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Influence of breast cancer margin assessment method on the rates of positive margins and residual carcinoma
The American Journal of Surgery 192 (2006) 538 –540
Presentation
Influence of breast cancer margin assessment method on the rates of positive margins and residual carcinoma Jane E. Méndez, M.D.a,b,*, Wayne W. Lamorte, M.D., Ph.D., M.P.H.c, Antonio de las Morenas, M.D.d, Sandra Cerda, M.D.d, Robert Pistey, M.D.d, Thomas King, M.D., Ph.D.d, Maureen Kavanah, M.D.a,b, Erwin Hirsch, M.D.a, Michael D. Stone, M.D.a,b a
Department of Surgery, Boston Medical Center, Boston University School of Medicine, 88 E. Newton St., D 509, Boston, MA 02118, USA b Department of Surgical Oncology, Boston Medical Center, Boston University School of Medicine, Boston, MA, USA c Surgical Research Division, Boston Medical Center, Boston University School of Medicine, Boston, MA, USA d Department of Pathology, Boston Medical Center, Boston University School of Medicine, Boston, MA, USA Manuscript received April 5, 2006; revised manuscript June 9, 2006 Presented at the 7th Annual Meeting of the American Society of Breast Surgeons, Baltimore, Maryland, April 5–9, 2006
Abstract Background: We hypothesized that the method of breast cancer margin assessment may be associated with different rates of positive margins and residual carcinoma. Methods: A total of 178 breast cancer specimens were divided into 2 groups (A and B) based on the margin assessment method used. Rates of positive margins, re-excision, and residual carcinoma at re-excision were compared and analyzed statistically. Results: At least 1 margin was positive in 64.7% in group A and in 65.2% in group B. At directed re-excision 54% in group A and 51% in group B had residual carcinoma. The lateral margin was positive in 44% in group A compared with 26% in group B (P ⫽ .06). The posterior margin was positive in 19% in group A and in 51% in group B (P ⫽ .001). Conclusions: Two different breast cancer specimen margin assessment methods had comparable rates of positive margins and residual carcinoma at re-excision. Different patterns of specific margin positivity suggest that the method of margin assessment may alter results. © 2006 Excerpta Medica Inc. All rights reserved. Keywords: Breast cancer margin assessment; Breast cancer positive margins; Breast cancer re-excision
A positive surgical margin is found in 32% to 63% of breast cancer excision specimens, and triggers re-excision to reduce the likelihood of local recurrence in patients treated with breast-conservation surgery. Positive margins may lead to multiple re-excisions, which may compromise the cosmetic outcome, or lead to a mastectomy. Even though the concept of surgical margin analysis is straightforward, many specific issues remain controversial [1]. Surgical margin analysis has proved to be a critical component of breastconservation surgery, even though the margin analysis lacks standardization [2]. We hypothesized that the method of breast cancer margin assessment may be associated with * Corresponding author. Tel.: ⫹1-617-414-8090; fax: ⫹1-617-4148081. E-mail address: [email protected]
different rates of reported positive margins and residual carcinoma. A total of 178 breast cancer specimens assessed from May 2004 to October 2005 at Boston Medical Center were divided into 2 groups based on the pathologic margin assessment method used. From May 2004 to January 2005 (group A) the specimen was inked by the surgeon using 6 different color inks (Fig. 1), each designating a specific margin as follows: green lateral; yellow, medial; orange, anterior; black, posterior; red, superior; and blue, inferior. The specimen first was dipped in Bouin’s solution for less than 5 seconds and then placed in formalin overnight. Once the specimen was fixed, perpendicular sections were taken from all the margins in addition to representative sections of tumor and normal breast areas. Margins were reported as distance in millimeters to nearby inked margins. A positive
0002-9610/06/$ – see front matter © 2006 Excerpta Medica Inc. All rights reserved. doi:10.1016/j.amjsurg.2006.06.009
J.E. Méndez et al. / The American Journal of Surgery 192 (2006) 538 –540
2mm
SUPERIOR
LATERAL
Anterior Posterior
539
ANTERIOR MEDIAL
2mm
2mm
2mm
POSTERIOR 2mm 2mm
INFERIOR
GROUP A
GROUP B
Fig. 1. Group A breast cancer specimen margin assessment method. Group B breast cancer specimen margin assessment method.
