- Email: [email protected]
Sentinel Node Biopsy in Breast Cancer Patients with Large or Multifocal Tumors
2. Lucci A, McCall LM, Beitsch PD, et al. Surgical complications associated with sentinel lymph node dissection (SLND) plus axillary lymph node dissection compared with SLND alone in the American College of Surgeons Oncology Group Trial Z0011. J Clin Oncol. 2007;25:3657-3663. 3. Sacre RA. Clinical evaluation of axillary lymph nodes compared to
surgical and pathological findings. Eur J Surg Oncol. 1986;12:169-173. 4. Wahl RL, Siegel BA, Coleman RE, Gatsonis CG, PET Study Group. Prospective multicenter study of axillary nodal staging by positron emission tomography in breast cancer: a report of the staging breast cancer with PET Study Group. J Clin Oncol. 2004;22:277-285.
5. Krishnamurthy S, Sneige N, Bedi DG, et al. Role of ultrasoundguided fine-needle aspiration of indeterminate and suspicious axillary lymph nodes in the initial staging of breast carcinoma. Cancer. 2002;95: 982-988.
SENTINEL NODE BIOPSY Sentinel Node Biopsy in Breast Cancer Patients with Large or Multifocal Tumors Meretoja TJ, Leidenius MH, Heikkil PS, et al (Helsinki Univ Central Hosp, Finland) Ann Surg Oncol 16:1148-1155, 2009
Background.—The axillary recurrence (AR) rate after negative sentinel node biopsy (SNB) in patients with high risk of axillary metastases is largely unknown. The aim of this study was to analyze the risk factors for isolated AR after negative SNB with special interest in large or multifocal tumors. Methods.—A prospective SNB registry was analyzed for 2,408 invasive breast cancer patients operated between 2001 and 2007. No axillary clearance was performed in 1,309 cases with a negative SNB, including 1,138 small unifocal tumors, 121 small multifocal tumors, 48 large unifocal tumors, and 2 large multifocal tumors. Results.—Six (0.5%) isolated AR were observed during a median followup of 43 months. Four (0.4%) patients with small unifocal tumors and two
(1.6%) with small multifocal tumors had isolated AR (p ¼ 0.179). None of the patients with large unifocal or multifocal tumors had isolated AR. Instead of tumor size and multifocality, estrogen receptor negativity (p < 0.001), nuclear grade III (p < 0.001), Her-2 status (p ¼ 0.002), no radiotherapy (p ¼ 0.005), and mastectomy (p ¼ 0.005) were found to be associated with AR. Conclusions.—A remarkable proportion of patients with large unifocal tumors and small multifocal tumors may avoid unnecessary AC due to tumor negative SNB, without an excessive risk of AR. Sentinel node biopsy (SNB) has become the standard of care for early-stage breast cancer. Both the Surveillance, Epidemiology, and End Results cancer registry and the National Cancer Database have rapidly adopted SNB for axillary staging in patients with breast cancer.1,2 Even though there has been widespread acceptance of the SNB procedure, controversies still persist regarding appropriate patient selection. To address the various issues surrounding SNB, the American Society of Clinical Oncology (ASCO) published
guidelines for (SNB) based on all the relevant clinical data that had been reported prior to the time of publication.3 Meretoja and colleagues have added further data to support the use of SNB in certain clinical situations where previous clinical evidence was not definitive. Their focus was to determine the utility of SNB in 4 clinical situations: (1) small (#3 cm) unifocal tumors, (2) small (#3 cm) multifocal tumors, (3) large (>3 cm) unifocal tumors, and (4) large (>3 cm) multifocal tumors. Their measure of clinical efficacy was the rate of ARs in patients with a negative SNB. In 1317 patients with negative SLNs, only 6 (0.5%) had an isolated AR, and 4 (0.3%) had a local recurrence and an AR. These results compare favorably to what has already been reported in the literature.4 Interestingly, most ARs (7 of the 10) occurred in patients with small unifocal tumors, with the remaining 3 occurring in patients with small multifocal tumors. This may relate to the fact that there were only 50 patients (4%) with large tumors who were SLN negative. On the other hand, it does support the accuracy of
Breast Diseases: A Year BookÒ Quarterly Vol 21 No 1 2010
55
SNB in patients with large tumors. Meretoja and colleagues also tried to identify risk factors for AR. Unfortunately, with these small numbers of ARs, no true conclusions can be drawn. Even though the total number of patients with multifocal/multicentric disease was only 174, these data add further support to the hypothesis that SNB is appropriate for patients with multifocal/multicentric disease. There is a growing body of literature that demonstrates SNB can be done with a low false-negative rate and low risk of ARs in patients with multifocal/ multicentric tumors.5,6 Therefore, multifocal/multicentric disease should no longer be viewed as a contraindication to SNB. In this study by Meretoja and colleagues, the number of patients with large multifocal tumors was only 32. Of these 32 patients, only 2 (6%) were SLN negative; therefore, the authors concluded that SNB should not be performed in this group of patients. In addition, the authors acknowledged that this information is not always known preoperatively. Overall, with such a small population of patients that fit into this category, a conclusion regarding this patient population is difficult, and I think that clinical judgment should prevail. With the advent of axillary ultrasonography as a method to evaluate the axilla, patients with large multifocal tumors would be excellent candidates for preoperative axillary evaluation. Patients with clinically negative axillas and negative ultrasounds could be selected to undergo SNB, instead of subjecting all of these patients to axillary dissection.
