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Role of sentinel lymph node biopsy in high-risk ductal carcinoma in situ patients
The American Journal of Surgery 194 (2007) 172–175
Clinical surgery–International
Role of sentinel lymph node biopsy in high-risk ductal carcinoma in situ patients Cathal J. Moran, F.R.C.S.I.a, Malcolm R. Kell, M.D., F.R.C.S.I.a,*, Fidelma L. Flanagan, M.D., F.R.C.R.b, Maria Kennedy, M.R.C.Pathc, Thomas F. Gorey, M.Ch., F.R.C.S.I.a, Michael J. Kerin, M.Ch., F.R.C.S.I.a a Department of Surgery, National Breast Screening Program, Eccles Unit, University College Dublin, 36 Eccles St, Dublin 7, Ireland Department of Radiology, National Breast Cancer Screening Program, Eccles Unit, University College Dublin, Mater Misericordiae University Hospital, 36 Eccles St, Dublin 7, Ireland c Department of Pathology, National Breast Cancer Screening Program, Eccles Unit, University College Dublin, Mater Misericordiae University Hospital, 36 Eccles St, Dublin 7, Ireland
b
Manuscript received April 11, 2006; revised manuscript November 7, 2007
Abstract Background: The role of sentinel lymph node biopsy (SLNB) for ductal carcinoma in situ (DCIS) is poorly defined. However, up to 20% of patients with DCIS will have invasive carcinoma; these patients require staging for axillary metastasis. The aim of this study was to identify patients with a core biopsy diagnosis of DCIS who may benefit from SLNB. Methods: In a prospective study, we performed SLNB on patients with a preoperative diagnosis of ⬎2.5 cm of high-grade DCIS or DCIS when mastectomy was indicated. Results: Sixty-two patients underwent surgery for high-grade DCIS, and 35 of these patients underwent SLNB. Postsurgical excision histology revealed invasive disease in 20 patients, 19 of whom had undergone SLNB. Before the adoption of SLNB in selected DCIS patients, all 20 with occult invasive disease would have required second surgery axillary staging (P ⬍ .01, chi-square test). Conclusions: SLNB should not be performed routinely for all patients with an initial diagnosis of DCIS. However, selective lymphadenectomy may be a useful clinical adjuvant in selected high-risk DCIS patients. © 2007 Excerpta Medica Inc. All rights reserved. Keywords: Ductal carcinoma in situ; Sentinel; Lymph node; Biopsy
Breast cancer screening programs using mammography have greatly increased the detection of ductal carcinoma in situ (DCIS) [1–10]. This disease is characterized by the proliferation of neoplastic ductal epithelial cells that are confined to the basement membrane of mammary ducts [11,12]. DCIS now accounts for greater than 10% of all newly diagnosed breast malignancies and approximately 20% of breast malignancies detected mammographically [4 – 8]. The status of the axillary lymph nodes is the most powerful prognostic indicator of invasive breast cancer [13–18]. The value of lymph node evaluation in the management of DCIS has been much debated; DCIS is a noninvasive disease, and lymphatic metastasis should not occur. Routine * Corresponding author. Tel.: ⫹353-1-882-6200; fax: ⫹353-1-8826225. E-mail address: [email protected]
axillary dissection, in this low-risk group, would be associated with an unacceptably high level of morbidity. The advent of mammographic breast screening with stereotactic-/ultrasound-guided core biopsy provides for preoperative diagnosis, and quality-control criteria in screening programs demand a low rate of open biopsy. However, over 20% of patients with a preoperative diagnosis of DCIS will be upstaged to invasive disease on the excised specimen [4 –12]. This poses a significant problem regarding surgical management because lymphatic staging is the standard of care for breast carcinoma. If not performed at the initial procedure, a second operation is required. The development of sentinel lymph node biopsy (SLNB) has signalled a paradigm shift in surgery of the axilla for breast cancer management [19 –21]. SLNB is an attractive option when considering DCIS; patients at high risk may be accurately staged while avoiding the morbidity
0002-9610/07/$ – see front matter © 2007 Excerpta Medica Inc. All rights reserved. doi:10.1016/j.amjsurg.2006.11.027
C.J. Moran et al. / The American Journal of Surgery 194 (2007) 172–175
