- Email: [email protected]
Do sentinel node micrometastases predict recurrence risk in ductal carcinoma in situ and ductal carcinoma in situ with microinvasion?
The American Journal of Surgery (2008) 196, 566 –568
The American Society of Breast Surgeons
Do sentinel node micrometastases predict recurrence risk in ductal carcinoma in situ and ductal carcinoma in situ with microinvasion? Colleen D. Murphy, M.D.a,*, Julie L. Jones, M.D.b, Sara Hughes Javid, M.D.a, James S. Michaelson, Ph.D.a, Matthew E. Nolan, A.B.a, Stuart R. Lipsitz, Sc.D.c, Michelle C. Specht, M.D.a, Beth-Ann Lesnikoski, M.D.b, Kevin S. Hughes, M.D.a, Michele A. Gadd, M.D.a, Barbara L. Smith, M.D., Ph.D.a a
Division of Surgical Oncology, Massachusetts General Hospital, Boston, MA, USA; bDivision of Surgical Oncology, Brigham and Women’s Hospital, Boston, MA, USA; cDepartments of Medicine and Surgery, Brigham and Women’s Hospital, Boston, MA KEYWORDS: Breast neoplasm; Ductal carcinoma in situ; Ductal carcinoma in situ with microinvasion; Sentinel lymph node biopsy; Sentinel lymph node micrometastases
Abstract BACKGROUND: Because the implications of micrometastases found on sentinel node biopsy (SNB) for ductal carcinoma in situ (DCIS) or ductal carcinoma in situ with microinvasion (DCISM) are largely unknown, we wished to determine if SNB pathology predicted recurrence risk in DCIS/DCISM. METHODS: Retrospective chart review identified patients with DCIS/DCISM who underwent SNB. SNB findings and all local and distant recurrences were determined. RESULTS: A total of 322 patients underwent SNB for DCIS/DCISM. There were 13 local recurrences (4.0%) and 1 (.03%) distant recurrence at a median follow-up of 47.9 months (range 0 to 110.6), 12 in patients with negative SNBs; 1 patient had a positive SNB. There were 4 recurrences after mastectomy and 9 after lumpectomy. In 29 patients with positive SNBs, there was only 1 recurrence (3.4%). CONCLUSIONS: Positive SNBs in patients with DCIS or DCISM are not associated with higher risk of local or distant recurrence. Other features of DCIS and DCISM may be important in predicting recurrence risk. © 2008 Elsevier Inc. All rights reserved.
Sentinel node biopsy (SNB) has been well validated for staging invasive breast cancer with low rates of axillary recurrence.1 Some investigators have recommended routine SNB for ductal carcinoma in situ (DCIS) or ductal carcinoma in situ with microinvasion (DCISM) because 8% to 12% of these patients are found to have nodal metastases on SNB2, and 10% to 20%3 of patients with DCIS are upstaged to invasive disease at definitive surgery. Because there are
little data on the long-term implications of such SNB metastases, and because local recurrence rates for DCIS are higher than for invasive disease, we wished to determine if SNB pathology predicted local recurrence risk in patients with DCIS or DCISM.
* Corresponding author. Tel.: ⫹1-617-724-1074; fax: ⫹1-617-724-1079. E-mail address: [email protected] Manuscript received April 16, 2008; revised manuscript June 4, 2008
Institutional Review Board–approved chart review identified 322 patients with DCIS or DCISM on final pathology who underwent SNB from 1997 to 2003. SNB was per-
0002-9610/$ - see front matter © 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.amjsurg.2008.06.011
Patients and Methods
C.D. Murphy et al. Table 1
567
Recurrences observed in patients with DCIS and DCISM
Treatment Mastectomy Breast conservation a
Do sentinel node micrometastases predict recurrence risk?
SNB status
No. of patients
No. with distant recurrence (%)
No. with local recurrence (%)
Local recurrence (P)
Positive Negative Positive Negative
21 198 8 95
0 4a (2.0) 0 0
0 4 (2.0) 1 (12.5) 8 (8.4)
.99 .53
Three of 4 patients had synchronous contralateral invasive cancer.
formed with mastectomy and selectively with lumpectomy, primarily for large or high-grade DCIS or DCISM on diagnostic biopsy. An SNB was considered positive if tumor cells were identified on immunohistochemical (IHC) or routine hematoxlyn-and-eosin (H&E) staining. All patients had negative margins by our institutional standard (ⱖ2 mm). Recurrences were identified by chart review. Local recurrences were defined as in-breast recurrence after breast conservation, chest wall recurrence after mastectomy, or recurrence within the axilla. All other recurrences were considered distant.
