specimens form candidates for breast conservation. J Am Coll Surg 1997; 185:280 –5. [15] Mai KT, Yazdi HM, Isotalo PA. Resection margin status in lumpectomy specimens of infiltrating lobular carcinoma. Breast Cancer Res Treat 2000;60:29 –33. [16] Luu HH, Otis CN, Reed WP et al. The unsatisfactory margin in breast cancer surgery. Am J Surg 1999;178:362– 6. [17] Cox CE, Reintgen DS, Nicosia SV, et al. Analysis of residual cancer after diagnostic breast biopsy: an argument for fine-needle aspiration cytology. Ann Surg Oncol 1995;2:201– 6. [18] Kaufman CS, Delbecq R, Jacobson L. Excising the reexcision: stereotactic core-needle biopsy decreased the need for reexcision of breast cancer. World J Surg 1998;22:1023– 8. [19] King TA, Cederborn J, Champaign JL, et al. A core breast biopsy diagnosis of invasive carcinoma allows for definitive treatment planning. Am J Surg 1998;176:497–501. [20] Lieberman L, Fahs MC, Dershaw DD, et al. Impact of stereotaxic core breast biopsy on cost of diagnosis. Radiology 1995;195:633–7. [21] Morrow M, Venta L, Stinson T, Bennett C. Prospective comparison of sterotactic core biopsy and surgical excision as diagnostic procedures for breast cancer patients. Ann Surg 2001;233:537– 41. [22] King TA, Hayes DH, Cederbom GJ, et al. Biopsy technique has no impact on local recurrence after breast conserving therapy. Breast J 2001;7:19 –24.
Scientific paper
Lumpectomy margins are affected by tumor size and histologic subtype but not by biopsy technique Anees B. Chagpar, M.D., M.Sc.a,*, Robert C.G. Martin II, M.D.a, Lee J. Hagendoorn, B.S.b, Celia Chao, M.D.c, Kelly M. McMasters, M.D., Ph.D.a a
Department of Surgery, University of Louisville, 315 E. Broadway, Suite #312, Louisville, KY 40202, USA b Advertek, Inc., Louisville, KY, USA c Department of Surgery, The University of Texas Medical Branch, Galveston, TX, USA Manuscript received May 19, 2004; revised manuscript June 6, 2004
Presented at the Fifth Annual Meeting of the American Society of Breast Surgeons, March 31–April 4, 2004, Las Vegas, Nevada
Abstract Objective: The effect of the type of biopsy (needle vs. excisional) on lumpectomy margin status has not been well established. The objective of this study was to determine whether needle biopsy is associated with a higher positive margin rate at time of lumpectomy. Methods: We evaluated this hypothesis in the setting of a prospective multi-institutional study. A total of 3975 patients were enrolled in the University of Louisville Breast Cancer Sentinel Lymph Node Study from May 7, 1998 to June 3, 2003. Patients who underwent lumpectomy at the time of their sentinel lymph node biopsy were the focus of this analysis. Patients with clinical stage T1 N0 and T2 N0 breast cancer were eligible; 29 patients were found to have T3 tumors on final pathology. Pathologists at each institution defined margin positivity, and tumor at the inked margin of resection was the study guideline. Results: Median patient age was 59 years, and median tumor size was 1.5 cm. A total of 2658 patients underwent lumpectomy with the following results. The cancer of 1515 patients was diagnosed by fine-needle or core-needle biopsy and of 821 patients was diagnosed by excisional biopsy; in 322 patients the method of diagnosis was unknown. The type of previous biopsy did not significantly affect the positive-margin rate at the time of lumpectomy (13.3% vs. 11.0% for needle and excisional biopsy, respectively, P ⫽ 0.107). However, patients with larger tumors were more often found to have a positive margin (11.4% vs. 13.9% vs. 27.6% for T1, T2, and T3 tumors, respectively; P ⫽ 0.010). No difference was found in margin status after excision of palpable versus nonpalpable tumors (10.6% vs. 10.9%, respectively, P ⫽ 0.743). Histologic subtype, however, did affect margin status (15.8% vs. 9.8% positive margins for lobular vs. ductal type, respectively, P ⫽ 0.003). Conclusions: In this multi-institutional study, increasing tumor size and lobular histologic subtype were associated with a greater likelihood of a positive margin. The type of biopsy, needle or excisional, had no effect on the ability to achieve negative margins. © 2004 Excerpta Medica, Inc. All rights reserved. Keywords: Biopsy; Breast cancer; Lumpectomy; Margins
The trend toward early diagnosis with widespread screening mammography, coupled with increased patient demand for minimally invasive and cosmetically superior surgical results, has prompted many to argue that breastconserving therapy should be the procedure of choice in women with breast cancer. It has been well established from prospective randomized controlled trials that * Corresponding author. Tel.: ⫹1-502-629-6950; fax: ⫹1-502-6293813. E-mail address: [email protected]