and the necessity of a second surgery for those DCIS patients who are found to have invasive disease on final histology. Risk factors associated with invasive disease included large tumors, high-grade tumors, tumors with comedo-type necrosis, and the presence of a palpable mass or mass that is appreciated by imaging studies [22–26]. Until predictors of invasive cancer are clearly identified, the role of SLNB in this group will remain undefined. This study attempts to identify criteria that warrant SLNB after an initial core biopsy diagnosis of DCIS. Methods After ethical committee approval, a prospective analysis of 24,426 patients presenting to a screening unit between January 2002 and December 2003 inclusive was performed. The screening program is consultant delivered and conducted in a female population between the ages of 50 and 65 years, with 2-view mammography at 2-year intervals. Preoperative tissue diagnosis was performed by using stereotactic (mammography based) core biopsy. Core-needle biopsies were performed with either an 11- or 14-G mammatome device, with multiple samples taken from the index lesion until there is radiologic evidence of accurate sampling. SLNB was performed on patients with a preoperative diagnosis of ⬎2.5 cm of high-grade DCIS or in those in whom a mastectomy was indicated (ie, multifocal disease or large-volume disease in a small breast). Written informed consent was obtained from all patients, and the procedure was approved by the institutional ethical review committee. Intraoperative lymphatic mapping of the sentinel node was achieved by using both isosulfan blue dye and a radioactive colloid. The radioactive colloid was injected peritumorally under preoperative radiologic guidance, whereas blue dye was injected into the subareolar dermis intraoperatively. The sentinel node complex was then identified intraoperatively as blue and with radioactive counts greater than 10⫻ the background as assessed by a handheld gamma probe. SLNB was performed through a 2- to 3-cm separate axillary incision. The excised breast specimen and the sentinel node were subjected to serial sectioning and routine hematoxylin-eosin staining in 3 sections/3 levels and 2-mm intervals. The histopathological diagnosis and classification of DCIS was performed in concordance with standard criteria. Immunohistochemistry was not used as part of the current series. Statistical analysis was performed by using the chisquare significance testing. P values ⱕ.05 were considered statistically significant. The SPSS 11.5 software package (SPSS Inc, Chicago, IL) was used for statistical analysis. Results In the 24,426 patients screened as part of the program, 249 screen-detected breast malignancies were diagnosed. The median age of patients was 57 (range, 50 – 65 years), and the median mammographic size was 2.5 cm (range, 0.2–11.5 cm). All patients who underwent surgery at our center had negative surgical margins. The median size of DCIS on final pathological analysis was 4.1 cm (2.5 cm-
173
11.5 cm) in the SLNB group and 2 cm (1 cm to 5.6 cm) in patients not receiving SLNB (P ⬍ .05). Sixty-two had a core biopsy diagnosis of pure DCIS. The initial diagnosis of DCIS was made by percutaneous needle biopsy in all patients; excisional biopsy was not used. On the final specimen histology, 32% (20/62) of patients were shown to have invasive cancer in addition to DCIS. Of the 62 patients with a core biopsy diagnosis of DCIS, 35 of these had SLNB conducted at the time of their initial surgery as a result of meeting the previously defined criteria. Mastectomy was performed in 11 patients and wide local excision in 24. SLNB had been conducted in 95% (19/20) of patients identified with invasive disease on final histology and showed lymphatic metastasis in 3. Of these 3 patients, 2 had micrometastases and 1 had macrometastasis detected in 1 sentinel lymph node (SLN) detected by hematoxylin and eosin staining; no other non-SLN showed metastasis in these patients. Therefore, 3 of 35 patients undergoing SLNB had N1 disease (8.6%) by standard hematoxylin and eosin staining. Invasive carcinoma was identified in 11 of the 24 patients having wide local excision and 8 of the 11 patients having mastectomy. T classification included 17 T1 (10 T1a, 5 T1b, and 2 T1c) and 3 T2 carcinomas. One patient (1/20, 5%) required a second surgery because SLNB was not performed at the initial operation; before the adoption of SLNB in selected DCIS patients, all 20 with occult invasive disease would have required second-surgery axillary staging (P ⬍ .01, chi-square test). Of the 27 patients who did not have SLNB, because this group was outside the criteria, all had wide local excision. Sixteen patients underwent an unnecessary SLNB (16/62, 26%). An audit of these patients indicates that no patient suffered morbidity because of SLNB at a median follow-up of 18 months. Comments DCIS represents a spectrum of disease that may progress to invasive carcinoma, although the incidence of metastases in patients with an initial diagnosis of DCIS is considered to be low. Occult invasion does