Results Overall, 29 (9.0%) patients had positive SNBs, 18 (5.6%) identified by IHC alone and 11 (3.4%) by H&E. There were 25 patients with isolated tumor cells (pN0(i⫹)), 3 patients with micrometastases (pN1mic), and 1 patient with a macrometastasis (pN1). Positive SNBs were found in 12.1% of DCIS and 3.7% of DCISM patients. Seven positive SNB patients had completion axillary lymph node dissections, and no additional positive nodes were revealed. All patients who underwent breast conservation received radiation, and 2 who underwent mastectomy received chest wall radiation, 1 for a focally positive posterior margin and the other for extensive high-grade DCIS with microinvasion and 2 sentinel nodes positive for isolated tumor cells. Twelve positive SNB patients (41.4%) received adjuvant chemotherapy, and 21 (72.4%) received adjuvant hormonal therapy. At 47.9-month median follow-up (range 0 to 110.6), there were 13 (4.0%) local recurrences, 4 after mastectomy and 9 after lumpectomy (Table 1). There was 1 distant recurrence that occurred 20 months after a local recurrence. Only 1 of 13 local recurrence patients had had a positive SNB. This patient had high-grade DCIS suspicious for microinvasion and an SNB with rare tumor cell clusters by H&E and underwent lumpectomy, SNB, radiation, and adjuvant administration of cyclophosphamide, doxorubicin, and tamoxifen. The recurrence was intermediate-grade DCIS found by mammography 13.4 months after diagnosis of the primary cancer. Overall there were 4 breast cancer–related deaths, 3 in patients with synchronous contralateral invasive breast can-
cer. One death occurred in a patient with a negative SNB and high-grade DCISM treated by mastectomy who developed metastatic disease 20 months after chest wall recurrence.
Comments Historically, survival for patients with DCIS and DCISM treated by breast conservation or mastectomy is 97% to 100%4, with death presumed because of spread of unrecognized or small numbers of invasive tumor cells. In invasive breast cancer, the major role of SNB is to identify patients whose tumor cells have spread beyond the breast, identifying higher risk for systemic disease. It has therefore been suggested that SNB be performed in patients with high-risk DCIS, ie, high risk of occult invasive cancer, including those with microinvasion. Several studies have helped identify subgroups of patients at higher risk for occult invasive disease. Yen et al5 demonstrated that patient age ⱕ55 years, diagnosis by coreneedle biopsy, mammographic DCIS size ⱖ4 cm, and highgrade DCIS were independent predictors of invasive cancer on final pathology, whereas only palpable tumor was predictive of a positive sentinel node. Tan et al6 found that comedonecrosis and diagnosis by core-needle biopsy were independent risk factors for invasion in patients undergoing mastectomy and SNB for DCIS, but they found no risk factors predictive for sentinel node metastases. Although the results of these studies have helped to determine which DCIS patients are appropriate candidates for SNB, few have examined long-term outcomes in patients with sentinel node metastases. Broekhuizen et al7 examined 71 patients with DCIS and 12 with DCIS with ⬍2 mm invasion who had excision of ⱖ5 nodes and found that 11 of 83 patients (13.3%) had positive axillary nodes by IHC or H&E staining. Of positive lymph nodes, 8 contained isolated tumor cells (ITCs), 1 contained micrometastases, and 2 contained macrometastases. At a median follow-up of 102 months, all patients remained free of disease. Moore et al8 found 43 (9.1%) positive sentinel nodes in 470 patients with high-risk DCIS: 36 ITCs, 4 micrometastases, and 3 macrometastases. Of 25 patients who underwent ALND, only 1 was found to have additional positive nodes. No local recurrences were observed, but 1 patient with ITCs devel-