margin was defined as the presence of invasive or in situ carcinoma within 2 mm of the specified margin. From February to October 2005 (group B) the specimen was oriented by the surgeon with 2 suture markers and submitted to the pathology department. In pathology the specimen was fixed in formalin for at least 6 hours. After this first stage of fixation, 2-mm shaved sections were taken from each of the 6 margins and submitted in separate cassettes (Fig. 1). The remaining specimen was sectioned serially and after a second stage of fixation in formalin of at least 8 hours, representative sections were taken. A positive margin was reported as the presence of any in situ or invasive carcinoma within the 2-mm thick shaved margin. Rates of positive margins, re-excision, and residual carcinoma found on re-excision were compared and analyzed statistically using the chi-square method (SASS). All surgical procedures reviewed were performed by 4 surgeons. All the breast surgical specimens of needle localization procedures (both groups) were compressed. Groups A (n ⫽ 86) and B (n ⫽ 92) were comparable for patient age, tumor type, and presence of lymphovascular invasion. At least 1 margin was positive in 64.7% and 65.2% of specimens assessed in groups A and B, respectively (P ⫽ .94) (Table 1). In patients with positive margins, the re-excision rate was 69% for group A and 78% for group B (P ⫽ .26). Of those who underwent margin specific reexcision, 54% in group A and 51% in group B were found to have residual cancer (P ⫽ .79). Multiple re-excisions, not including mastectomy, were performed in 9.4% in group A and in 11.9% in group B (P ⫽ .59). The lateral margin was positive in 44% in group A compared with 26% in group B (P ⫽ .06) (Table 2). The posterior margin was positive in 19% in group A and in 51% in group B (P ⫽ .001).
Our study showed that the rates of positive margins, re-excision, and carcinoma found at re-excision were comparable for 2 pathologic margin assessment methods. The re-excision rates of 69% (group A) and 78% (group B) were high, with only half of the patients found to have residual carcinoma at re-excision. The decision to re-excise or not to re-excise a positive margin was dependent on multiple issues including the extent of tumor involvement at the margin, whether the dissection already had been extended to the chest wall (pectoralis major muscle fascia) or skin, whether a re-excision was possible given the patient’s breast size, or whether the patient had opted to proceed with a total mastectomy. Multiple factors may contribute to the high rate of positive margins and the variability in the pattern of margin positivity. These include specimen compression and friability and ink running into crevices and/or mixing. With the inking method (group A), the lateral margin (green color) was positive more frequently, possibly secondary to the low viscosity of this ink that permitted it to run into crevices. With the 2-mm shaved margin method (group B), the posterior margin was positive more frequently for reasons that are unclear. The posterior margin was positive in 19% versus 51% when comparing groups A and B. This was the greatest observed difference and probably not random. Dooley and Parker [3] showed that specimen compression increases the incidence of false margin positivity. In their study, the best predictors of true margin positivity were multiple close or positive margins or margin positivity in a direction not associated with specimen ex vivo compression. Our data showed that 2 different margin assessment methods, one that does not involve the use of ink, had
Table 1 Rates of positive margins, re-excisions, and residual carcinomas on re-excision by group
Table 2 Percent positive surgical margin by group
Positive margins, % Re-excision, % Carcinoma on re-excision, % ⬎1 re-excision, %
Group A (n ⫽ 86)
Group B (n ⫽ 92)
P value
64.7 69.1 54.1 9.4
65.2 78.3 51.1 11.9
.94 .26 .79 .59
Lateral Medial Anterior Posterior Superior Inferior
Group A, %
Group B, %
P value
44 27 35 19 27 23
26 42 30 51 32 30
.061 .108 .542 .001 .615 .425
540
J.E. Méndez et al. / The American Journal of Surgery 192 (2006) 538 –540