occur, and, without lymphatic analysis, undertreatment is possible. In our study, we found that 32% of patients with an initial core biopsy diagnosis of DCIS had invasive disease on final surgical excision pathological review. This is slightly higher than that reported by other series [7,11,26 –33]. The finding that some patients diagnosed with DCIS by core-needle biopsy are at risk of harboring invasive disease is a result of the documented problem of histologic underestimation of invasive disease by such percutaneous methods versus excisional biopsy. The majority of core-needle biopsies performed in our series used an 11-G mammatome device because part of our quality-assurance ultrasound is also used to identify any mass lesion and cores are imaged for the presence of calcifications. Our criteria indicated SLNB for patients with ⬎2.5 cm of DCIS or if mastectomy was required. As a result, SLNB was conducted in 95% (19/20) patients found to have invasive disease; 1 patient required a second operation for axillary staging. The findings that larger tumor size and high-
174
C.J. Moran et al. / The American Journal of Surgery 194 (2007) 172–175
grade tumors were predictors of invasive cancer are in agreement with the published literature [34 –38]. In our study, the presence of a clinically palpable mass or the presence of comedonecrosis were not used as indications for SLNB. It has previously been suggested that these may be predictors of invasion. Of the 19 patients who underwent SLNB at the initial procedure, 3 patients had a positive node on standard pathological staining. All 3 received systemic therapy and underwent completion lymphadenectomy that did not show any additional axillary lymph node metastases. The relevance of occult immunohistochemical metastases is doubted, and, for this reason, we have only identified positive SLNB as those with hematoxylin and eosin– detected lymphatic macrometastasis [39 – 42]. We consider that immunohistological evaluation of SLNs is still investigational. Our study had some limitations. First, potential limitations are inherent to any single-institutional, albeit prospective, study. Notwithstanding, the results of this study can be valuable to other institutions with respect to their own recommendations on the use of SLNB in patients with an initial diagnosis of DCIS. The criteria used may provide a basis for the clear identification of predictors of invasion in patients with core biopsy DCIS. Second, the patients in our study have had a relatively short follow-up period. Axillary sampling is recommended in patients identified as having invasive breast carcinoma [43– 48]. Unwarranted axillary clearance is associated with unacceptable morbidity [49]. The use of these criteria to identify high-risk DCIS patients has clearly been fruitful. It has allowed us to identify patients at an increased risk of invasive disease and then offer these patients SLNB. Screening programs mandate maximal staging information while minimizing intervention; the reduction of unnecessary costs and patient stress is also important. SLNB could still be performed as a second surgery for patients without this selection; these patients would then require a second anesthesia with SLNB and even a third anesthesia with axillary clearance if SLNB were positive. We believe that SLNB in a selected cohort of screen-detected DCIS patients reduces morbidity and may therefore improve patient care. References [1] Lagios MD. Duct carcinoma in situ: biological implications for clinical practice Semin Oncol 1996;1(suppl 2):6 –11. [2] Silverstein MJ. Ductal carcinoma in situ of the breast: a surgeon’s disease. Ann Surg Oncol 1999;6:802–10. [3] Leonard GD, Swain SM. Ductal carcinoma in situ, complexities and challenges. J Natl Cancer Inst 2004;96:906 –20. [4] Greenlee RT, Murray T, Bolden S, Wingo PA. Cancer statistics, 2000. CA Cancer J Clin 2000;50:7–33. [5] Holland R, Peterse JL, Millis RR, et al. Ductal carcinoma in situ: a proposal for a new classification. Semin Diagn Pathol 1994;11: 167– 80. [6] Noguchi M. Current controversies concerning sentinel lymph node biopsy for breast cancer. Breast Cancer Res Treat 2004;84:261–71. [7] Cox CE, Nguyen K, Gray RJ, et al. Importance of lymphatic mapping in ductal carcinoma in situ (DCIS): why map DCIS? Am Surg 2001;67:513– 8. [8] Silverstein MJ. Ductal carcinoma of the breast. BMJ 1998;317:734 –9. [9] Kelly TA, Kim JA, Patrick R, et al. Axillary lymph node metastases in patients with a final diagnosis of ductal carcinoma in situ. Am J Surg 2003;186:368 –70. [10] Pendas S, Dauway E, Giuliano R, et al. Sentinel node biopsy in ductal carcinoma in situ patients. Ann Surg Oncol 2000;7:15–20.