568 oped distant metastases at 27 months. Intra et al9 examined 854 patients with pure DCIS (microinvasion excluded) who had undergone SNB and found 4 with ITCs, 7 with micrometastases, and 5 with macrometastases. Eleven of 16 patients underwent ALND with no additional positive nodes. At a median follow-up of 41 months, there were 2 locoregional recurrences and 1 distant recurrence in patients with positive SNBs. The size of nodal deposits in these patients was not reported. Our series of high-risk DCIS and DCISM patients found positive SNBs in 9%, with the majority being pN0(i⫹). At median follow-up of 47.9 months, there were 13 (4.0%) local recurrences and 1 distant recurrence, all but 1 in sentinel node–negative patients. Combining our data with those of previous studies, there were 88 of 1,246 (7.1%) positive sentinel nodes (including ITCs) with 5 (.04%) recurrences: 3 locoregional and 2 distant. El-Tamer et al10 demonstrated that positive lymph nodes detected by IHC in patients with DCIS did not alter breast cancer recurrence or survival, which is in agreement with our findings. In invasive disease, it is unclear if micrometastases or macrometastases on SNB confer a worse prognosis, and a prospective trial is underway to address this question. In our series of patients with DCIS and DCISM, no recurrences were observed in patients with micrometastases or macrometastases on SNB. However, because these patients had N1 disease, 75% of patients underwent ALND, 50% received adjuvant chemotherapy, and 100% received hormonal therapy. Overall we found a 4% local recurrence rate for DCIS/ DCISM with a .003% DCIS/DCISM–specific mortality rate. Both of these numbers are lower than typically reported recurrence and mortality rates for DCIS/DCISM. However, our study is limited by the small number of patients and shorter median follow-up. In conclusion, we found no prognostic significance of sentinel node metastases with respect to survival or local recurrence for both DCIS and DCISM. Other clinical and pathologic characteristics may be important in predicting risk of recurrent disease in these patients. These data argue against the routine use of SNB in DCIS/DCISM, even when DCIS is diagnosed by stereotactic core biopsy. Although some patients diagnosed with DCIS on core biopsy will be found to have invasion at lumpectomy, many will have only microinvasion that does not require SNB. In addition, many patients with DCIS
The American Journal of Surgery, Vol 196, No 4, October 2008 require re-excision to obtain negative margins, and SNB could be performed at that time if required. We favor SNB as a separate procedure for the small percentage of patents found to have more than microinvasion at lumpectomy rather than up-front SNB for all patients with DCIS on core biopsy. Given the challenge of SNB after mastectomy, we recommend SNB in all patients undergoing mastectomy for DCIS or DCISM. We also consider SNB with lumpectomy for patients with microinvasion on core biopsy and selectively for patients with extensive calcifications and highgrade DCIS on core biopsy.
References 1. Naik AM, Fey J, Gemignani M, et al. The risk of axillary relapse after sentinel lymph node biopsy for breast cancer is comparable with that of axillary lymph node dissection: a follow-up study of 4008 procedures. Ann Surg 2004;240:462– 8. 2. Cox CE, Nguyen K, Gray RJ, et al. Importance of lymphatic mapping in ductal carcinoma in situ (DCIS): why map DCIS? Am Surg 2001; 67:513–9. 3. Dominguez FJ, Golshan M, Black DM, et al. Sentinel node biopsy is important in mastectomy for ductal carcinoma in situ. Ann Surg Oncol 2008;15:268 –73. 4. de Mascarel I, MacGrogan G, Mathoulin-Pelissier S, et al. Breast ductal carcinoma in situ with microinvasion: a definition supported by a long-term study of 1248 serially sectioned ductal carcinomas. Cancer 2002;94:2134 – 42. 5. Yen TW, Hunt KK, Ross MI, et al. Predictors of invasive breast cancer in patients with an initial diagnosis of ductal carcinoma in situ: a guide to selective use of sentinel lymph node biopsy in management of ductal carcinoma in situ. J Am Coll Surg 2005;200:516 –26. 6. Tan JC, McCready DR, Easson AM, et al. Role of sentinel lymph node biopsy in ductal carcinoma-in-situ treated by mastectomy. Ann Surg Oncol 2007;14:638 – 45. 7. Broekhuizen LN, Wijsman JH, Peterse JL, et al. The incidence and significance of micrometastases in lymph nodes of patients with ductal carcinoma in situ and T1a carcinoma of the breast. Eur J Surg Oncol 2006;32:502– 6. 8. Moore KH, Sweeney KJ, Wilson ME, et al. Outcomes for women with ductal carcinoma-in-situ and a positive sentinel node: a multi-institutional audit. Ann Surg Oncol 2007;14:2911–7. 9. Intra M, Rotmensz N, Veronesi P, et al. Sentinel node biopsy is not a standard procedure in ductal carcinoma in situ of the breast: the experience of the European institute of oncology on 854 patients in 10 years. Ann Surg 2008;247:315–9. 10. El-Tamer M, Chun J, Gill M, et al. Incidence and clinical significance of lymph node metastasis detected by cytokeratin immunohistochemical staining in ductal carcinoma in situ. Ann Surg Oncol 2005;12: 254 –9.