similar positive margin rates. This suggests that the use of ink is not the main problem resulting in positive margins. Cao et al [4] studied the efficacy of taking multiple separate cavity margins at the time of the lumpectomy as final margins that supersede the oriented lumpectomy margins. They found that cavity margins converted 59% of patients with positive lumpectomy margins into patients with negative margins. Hence, 59% of their patients avoided a re-excision with the increased costs, anxiety, and potential compromised cosmetic outcome secondary to multiple re-excisions. Interestingly, only 55% of patients whose carcinoma was transected at the lumpectomy margin had residual carcinoma in their cavity margin. This finding is consistent with the rate of residual carcinoma found at re-excision in our study: 51% to 54%. We are now using and evaluating the cavity margin assessment method at our institution. Papa et al [5] found that the number of positive margins was strongly predictive of residual carcinoma in the re-excision after lumpectomies with positive margins. They concluded that small, clinically detectable, unifocal tumors could be treated without the need for a further excision. They proposed that eradication of microscopic residual tumor could be accomplished by radiation without re-excision. Negative margin status has become a prerequisite for breast-conserving therapy [6], recognizing that positive
margins contribute to a higher local recurrence rate. Two commonly used methods of margin assessment of breast cancer specimens were associated with comparable rates of at least 1 positive margin. They also were similar in predicting residual carcinoma in the re-excision specimen. The 2 methods, however, were associated with different patterns of specific margin positivity. This variability suggests that the method of margin assessment may alter the final pathologic results and, hence, the ultimate treatment decisions. Surgeons should be cognizant of the limitations intrinsic to margin assessment methods used at their own institutions. References [1] Singletary SE. Surgical margins in patients with early stage breast cancer treated with breast conservation therapy. Am J Surg 2002;184: 383–93. [2] Camp ER, McAuliffe PF, Gilroy JS, et al. Minimizing local recurrence after breast conserving therapy using intraoperative shaved margins to determine pathologic tumor clearance. J Am Coll Surg 2005;201:855– 61. [3] Dooley W, Parker J. Understanding the mechanisms creating false positive lumpectomy margins. Am J Surg 2005;190:606 – 8. [4] Cao D, Lin C, Woo SH, et al. Separate cavity margin sampling at the time of initial breast lumpectomy significantly reduces the need for re-excisions. Am J Surg Pathol 2005;29:1625–32. [5] Papa MZ, Zippel D, Koller M, et al. Positive margins of breast biopsy: is re-excision always necessary? J Surg Oncol 1999;70:167–71. [6] Klimberg VS, Harms S, Korourian S. Assessing margin status. Surg Oncol 1999;8:77– 84.
Presentation
Influence of breast cancer margin assessment method on the rates of positive margins and residual carcinoma Jane E. Méndez, M.D.a,b,*, Wayne W. Lamorte, M.D., Ph.D., M.P.H.c, Antonio de las Morenas, M.D.d, Sandra Cerda, M.D.d, Robert Pistey, M.D.d, Thomas King, M.D., Ph.D.d, Maureen Kavanah, M.D.a,b, Erwin Hirsch, M.D.a, Michael D. Stone, M.D.a,b a
Department of Surgery, Boston Medical Center, Boston University School of Medicine, 88 E. Newton St., D 509, Boston, MA 02118, USA b Department of Surgical Oncology, Boston Medical Center, Boston University School of Medicine, Boston, MA, USA c Surgical Research Division, Boston Medical Center, Boston University School of Medicine, Boston, MA, USA d Department of Pathology, Boston Medical Center, Boston University School of Medicine, Boston, MA, USA Manuscript received April 5, 2006; revised manuscript June 9, 2006 Presented at the 7th Annual Meeting of the American Society of Breast Surgeons, Baltimore, Maryland, April 5–9, 2006
Abstract Background: We hypothesized that the method of breast cancer margin assessment may be associated with different rates of positive margins and residual carcinoma. Methods: A total of 178 breast cancer specimens were divided into 2 groups (A and B) based on the margin assessment method used. Rates of positive margins, re-excision, and residual carcinoma at re-excision were compared and analyzed statistically. Results: At least 1 margin was positive in 64.7% in group A and in 65.2% in group B. At directed re-excision 54% in group A and 51% in group B had residual carcinoma. The lateral margin was positive in 44% in group A compared with 26% in group B (P ⫽ .06). The posterior margin was positive in 19% in group A and in 51% in group B (P ⫽ .001). Conclusions: Two different breast cancer specimen margin assessment methods had comparable rates of positive margins and residual carcinoma at re-excision. Different patterns of specific margin positivity suggest that the method of margin assessment may alter results. © 2006 Excerpta Medica Inc. All rights reserved. Keywords: Breast cancer margin assessment; Breast cancer positive margins; Breast cancer re-excision