[11] Cserni G. Sentinel lymph node biopsy as a tool for the staging of ductal carcinoma in situ in patients with breast carcinoma. Surg Today 2002;32:99 –103. [12] Adamovich TL, Simons RM. Ductal carcinoma in situ with microinvasion. Am J Surg 2003;186:112– 6. [13] Cox CE, Pendas S, Cox JM, et al. Guidelines for sentinel node biopsy and lymphatic mapping of patients with breast cancer. Ann Surg 1998;227:645–53. [14] Turner RR, Ollila DW, Krasne DL, Giuliano AE. Histopathological validation of the sentinel lymph node hypothesis for breast carcinoma. Ann Surg 1997;226:271– 6. [15] Albertini JJ, Lyman GH, Cox C, et al. Lymphatic mapping and sentinel node biopsy in the patient with breast cancer. JAMA 1996; 276:1818 –22. [16] Giuliano AE, Dale PS, Turner RR, et al. Improved axillary staging of breast cancer with sentinel lymphadenectomy. Ann Surg 1995;222: 394 –9. [17] Veronesi U, Paganelli G, Galimberti V, et al. Sentinel node biopsy to avoid axillary dissection in breast cancer with clinically negative lymph nodes. Lancet 1997;349:1864 –7. [18] Giuliano AE, Jones RC, Brennan M, Statman RR. Sentinel lymphadenectomy in breast cancer. J Clin Oncol 1997;15:2345–50. [19] Kell MR, Kerin MJ. Sentinel lymph node biopsy. BMJ 2004;328: 1330 –1. [20] Lagios MD, Silverstein MJ. Sentinel node biopsy for patients with DCIS: a dangerous and unwarranted direction. Ann Surg Oncol 2001; 8:275–7. [21] Silverstein MJ, Gierson ED, Colburn WJ, et al. Axillary lymphadenectomy for intraductal carcinoma of the breast. Surg Gynecol Obstet 1991;172:211– 4. [22] Silverstein MJ, Barth A, Poller DN, et al: Ten-year results comparing mastectomy to excision and radiation therapy for ductal carcinoma of the breast. Eur J Cancer 1995;31:1425–7. [23] Silverstein MJ, Barth A, Poller DN, et al. A prognostic Index for ductal carcinoma of the breast. Lancet 1995;345:1154 –7. [24] Silverstein MJ, Lagios MD, Craig PH, et al. A prognostic index for ductal carcinoma in situ of the breast. Cancer 1996;77:2267–74. [25] Tabar L, Chen HH, Duffy SW. A novel method for prediction of long term outcome of women with T1a, T1b and 10-14mm of invasive breast cancer: a prospective study. Lancet 2000;355:429 –33. [26] Giuliano AE, Kirgan DM, Guenther JM, Morton DL. Lymphatic mapping and sentinel lymphadenectomy for breast cancer. Ann Surg 1994;220:391– 8. [27] Guenther JM, Krishnamoorthy M, Tan LR. Sentinel lymphadenectomy for breast cancer in a community managed care setting. Cancer J Sci Am 1997;3:336 – 40. [28] Offidile R, Hoh C, Barsky SH, et al. Minimally invasive breast carcinoma staging using lymphatic mapping with radiolabelled dextran. Cancer 1998;82:1704 – 8. [29] Reuhl T, Kaisers H, Markwardt J, Haensch W, Hohenberger P, Schlag PM. Axillary node removal in clinical node-negative breast carcinoma. Can its indication be individualized by “sentinel node” detection? Dtsch Med Wochenschr 1998;123:583–7. [30] Peley G, Sinkovics I, Liszkay G, et al. The role of intra-operative gamma-probe guided sentinel lymph node biopsy in the treatment of malignant melanoma and breast cancer (Hungarian). Orv Hetil 1999; 140:2331– 8. [31] Imoto S, Hasebe T. Initial experience with sentinel node biopsy in breast cancer at the National Cancer Centre Hospital East. Jpn J Clin Oncol 1999;29:11–5. [32] Klauber de More N, Tan LK, Liberman L, et al. Sentinel lymph node biopsy—is it indicated in patients with DCIS and patients with microinvasion? Ann Surg Oncol 2000;7:636 – 42. [33] Intra M, Veronesi P, Mazzarol G, et al. Axillary sentinel lymph node biopsy in patients with pure ductal carcinoma in situ of the breast. Arch Surg 2003;138:309 –13. [34] Lee CH, Carter D, Philpotts SE, et al. Ductal carcinoma in situ diagnosed with stereotactic core needle biopsy: can invasion be predicted? Radiology 2000;217:466 –70. [35] Schwartz GF, Patchefsky AS, Finklestein SD, et al. Nonpalpable in situ ductal carcinoma of the breast. Predictors of multicentricity and microinvasion and implications for treatment. Arch Surg 1989;124: 29 –32.