The American Society of Breast Surgeons
Do sentinel node micrometastases predict recurrence risk in ductal carcinoma in situ and ductal carcinoma in situ with microinvasion? Colleen D. Murphy, M.D.a,*, Julie L. Jones, M.D.b, Sara Hughes Javid, M.D.a, James S. Michaelson, Ph.D.a, Matthew E. Nolan, A.B.a, Stuart R. Lipsitz, Sc.D.c, Michelle C. Specht, M.D.a, Beth-Ann Lesnikoski, M.D.b, Kevin S. Hughes, M.D.a, Michele A. Gadd, M.D.a, Barbara L. Smith, M.D., Ph.D.a a
Division of Surgical Oncology, Massachusetts General Hospital, Boston, MA, USA; bDivision of Surgical Oncology, Brigham and Women’s Hospital, Boston, MA, USA; cDepartments of Medicine and Surgery, Brigham and Women’s Hospital, Boston, MA KEYWORDS: Breast neoplasm; Ductal carcinoma in situ; Ductal carcinoma in situ with microinvasion; Sentinel lymph node biopsy; Sentinel lymph node micrometastases
Abstract BACKGROUND: Because the implications of micrometastases found on sentinel node biopsy (SNB) for ductal carcinoma in situ (DCIS) or ductal carcinoma in situ with microinvasion (DCISM) are largely unknown, we wished to determine if SNB pathology predicted recurrence risk in DCIS/DCISM. METHODS: Retrospective chart review identified patients with DCIS/DCISM who underwent SNB. SNB findings and all local and distant recurrences were determined. RESULTS: A total of 322 patients underwent SNB for DCIS/DCISM. There were 13 local recurrences (4.0%) and 1 (.03%) distant recurrence at a median follow-up of 47.9 months (range 0 to 110.6), 12 in patients with negative SNBs; 1 patient had a positive SNB. There were 4 recurrences after mastectomy and 9 after lumpectomy. In 29 patients with positive SNBs, there was only 1 recurrence (3.4%). CONCLUSIONS: Positive SNBs in patients with DCIS or DCISM are not associated with higher risk of local or distant recurrence. Other features of DCIS and DCISM may be important in predicting recurrence risk. © 2008 Elsevier Inc. All rights reserved.
Sentinel node biopsy (SNB) has been well validated for staging invasive breast cancer with low rates of axillary recurrence.1 Some investigators have recommended routine SNB for ductal carcinoma in situ (DCIS) or ductal carcinoma in situ with microinvasion (DCISM) because 8% to 12% of these patients are found to have nodal metastases on SNB2, and 10% to 20%3 of patients with DCIS are upstaged to invasive disease at definitive surgery. Because there are
little data on the long-term implications of such SNB metastases, and because local recurrence rates for DCIS are higher than for invasive disease, we wished to determine if SNB pathology predicted local recurrence risk in patients with DCIS or DCISM.
* Corresponding author. Tel.: ⫹1-617-724-1074; fax: ⫹1-617-724-1079. E-mail address: [email protected] Manuscript received April 16, 2008; revised manuscript June 4, 2008
Institutional Review Board–approved chart review identified 322 patients with DCIS or DCISM on final pathology who underwent SNB from 1997 to 2003. SNB was per-
0002-9610/$ - see front matter © 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.amjsurg.2008.06.011
Patients and Methods
C.D. Murphy et al. Table 1
567
Recurrences observed in patients with DCIS and DCISM
Treatment Mastectomy Breast conservation a
Do sentinel node micrometastases predict recurrence risk?
SNB status
No. of patients
No. with distant recurrence (%)
No. with local recurrence (%)
Local recurrence (P)
Positive Negative Positive Negative
21 198 8 95
0 4a (2.0) 0 0
0 4 (2.0) 1 (12.5) 8 (8.4)
.99 .53
Three of 4 patients had synchronous contralateral invasive cancer.
formed with mastectomy and selectively with lumpectomy, primarily for large or high-grade DCIS or DCISM on diagnostic biopsy. An SNB was considered positive if tumor cells were identified on immunohistochemical (IHC) or routine hematoxlyn-and-eosin (H&E) staining. All patients had negative margins by our institutional standard (ⱖ2 mm). Recurrences were identified by chart review. Local recurrences were defined as in-breast recurrence after breast conservation, chest wall recurrence after mastectomy, or recurrence within the axilla. All other recurrences were considered distant.