lumpectomy with radiation therapy is equivalent to mastectomy in terms of survival [1,2]. Nonetheless, breast conservation is associated with a higher rate of local recurrence than mastectomy. It is also recognized that the status of the resection margins is a significant predictor of local recurrence [3–13]. The factors that affect margin status are not clearly known. In particular, the impact of the type of biopsy performed has long been debated. Some have argued that the chances of obtaining negative margins after an excisional biopsy for diagnosis are greater than after a needle
0002-9610/04/$ – see front matter © 2004 Excerpta Medica, Inc. All rights reserved. doi:10.1016/j.amjsurg.2004.06.020
400
A.B. Chagpar et al. / The American Journal of Surgery 188 (2004) 399 – 402
biopsy. Although this usually requires 2 operations (1 for diagnosis and 1 for therapeutic excision), it has been a routine surgical practice for decades. Others, however, believe that needle biopsy provides a preoperative diagnosis, which allows for better planning of definitive excision and decreased need for a second excision. Nonetheless, lumpectomy with a negative margin in all planes after needle biopsy sometimes can be difficult to achieve, especially for nonpalpable lesions that require wire localization. There is also a theoretical risk of seeding of tumor cells along the biopsy track with percutaneous needle biopsy. Although it is clear that margin status is important in the management of patients who opt for breast-conserving surgery, the factors that influence margin positivity are not well known. In particular, whether the type of biopsy impacts margin status is unclear. Therefore, the objective of this study was to determine the impact of various clinicopathologic variables, including biopsy technique, on margin status.
Methods The University of Louisville Breast Sentinel Lymph Node Study is a multi-institutional prospective study in which ⬎300 general surgeons from both private and academic practices participated. Patients with clinical stage T1 N0 and T2 N0 cancer were eligible for this study. From August 1997 to June 2003, 3975 patients were enrolled in this study, 2658 of whom underwent lumpectomy as their definitive surgical procedure. These patients formed the population of interest for this study. Data regarding patient demographics, method of diagnosis, and clinicopathologic variables were collected in a prospective fashion. Pathologists at each center defined margin positivity; however, the study guideline used the National Surgical Adjuvant Breast and Bowel Project standard of tumor at the inked margin of resection to considered a margin as positive. A number of clinicopathologic features were examined to determine which factors influenced margin status. These included patient age, tumor size, palpability of the tumor, histology (ductal versus lobular), and biopsy type. Univariate analyses were performed to determine if any of these features significantly impacted margin status. In addition, a multivariate analysis using a logistic regression analysis was also performed. Statistical analysis was performed using MINITAB Release 13.32 (Minitab, State College, PA).
Results Median patient age in this study was 59 years (range 27 to 100), and median tumor size was 1.5 cm (range 0.1 to 9.0). The clinicopathologic features of the patient population in this study are listed in Table 1. Of the 2658 patients who underwent lumpectomy in this study, 329 (12.4%) had
Table 1 Clinicopathologic features of patient population Features
No. of patients (%)
Tumor size* T1 T2 T3 Palpable Yes No Histology Ductal Lobular Other Biopsy technique FNA CNB Excisional Other
1982 (74.6) 583 (21.9) 29 (1.1) 1290 (48.5) 1368 (51.5) 1578 (59.4) 144 (5.4) 936 (35.2) 186 (7.0) 1329 (50.0) 821 (30.9) 322 (12.1)
* Tumor size unknown in 64 patients (2.4%). CNB ⫽ cure-needle biopsy; FNA ⫽ fine-needle aspiration biopsy.
a positive margin. Cancer was diagnosed by fine-needle aspiration biopsy (FNA), by core-needle biopsy (CNB), or by excisional biopsy. The positive-margin rate associated with each of these diagnostic techniques is listed in Table 2. No statistically significant difference in positive-margin rate was noted between percutaneous (FNA or CNB) and excisional biopsy (P ⫽ 0.107). However, FNA was associated with a significantly greater positive margin rate compared with CNB (P ⫽ 0.009). Core biopsy was found to be as effective as excisional biopsy in achieving negative margins (P ⫽ 0.311). A number of other clinicopathologic features were examined in a univariate analysis to determine their impact on Table 2 Margin status associated with clinicopathologic variables Features Tumor size* T1 T2 T3 Palpable Yes No Histologic type Ductal Lobular Other Biopsy technique FNA CNB Excisional Other
Positive-margin rate (%)
P value 0.010
226/1982 (11.4) 81/583 (13.9) 8/29 (27.6) 0.695 163/1290 (12.6) 166/1368 (12.1) 0.035† 180/1578 (11.4) 25/144 (17.4) 124/936 (13.3) 0.107‡ 36/186 (19.4) 165/1329 (12.4) 90/821 (11.0) 38/322 (13.4)
* Tumor size unknown in 64 patients (2.4%). † P value for comparison of ductal versus lobular histologic type. ‡ P value for FNA and CNB versus excisional biopsy. CNB ⫽ cure-needle biopsy; FNA ⫽ fine-needle aspiration biopsy.