C.J. Moran et al. / The American Journal of Surgery 194 (2007) 172–175 [36] Chung MA, Wazer D, Cady B. Contemporary management of breast cancer. Obstet Gynecol Clin North Am 2002;29:173– 88. [37] Lara JF, Young SM, Velilla RE, et al. The relevance of occult axillary micrometastasis in ductal carcinoma in situ: a clinicopathologic study with long-term follow-up. Cancer 2003;98:2105–13. [38] Jakub JW, Cox CE, Pippas AW, Gardner M, Pendas S, Reintgen DS. Controversial topics in breast lymphatic mapping. Semin Oncol 2004; 31:324 –32. [39] Cody HS, Klauber DeMore N, Borgen PI, et al. Is it really duct carinoma in situ? Ann Surg Oncol 2001;8:617–9. [40] Dowlatshahi K, Fan M, Snider HC. Lymph node micrometastases from breast carcinoma: reviewing the dilemma. Cancer 1997;80: 1188 –97. [41] Cote RJ, Peterson HF, Chaiwun B. Role of immunohistochemical detection of lymph node metastases in management of breast cancer. International Breast Cancer Study Group. Lancet 1999; 354:896 –900. [42] Diel IJ, Kaufmann M, Costa SD. Micrometastic breast cancer cells in bone marrow at primary surgery: prognostic value in comparison with nodal status. J Natl Cancer Inst 1996;88:1652– 64.
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[43] Braun S, Pantel K, Muller P. Cytokeratin-positive cells in the bone marrow and survival of patients with stage I, II or III breast cancer. N Engl J Med 2000;342:525–33. [44] Mullenix PS, Cuadrado DG, Steele SR, et al. Secondary operations are frequently required to complete the surgical phase of therapy in the era of breast conservation and sentinel lymph node biopsy. Am J Surg 2004;187:643– 6. [45] Arnaud S. Patients and surgeons perspectives on axillary surgery for breast cancer. Eur J Surg Oncol 2004;30:735– 43. [46] Gemignani ML, Cody HS, Fey JV, et al. Impact of sentinel lymph node mapping on related charges in patients with early-stage breast cancer. Ann Surg Oncol 2000;7:575– 80. [47] Rutgers EJ. Sentinel node procedure in breast carcinoma: a valid tool to omit unnecessary axillary treatment or even more? Eur J Cancer 2004;40:182– 6. [48] Fuhrman GM. Sentinel lymph node mapping and biopsy for ductal carcinoma in situ and other controversial indications. Am Surg 2004; 70:403– 6. [49] Farkas EA, Stolier AJ, Teng SC, et al. An argument against routine sentinel node mapping for DCIS. Am Surg 2004;70:13–7.