Results Overall, 29 (9.0%) patients had positive SNBs, 18 (5.6%) identified by IHC alone and 11 (3.4%) by H&E. There were 25 patients with isolated tumor cells (pN0(i⫹)), 3 patients with micrometastases (pN1mic), and 1 patient with a macrometastasis (pN1). Positive SNBs were found in 12.1% of DCIS and 3.7% of DCISM patients. Seven positive SNB patients had completion axillary lymph node dissections, and no additional positive nodes were revealed. All patients who underwent breast conservation received radiation, and 2 who underwent mastectomy received chest wall radiation, 1 for a focally positive posterior margin and the other for extensive high-grade DCIS with microinvasion and 2 sentinel nodes positive for isolated tumor cells. Twelve positive SNB patients (41.4%) received adjuvant chemotherapy, and 21 (72.4%) received adjuvant hormonal therapy. At 47.9-month median follow-up (range 0 to 110.6), there were 13 (4.0%) local recurrences, 4 after mastectomy and 9 after lumpectomy (Table 1). There was 1 distant recurrence that occurred 20 months after a local recurrence. Only 1 of 13 local recurrence patients had had a positive SNB. This patient had high-grade DCIS suspicious for microinvasion and an SNB with rare tumor cell clusters by H&E and underwent lumpectomy, SNB, radiation, and adjuvant administration of cyclophosphamide, doxorubicin, and tamoxifen. The recurrence was intermediate-grade DCIS found by mammography 13.4 months after diagnosis of the primary cancer. Overall there were 4 breast cancer–related deaths, 3 in patients with synchronous contralateral invasive breast can-
cer. One death occurred in a patient with a negative SNB and high-grade DCISM treated by mastectomy who developed metastatic disease 20 months after chest wall recurrence.
Comments Historically, survival for patients with DCIS and DCISM treated by breast conservation or mastectomy is 97% to 100%4, with death presumed because of spread of unrecognized or small numbers of invasive tumor cells. In invasive breast cancer, the major role of SNB is to identify patients whose tumor cells have spread beyond the breast, identifying higher risk for systemic disease. It has therefore been suggested that SNB be performed in patients with high-risk DCIS, ie, high risk of occult invasive cancer, including those with microinvasion. Several studies have helped identify subgroups of patients at higher risk for occult invasive disease. Yen et al5 demonstrated that patient age ⱕ55 years, diagnosis by coreneedle biopsy, mammographic DCIS size ⱖ4 cm, and highgrade DCIS were independent predictors of invasive cancer on final pathology, whereas only palpable tumor was predictive of a positive sentinel node. Tan et al6 found that comedonecrosis and diagnosis by core-needle biopsy were independent risk factors for invasion in patients undergoing mastectomy and SNB for DCIS, but they found no risk factors predictive for sentinel node metastases. Although the results of these studies have helped to determine which DCIS patients are appropriate candidates for SNB, few have examined long-term outcomes in patients with sentinel node metastases. Broekhuizen et al7 examined 71 patients with DCIS and 12 with DCIS with ⬍2 mm invasion who had excision of ⱖ5 nodes and found that 11 of 83 patients (13.3%) had positive axillary nodes by IHC or H&E staining. Of positive lymph nodes, 8 contained isolated tumor cells (ITCs), 1 contained micrometastases, and 2 contained macrometastases. At a median follow-up of 102 months, all patients remained free of disease. Moore et al8 found 43 (9.1%) positive sentinel nodes in 470 patients with high-risk DCIS: 36 ITCs, 4 micrometastases, and 3 macrometastases. Of 25 patients who underwent ALND, only 1 was found to have additional positive nodes. No local recurrences were observed, but 1 patient with ITCs devel-