A positive surgical margin is found in 32% to 63% of breast cancer excision specimens, and triggers re-excision to reduce the likelihood of local recurrence in patients treated with breast-conservation surgery. Positive margins may lead to multiple re-excisions, which may compromise the cosmetic outcome, or lead to a mastectomy. Even though the concept of surgical margin analysis is straightforward, many specific issues remain controversial [1]. Surgical margin analysis has proved to be a critical component of breastconservation surgery, even though the margin analysis lacks standardization [2]. We hypothesized that the method of breast cancer margin assessment may be associated with * Corresponding author. Tel.: ⫹1-617-414-8090; fax: ⫹1-617-4148081. E-mail address: [email protected]
different rates of reported positive margins and residual carcinoma. A total of 178 breast cancer specimens assessed from May 2004 to October 2005 at Boston Medical Center were divided into 2 groups based on the pathologic margin assessment method used. From May 2004 to January 2005 (group A) the specimen was inked by the surgeon using 6 different color inks (Fig. 1), each designating a specific margin as follows: green lateral; yellow, medial; orange, anterior; black, posterior; red, superior; and blue, inferior. The specimen first was dipped in Bouin’s solution for less than 5 seconds and then placed in formalin overnight. Once the specimen was fixed, perpendicular sections were taken from all the margins in addition to representative sections of tumor and normal breast areas. Margins were reported as distance in millimeters to nearby inked margins. A positive
0002-9610/06/$ – see front matter © 2006 Excerpta Medica Inc. All rights reserved. doi:10.1016/j.amjsurg.2006.06.009
J.E. Méndez et al. / The American Journal of Surgery 192 (2006) 538 –540
2mm
SUPERIOR
LATERAL
Anterior Posterior
539
ANTERIOR MEDIAL
2mm
2mm
2mm
POSTERIOR 2mm 2mm
INFERIOR
GROUP A
GROUP B
Fig. 1. Group A breast cancer specimen margin assessment method. Group B breast cancer specimen margin assessment method.
margin was defined as the presence of invasive or in situ carcinoma within 2 mm of the specified margin. From February to October 2005 (group B) the specimen was oriented by the surgeon with 2 suture markers and submitted to the pathology department. In pathology the specimen was fixed in formalin for at least 6 hours. After this first stage of fixation, 2-mm shaved sections were taken from each of the 6 margins and submitted in separate cassettes (Fig. 1). The remaining specimen was sectioned serially and after a second stage of fixation in formalin of at least 8 hours, representative sections were taken. A positive margin was reported as the presence of any in situ or invasive carcinoma within the 2-mm thick shaved margin. Rates of positive margins, re-excision, and residual carcinoma found on re-excision were compared and analyzed statistically using the chi-square method (SASS). All surgical procedures reviewed were performed by 4 surgeons. All the breast surgical specimens of needle localization procedures (both groups) were compressed. Groups A (n ⫽ 86) and B (n ⫽ 92) were comparable for patient age, tumor type, and presence of lymphovascular invasion. At least 1 margin was positive in 64.7% and 65.2% of specimens assessed in groups A and B, respectively (P ⫽ .94) (Table 1). In patients with positive margins, the re-excision rate was 69% for group A and 78% for group B (P ⫽ .26). Of those who underwent margin specific reexcision, 54% in group A and 51% in group B were found to have residual cancer (P ⫽ .79). Multiple re-excisions, not including mastectomy, were performed in 9.4% in group A and in 11.9% in group B (P ⫽ .59). The lateral margin was positive in 44% in group A compared with 26% in group B (P ⫽ .06) (Table 2). The posterior margin was positive in 19% in group A and in 51% in group B (P ⫽ .001).