Clinical surgery–International
Role of sentinel lymph node biopsy in high-risk ductal carcinoma in situ patients Cathal J. Moran, F.R.C.S.I.a, Malcolm R. Kell, M.D., F.R.C.S.I.a,*, Fidelma L. Flanagan, M.D., F.R.C.R.b, Maria Kennedy, M.R.C.Pathc, Thomas F. Gorey, M.Ch., F.R.C.S.I.a, Michael J. Kerin, M.Ch., F.R.C.S.I.a a Department of Surgery, National Breast Screening Program, Eccles Unit, University College Dublin, 36 Eccles St, Dublin 7, Ireland Department of Radiology, National Breast Cancer Screening Program, Eccles Unit, University College Dublin, Mater Misericordiae University Hospital, 36 Eccles St, Dublin 7, Ireland c Department of Pathology, National Breast Cancer Screening Program, Eccles Unit, University College Dublin, Mater Misericordiae University Hospital, 36 Eccles St, Dublin 7, Ireland
b
Manuscript received April 11, 2006; revised manuscript November 7, 2007
Abstract Background: The role of sentinel lymph node biopsy (SLNB) for ductal carcinoma in situ (DCIS) is poorly defined. However, up to 20% of patients with DCIS will have invasive carcinoma; these patients require staging for axillary metastasis. The aim of this study was to identify patients with a core biopsy diagnosis of DCIS who may benefit from SLNB. Methods: In a prospective study, we performed SLNB on patients with a preoperative diagnosis of ⬎2.5 cm of high-grade DCIS or DCIS when mastectomy was indicated. Results: Sixty-two patients underwent surgery for high-grade DCIS, and 35 of these patients underwent SLNB. Postsurgical excision histology revealed invasive disease in 20 patients, 19 of whom had undergone SLNB. Before the adoption of SLNB in selected DCIS patients, all 20 with occult invasive disease would have required second surgery axillary staging (P ⬍ .01, chi-square test). Conclusions: SLNB should not be performed routinely for all patients with an initial diagnosis of DCIS. However, selective lymphadenectomy may be a useful clinical adjuvant in selected high-risk DCIS patients. © 2007 Excerpta Medica Inc. All rights reserved. Keywords: Ductal carcinoma in situ; Sentinel; Lymph node; Biopsy
Breast cancer screening programs using mammography have greatly increased the detection of ductal carcinoma in situ (DCIS) [1–10]. This disease is characterized by the proliferation of neoplastic ductal epithelial cells that are confined to the basement membrane of mammary ducts [11,12]. DCIS now accounts for greater than 10% of all newly diagnosed breast malignancies and approximately 20% of breast malignancies detected mammographically [4 – 8]. The status of the axillary lymph nodes is the most powerful prognostic indicator of invasive breast cancer [13–18]. The value of lymph node evaluation in the management of DCIS has been much debated; DCIS is a noninvasive disease, and lymphatic metastasis should not occur. Routine * Corresponding author. Tel.: ⫹353-1-882-6200; fax: ⫹353-1-8826225. E-mail address: [email protected]
axillary dissection, in this low-risk group, would be associated with an unacceptably high level of morbidity. The advent of mammographic breast screening with stereotactic-/ultrasound-guided core biopsy provides for preoperative diagnosis, and quality-control criteria in screening programs demand a low rate of open biopsy. However, over 20% of patients with a preoperative diagnosis of DCIS will be upstaged to invasive disease on the excised specimen [4 –12]. This poses a significant problem regarding surgical management because lymphatic staging is the standard of care for breast carcinoma. If not performed at the initial procedure, a second operation is required. The development of sentinel lymph node biopsy (SLNB) has signalled a paradigm shift in surgery of the axilla for breast cancer management [19 –21]. SLNB is an attractive option when considering DCIS; patients at high risk may be accurately staged while avoiding the morbidity
0002-9610/07/$ – see front matter © 2007 Excerpta Medica Inc. All rights reserved. doi:10.1016/j.amjsurg.2006.11.027
C.J. Moran et al. / The American Journal of Surgery 194 (2007) 172–175