A.B. Chagpar et al. / The American Journal of Surgery 188 (2004) 399 – 402 Table 3 Multivariate analysis of determinants of margin status Predictor
Odds ratio (95% confidence interval)*
P value†
Age Tumor size (as a continuous variable) Lobular histologic subtype (vs. ductal) Palpable (vs. nonpalpable) Excisional biopsy technique (vs. FNA and CNB)
1.00 (0.99–1.01) 0.80 (0.72–0.89) 0.61 (0.38–0.97) 1.05 (0.81–1.35) 1.21 (0.91–1.59)
0.555 ⬍0.001 0.036 0.716 0.184
* A value ⬍1 indicates greater chance of positive margins. † Tests the null hypothesis that there is no association between the clinicopathologic variables and obtaining negative margins after adjusting for all other “X” variables in the model. CNB ⫽ cure-needle biopsy; FNA ⫽ fine-needle aspiration biopsy.
margin status. These features included tumor size, palpability, and histologic subtype. These data are listed in Table 2. Based on this univariate analysis, tumor size and histologic subtype were found to be significantly correlated with margin status. We then performed a multivariate analysis to determine which features were independent predictors of margin status. Age, tumor size, palpability, histologic subtype, and biopsy technique were all evaluated in the model. We found that tumor size and histologic subtype remained significant in the model. The type of biopsy (needle vs. excisional) was not significant in this model. Results of this multivariate analysis are listed in Table 3. However, when FNA was compared with CNB and excisional biopsy in a multivariate analysis, FNA remained a significant independent predictor of positive margins (odds ratio ⫽ 0.60; 95% confidence interval 0.39 to 0.91, P ⫽ 0.170).
Comments It has been clearly established that margin status is critical in the management of patients treated with breastconserving therapy. Positive margins have been associated with a higher incidence of local recurrence [3–13] and, in some studies, decreased survival [4,5]. Factors that may be associated with positive margins at the time of lumpectomy have not been clearly elucidated in the literature. A number of studies have found that increasing tumor size is associated with positive margins [3,5,12,14,15]; however, others have not found this to be the case [9,11]. Histologic subtype has also been found to affect margin status in some studies [14 –16] but not in others [3,5,12]. In our large series of 2658 patients treated with lumpectomy, we found that tumor size and histologic subtype were the only 2 factors that correlated with margin status on multivariate analysis. In patients with large tumors or those with known lobular histology, surgeons should be cognizant of the fact that these fea-
401
tures are associated with a higher rate of positive margins and therefore may mandate a wider initial resection. Our main objective, however, was to address the controversy regarding preoperative biopsy type and its impact on surgical margins. Several studies have previously suggested that preoperative FNA is associated with a lower positivemargin rate than excisional biopsy [14,15,17]. In addition, several studies have found that preoperative CNB may decrease the positive margin rate [18 –20]. This has been attributed to the fact that when given the preoperative knowledge of the diagnosis of invasive breast cancer, surgeons are likely to take wider margins. In contrast, Morrow et al [21] found a significantly higher positive margin rate in patients undergoing lumpectomy after CNB than after excisional biopsy (15.7% vs. 2.1%, P ⫽ 0.0001). However, these investigators found that patients whose cancer was diagnosed with a core needle biopsy were more likely to undergo a single surgical procedure than those cancer was diagnosed with excisional biopsy (83% vs. 45%, p ⬍0.001) [21]. Although Lieberman et al [20] also found that patients whose cancer was diagnosed with CNB were more likely to require only 1 surgical procedure than those whose cancer was diagnosed with excisional biopsy (84% vs. 29%, P ⬍0.00001), their study failed to demonstrate any difference in margin positivity between the 2 techniques (8% vs. 5%, P ⫽ 0.7). In our prospective study, we found no difference in positive-margin rate between patients with cancer diagnosed by needle biopsy (defined as FNA or CNB) versus those with cancer diagnosed by excisional biopsy. This is concordant with other studies finding that biopsy technique does not impact local recurrence rates in patients undergoing breast-conserving therapy [22]. However, we found it curious that FNA was associated with a higher positivemargin rate than either core or excisional biopsy in our series. The key factors affecting margin status, however, are tumor size and histologic subtype. Because this information is available before surgery based on physical examination, imaging, and biopsy, definitive surgery can be planned while taking these issues into account. CNB allows a minimally invasive biopsy that has the advantage over FNA of determining whether the malignancy is invasive. Given the fact that this procedure does not adversely affect margin status, our data support the use of percutaneous CNB in the diagnostic evaluation of breast cancer patients.
References [1] Fisher B, Anderson S, Bryant J, et al. Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer. N Engl J Med 2002;347:1233– 41. [2] Veronesi U, Cascinelli N, Mariani L, et al. Twenty-year follow-up of a randomized study comparing breast-conserving surgery with radical mastectomy for early breast cancer. N Engl J Med 2002;347:1227– 32.
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