568 oped distant metastases at 27 months. Intra et al9 examined 854 patients with pure DCIS (microinvasion excluded) who had undergone SNB and found 4 with ITCs, 7 with micrometastases, and 5 with macrometastases. Eleven of 16 patients underwent ALND with no additional positive nodes. At a median follow-up of 41 months, there were 2 locoregional recurrences and 1 distant recurrence in patients with positive SNBs. The size of nodal deposits in these patients was not reported. Our series of high-risk DCIS and DCISM patients found positive SNBs in 9%, with the majority being pN0(i⫹). At median follow-up of 47.9 months, there were 13 (4.0%) local recurrences and 1 distant recurrence, all but 1 in sentinel node–negative patients. Combining our data with those of previous studies, there were 88 of 1,246 (7.1%) positive sentinel nodes (including ITCs) with 5 (.04%) recurrences: 3 locoregional and 2 distant. El-Tamer et al10 demonstrated that positive lymph nodes detected by IHC in patients with DCIS did not alter breast cancer recurrence or survival, which is in agreement with our findings. In invasive disease, it is unclear if micrometastases or macrometastases on SNB confer a worse prognosis, and a prospective trial is underway to address this question. In our series of patients with DCIS and DCISM, no recurrences were observed in patients with micrometastases or macrometastases on SNB. However, because these patients had N1 disease, 75% of patients underwent ALND, 50% received adjuvant chemotherapy, and 100% received hormonal therapy. Overall we found a 4% local recurrence rate for DCIS/ DCISM with a .003% DCIS/DCISM–specific mortality rate. Both of these numbers are lower than typically reported recurrence and mortality rates for DCIS/DCISM. However, our study is limited by the small number of patients and shorter median follow-up. In conclusion, we found no prognostic significance of sentinel node metastases with respect to survival or local recurrence for both DCIS and DCISM. Other clinical and pathologic characteristics may be important in predicting risk of recurrent disease in these patients. These data argue against the routine use of SNB in DCIS/DCISM, even when DCIS is diagnosed by stereotactic core biopsy. Although some patients diagnosed with DCIS on core biopsy will be found to have invasion at lumpectomy, many will have only microinvasion that does not require SNB. In addition, many patients with DCIS
The American Journal of Surgery, Vol 196, No 4, October 2008 require re-excision to obtain negative margins, and SNB could be performed at that time if required. We favor SNB as a separate procedure for the small percentage of patents found to have more than microinvasion at lumpectomy rather than up-front SNB for all patients with DCIS on core biopsy. Given the challenge of SNB after mastectomy, we recommend SNB in all patients undergoing mastectomy for DCIS or DCISM. We also consider SNB with lumpectomy for patients with microinvasion on core biopsy and selectively for patients with extensive calcifications and highgrade DCIS on core biopsy.
References 1. Naik AM, Fey J, Gemignani M, et al. The risk of axillary relapse after sentinel lymph node biopsy for breast cancer is comparable with that of axillary lymph node dissection: a follow-up study of 4008 procedures. Ann Surg 2004;240:462– 8. 2. Cox CE, Nguyen K, Gray RJ, et al. Importance of lymphatic mapping in ductal carcinoma in situ (DCIS): why map DCIS? Am Surg 2001; 67:513–9. 3. Dominguez FJ, Golshan M, Black DM, et al. Sentinel node biopsy is important in mastectomy for ductal carcinoma in situ. Ann Surg Oncol 2008;15:268 –73. 4. de Mascarel I, MacGrogan G, Mathoulin-Pelissier S, et al. Breast ductal carcinoma in situ with microinvasion: a definition supported by a long-term study of 1248 serially sectioned ductal carcinomas. Cancer 2002;94:2134 – 42. 5. Yen TW, Hunt KK, Ross MI, et al. Predictors of invasive breast cancer in patients with an initial diagnosis of ductal carcinoma in situ: a guide to selective use of sentinel lymph node biopsy in management of ductal carcinoma in situ. J Am Coll Surg 2005;200:516 –26. 6. Tan JC, McCready DR, Easson AM, et al. Role of sentinel lymph node biopsy in ductal carcinoma-in-situ treated by mastectomy. Ann Surg Oncol 2007;14:638 – 45. 7. Broekhuizen LN, Wijsman JH, Peterse JL, et al. The incidence and significance of micrometastases in lymph nodes of patients with ductal carcinoma in situ and T1a carcinoma of the breast. Eur J Surg Oncol 2006;32:502– 6. 8. Moore KH, Sweeney KJ, Wilson ME, et al. Outcomes for women with ductal carcinoma-in-situ and a positive sentinel node: a multi-institutional audit. Ann Surg Oncol 2007;14:2911–7. 9. Intra M, Rotmensz N, Veronesi P, et al. Sentinel node biopsy is not a standard procedure in ductal carcinoma in situ of the breast: the experience of the European institute of oncology on 854 patients in 10 years. Ann Surg 2008;247:315–9. 10. El-Tamer M, Chun J, Gill M, et al. Incidence and clinical significance of lymph node metastasis detected by cytokeratin immunohistochemical staining in ductal carcinoma in situ. Ann Surg Oncol 2005;12: 254 –9.