and the necessity of a second surgery for those DCIS patients who are found to have invasive disease on final histology. Risk factors associated with invasive disease included large tumors, high-grade tumors, tumors with comedo-type necrosis, and the presence of a palpable mass or mass that is appreciated by imaging studies [22–26]. Until predictors of invasive cancer are clearly identified, the role of SLNB in this group will remain undefined. This study attempts to identify criteria that warrant SLNB after an initial core biopsy diagnosis of DCIS. Methods After ethical committee approval, a prospective analysis of 24,426 patients presenting to a screening unit between January 2002 and December 2003 inclusive was performed. The screening program is consultant delivered and conducted in a female population between the ages of 50 and 65 years, with 2-view mammography at 2-year intervals. Preoperative tissue diagnosis was performed by using stereotactic (mammography based) core biopsy. Core-needle biopsies were performed with either an 11- or 14-G mammatome device, with multiple samples taken from the index lesion until there is radiologic evidence of accurate sampling. SLNB was performed on patients with a preoperative diagnosis of ⬎2.5 cm of high-grade DCIS or in those in whom a mastectomy was indicated (ie, multifocal disease or large-volume disease in a small breast). Written informed consent was obtained from all patients, and the procedure was approved by the institutional ethical review committee. Intraoperative lymphatic mapping of the sentinel node was achieved by using both isosulfan blue dye and a radioactive colloid. The radioactive colloid was injected peritumorally under preoperative radiologic guidance, whereas blue dye was injected into the subareolar dermis intraoperatively. The sentinel node complex was then identified intraoperatively as blue and with radioactive counts greater than 10⫻ the background as assessed by a handheld gamma probe. SLNB was performed through a 2- to 3-cm separate axillary incision. The excised breast specimen and the sentinel node were subjected to serial sectioning and routine hematoxylin-eosin staining in 3 sections/3 levels and 2-mm intervals. The histopathological diagnosis and classification of DCIS was performed in concordance with standard criteria. Immunohistochemistry was not used as part of the current series. Statistical analysis was performed by using the chisquare significance testing. P values ⱕ.05 were considered statistically significant. The SPSS 11.5 software package (SPSS Inc, Chicago, IL) was used for statistical analysis. Results In the 24,426 patients screened as part of the program, 249 screen-detected breast malignancies were diagnosed. The median age of patients was 57 (range, 50 – 65 years), and the median mammographic size was 2.5 cm (range, 0.2–11.5 cm). All patients who underwent surgery at our center had negative surgical margins. The median size of DCIS on final pathological analysis was 4.1 cm (2.5 cm-
173
11.5 cm) in the SLNB group and 2 cm (1 cm to 5.6 cm) in patients not receiving SLNB (P ⬍ .05). Sixty-two had a core biopsy diagnosis of pure DCIS. The initial diagnosis of DCIS was made by percutaneous needle biopsy in all patients; excisional biopsy was not used. On the final specimen histology, 32% (20/62) of patients were shown to have invasive cancer in addition to DCIS. Of the 62 patients with a core biopsy diagnosis of DCIS, 35 of these had SLNB conducted at the time of their initial surgery as a result of meeting the previously defined criteria. Mastectomy was performed in 11 patients and wide local excision in 24. SLNB had been conducted in 95% (19/20) of patients identified with invasive disease on final histology and showed lymphatic metastasis in 3. Of these 3 patients, 2 had micrometastases and 1 had macrometastasis detected in 1 sentinel lymph node (SLN) detected by hematoxylin and eosin staining; no other non-SLN showed metastasis in these patients. Therefore, 3 of 35 patients undergoing SLNB had N1 disease (8.6%) by standard hematoxylin and eosin staining. Invasive carcinoma was identified in 11 of the 24 patients having wide local excision and 8 of the 11 patients having mastectomy. T classification included 17 T1 (10 T1a, 5 T1b, and 2 T1c) and 3 T2 carcinomas. One patient (1/20, 5%) required a second surgery because SLNB was not performed at the initial operation; before the adoption of SLNB in selected DCIS patients, all 20 with occult invasive disease would have required second-surgery axillary staging (P ⬍ .01, chi-square test). Of the 27 patients who did not have SLNB, because this group was outside the criteria, all had wide local excision. Sixteen patients underwent an unnecessary SLNB (16/62, 26%). An audit of these patients indicates that no patient suffered morbidity because of SLNB at a median follow-up of 18 months. Comments DCIS represents a spectrum of disease that may progress to invasive carcinoma, although the incidence of metastases in patients with an initial diagnosis of DCIS is considered to be low. Occult invasion does occur, and, without lymphatic analysis, undertreatment is possible. In our study, we found that 32% of