Our study showed that the rates of positive margins, re-excision, and carcinoma found at re-excision were comparable for 2 pathologic margin assessment methods. The re-excision rates of 69% (group A) and 78% (group B) were high, with only half of the patients found to have residual carcinoma at re-excision. The decision to re-excise or not to re-excise a positive margin was dependent on multiple issues including the extent of tumor involvement at the margin, whether the dissection already had been extended to the chest wall (pectoralis major muscle fascia) or skin, whether a re-excision was possible given the patient’s breast size, or whether the patient had opted to proceed with a total mastectomy. Multiple factors may contribute to the high rate of positive margins and the variability in the pattern of margin positivity. These include specimen compression and friability and ink running into crevices and/or mixing. With the inking method (group A), the lateral margin (green color) was positive more frequently, possibly secondary to the low viscosity of this ink that permitted it to run into crevices. With the 2-mm shaved margin method (group B), the posterior margin was positive more frequently for reasons that are unclear. The posterior margin was positive in 19% versus 51% when comparing groups A and B. This was the greatest observed difference and probably not random. Dooley and Parker [3] showed that specimen compression increases the incidence of false margin positivity. In their study, the best predictors of true margin positivity were multiple close or positive margins or margin positivity in a direction not associated with specimen ex vivo compression. Our data showed that 2 different margin assessment methods, one that does not involve the use of ink, had
Table 1 Rates of positive margins, re-excisions, and residual carcinomas on re-excision by group
Table 2 Percent positive surgical margin by group
Positive margins, % Re-excision, % Carcinoma on re-excision, % ⬎1 re-excision, %
Group A (n ⫽ 86)
Group B (n ⫽ 92)
P value
64.7 69.1 54.1 9.4
65.2 78.3 51.1 11.9
.94 .26 .79 .59
Lateral Medial Anterior Posterior Superior Inferior
Group A, %
Group B, %
P value
44 27 35 19 27 23
26 42 30 51 32 30
.061 .108 .542 .001 .615 .425
540
J.E. Méndez et al. / The American Journal of Surgery 192 (2006) 538 –540
similar positive margin rates. This suggests that the use of ink is not the main problem resulting in positive margins. Cao et al [4] studied the efficacy of taking multiple separate cavity margins at the time of the lumpectomy as final margins that supersede the oriented lumpectomy margins. They found that cavity margins converted 59% of patients with positive lumpectomy margins into patients with negative margins. Hence, 59% of their patients avoided a re-excision with the increased costs, anxiety, and potential compromised cosmetic outcome secondary to multiple re-excisions. Interestingly, only 55% of patients whose carcinoma was transected at the lumpectomy margin had residual carcinoma in their cavity margin. This finding is consistent with the rate of residual carcinoma found at re-excision in our study: 51% to 54%. We are now using and evaluating the cavity margin assessment method at our institution. Papa et al [5] found that the number of positive margins was strongly predictive of residual carcinoma in the re-excision after lumpectomies with positive margins. They concluded that small, clinically detectable, unifocal tumors could be treated without the need for a further excision. They proposed that eradication of microscopic residual tumor could be accomplished by radiation without re-excision. Negative margin status has become a prerequisite for breast-conserving therapy [6], recognizing that positive
margins contribute to a higher local recurrence rate. Two commonly used methods of margin assessment of breast cancer specimens were associated with comparable rates of at least 1 positive margin. They also were similar in predicting residual carcinoma in the re-excision specimen. The 2 methods, however, were associated with different patterns of specific margin positivity. This variability suggests that the method of margin assessment may alter the final pathologic results and, hence, the ultimate treatment decisions. Surgeons should be cognizant of the limitations intrinsic to margin assessment methods used at their own institutions. References [1] Singletary SE. Surgical margins in patients with early stage breast cancer treated with breast conservation therapy. Am J Surg 2002;184: 383–93. [2] Camp ER, McAuliffe PF, Gilroy JS, et al. Minimizing local recurrence after breast conserving therapy using intraoperative shaved margins to determine pathologic tumor clearance. J Am Coll Surg 2005;201:855– 61. [3] Dooley W, Parker J. Understanding the mechanisms creating false positive lumpectomy margins. Am J Surg 2005;190:606 – 8. [4] Cao D, Lin C, Woo SH, et al. Separate cavity margin sampling at the time of initial breast lumpectomy significantly reduces the need for re-excisions. Am J Surg Pathol 2005;29:1625–32. [5] Papa MZ, Zippel D, Koller M, et al. Positive margins of breast biopsy: is re-excision always necessary? J Surg Oncol 1999;70:167–71. [6] Klimberg VS, Harms S, Korourian S. Assessing margin status. Surg Oncol 1999;8:77– 84.