patients with an initial core biopsy diagnosis of DCIS had invasive disease on final surgical excision pathological review. This is slightly higher than that reported by other series [7,11,26 –33]. The finding that some patients diagnosed with DCIS by core-needle biopsy are at risk of harboring invasive disease is a result of the documented problem of histologic underestimation of invasive disease by such percutaneous methods versus excisional biopsy. The majority of core-needle biopsies performed in our series used an 11-G mammatome device because part of our quality-assurance ultrasound is also used to identify any mass lesion and cores are imaged for the presence of calcifications. Our criteria indicated SLNB for patients with ⬎2.5 cm of DCIS or if mastectomy was required. As a result, SLNB was conducted in 95% (19/20) patients found to have invasive disease; 1 patient required a second operation for axillary staging. The findings that larger tumor size and high-
174
C.J. Moran et al. / The American Journal of Surgery 194 (2007) 172–175
grade tumors were predictors of invasive cancer are in agreement with the published literature [34 –38]. In our study, the presence of a clinically palpable mass or the presence of comedonecrosis were not used as indications for SLNB. It has previously been suggested that these may be predictors of invasion. Of the 19 patients who underwent SLNB at the initial procedure, 3 patients had a positive node on standard pathological staining. All 3 received systemic therapy and underwent completion lymphadenectomy that did not show any additional axillary lymph node metastases. The relevance of occult immunohistochemical metastases is doubted, and, for this reason, we have only identified positive SLNB as those with hematoxylin and eosin– detected lymphatic macrometastasis [39 – 42]. We consider that immunohistological evaluation of SLNs is still investigational. Our study had some limitations. First, potential limitations are inherent to any single-institutional, albeit prospective, study. Notwithstanding, the results of this study can be valuable to other institutions with respect to their own recommendations on the use of SLNB in patients with an initial diagnosis of DCIS. The criteria used may provide a basis for the clear identification of predictors of invasion in patients with core biopsy DCIS. Second, the patients in our study have had a relatively short follow-up period. Axillary sampling is recommended in patients identified as having invasive breast carcinoma [43– 48]. Unwarranted axillary clearance is associated with unacceptable morbidity [49]. The use of these criteria to identify high-risk DCIS patients has clearly been fruitful. It has allowed us to identify patients at an increased risk of invasive disease and then offer these patients SLNB. Screening programs mandate maximal staging information while minimizing intervention; the reduction of unnecessary costs and patient stress is also important. SLNB could still be performed as a second surgery for patients without this selection; these patients would then require a second anesthesia with SLNB and even a third anesthesia with axillary clearance if SLNB were positive. We believe that SLNB in a selected cohort of screen-detected DCIS patients reduces morbidity and may therefore improve patient care. References [1] Lagios MD. Duct carcinoma in situ: biological implications for clinical practice Semin Oncol 1996;1(suppl 2):6 –11. [2] Silverstein MJ. Ductal carcinoma in situ of the breast: a surgeon’s disease. Ann Surg Oncol 1999;6:802–10. [3] Leonard GD, Swain SM. Ductal carcinoma in situ, complexities and challenges. J Natl Cancer Inst 2004;96:906 –20. [4] Greenlee RT, Murray T, Bolden S, Wingo PA. Cancer statistics, 2000. CA Cancer J Clin 2000;50:7–33. [5] Holland R, Peterse JL, Millis RR, et al. Ductal carcinoma in situ: a proposal for a new classification. Semin Diagn Pathol 1994;11: 167– 80. [6] Noguchi M. Current controversies concerning sentinel lymph node biopsy for breast cancer. Breast Cancer Res Treat 2004;84:261–71. [7] Cox CE, Nguyen K, Gray RJ, et al. Importance of lymphatic mapping in ductal carcinoma in situ (DCIS): why map DCIS? Am Surg 2001;67:513– 8. [8] Silverstein MJ. Ductal carcinoma of the breast. BMJ 1998;317:734 –9. [9] Kelly TA, Kim JA, Patrick R, et al. Axillary lymph node metastases in patients with a final diagnosis of ductal carcinoma in situ. Am J Surg 2003;186:368 –70. [10] Pendas S, Dauway E, Giuliano R, et al. Sentinel node biopsy in ductal carcinoma in situ patients. Ann Surg Oncol 2000;7:15–20.
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