56
The main difficulty in this article is the authors’ definition of large tumors. Almost all previous studies of SLN biopsy rely on T stage to evaluate the utility of SLN biopsy. Here, Meretoja and colleagues defined large tumors as greater than 3 cm (mean tumor size ¼ 4.4 cm), which makes their data difficult to compare to other studies. I think that most surgeons would perform an SNB in a T2 lesion or employ preoperative axillary ultrasonography if there were any clinical suspicion of lymph node metastases. The ASCO guidelines currently recommend SNB for patients with T1 or T2 tumors but not for those with T3 or T4 tumors. This article by Meretoja and colleagues did not state the number of patients with tumors larger than 5 cm; therefore, no real conclusions can be drawn for T3 or T4 tumors. Of course, the large majority of patients with T3 or T4 tumors will have clinically positive lymph nodes and undergo neoadjuvant systemic therapy prior to their surgery. There is mounting evidence that those patients with clinical T3N0 tumors can be treated with SNB before or after systemic therapy, with good results,7 whereas the treatment of the axilla in those patients with clinically positive SLNs prior to neoadjuvant systemic therapy is still controversial and will need to be evaluated by a large clinical trial. B. A. Pockaj, MD
References 1. Rescigno J, Zampell JC, Axelrod D. Patterns of axillary surgical care for
Breast Diseases: A Year BookÒ Quarterly Vol 21 No 1 2010
breast cancer in the era of sentinel lymph node biopsy. Ann Surg Oncol. 2009;16:687-696. 2. Chen AY, Halpern MT, Schrag NM, Stewart A, Leitch M, Ward E. Disparities and trends in sentinel lymph node biopsy among early-stage breast cancer patients (1998-2005). J Natl Cancer Inst. 2008;100: 462-474. 3. Lyman GH, Guiliano AE, Sennerfeld MR. American Society of Clinical Oncology. American Society of Clinical Oncology guideline recommendations for sentinel lymph node biopsy in early-stage breast cancer. J Clin Oncol. 2005;23: 7703-7720. 4. van der Ploeg IM, Nieweg OE, van Rijk MC, Valde´s Olmos RA, Kroon BB. Axillary recurrence after a tumour-negative sentinel node biopsy in breast cancer patients: a systemic review and meta-analysis of the literature. Eur J Surg Oncol. 2008;34: 1277-1284. 5. Carpenter S, Fraser J, Fleming M, Gray R, Halyard M, Pockaj B. Optimal treatment of multiple ipsilateral primary breast cancers. Am J Surg. 2008;196:530-536. 6. Knauer M, Konstantiniuk P, Haid A, et al. Multicentric breast cancer: a new indication for sentinel node biopsy–a multi-institutional validation study. J Clin Oncol. 2006; 24:3374-3380. 7. Hunt KK, Yi M, Mittendorf EA, et al. Sentinel lymph node surgery after neoadjuvant chemotherapy is accurate and reduces the need for axillary dissection in breast cancer patients. [published online ahead of print August 27, 2009]. Ann Surg. doi:10.1097/ SLA.0b013e3181b8fd5e.
surgical and pathological findings. Eur J Surg Oncol. 1986;12:169-173. 4. Wahl RL, Siegel BA, Coleman RE, Gatsonis CG, PET Study Group. Prospective multicenter study of axillary nodal staging by positron emission tomography in breast cancer: a report of the staging breast cancer with PET Study Group. J Clin Oncol. 2004;22:277-285.
5. Krishnamurthy S, Sneige N, Bedi DG, et al. Role of ultrasoundguided fine-needle aspiration of indeterminate and suspicious axillary lymph nodes in the initial staging of breast carcinoma. Cancer. 2002;95: 982-988.
SENTINEL NODE BIOPSY Sentinel Node Biopsy in Breast Cancer Patients with Large or Multifocal Tumors Meretoja TJ, Leidenius MH, Heikkil PS, et al (Helsinki Univ Central Hosp, Finland) Ann Surg Oncol 16:1148-1155, 2009
Background.—The axillary recurrence (AR) rate after negative sentinel node biopsy (SNB) in patients with high risk of axillary metastases is largely unknown. The aim of this study was to analyze the risk factors for isolated AR after negative SNB with special interest in large or multifocal tumors. Methods.—A prospective SNB registry was analyzed for 2,408 invasive breast cancer patients operated between 2001 and 2007. No axillary clearance was performed in 1,309 cases with a negative SNB, including 1,138 small unifocal tumors, 121 small multifocal tumors, 48 large unifocal tumors, and 2 large multifocal tumors. Results.—Six (0.5%) isolated AR were observed during a median followup of 43 months. Four (0.4%) patients with small unifocal tumors and two
(1.6%) with small multifocal tumors had isolated AR (p ¼ 0.179). None of the patients with large unifocal or multifocal tumors had isolated AR. Instead of tumor size and multifocality, estrogen receptor negativity (p < 0.001), nuclear grade III (p < 0.001), Her-2 status (p ¼ 0.002), no radiotherapy (p ¼ 0.005), and mastectomy (p ¼ 0.005) were found to be associated with AR. Conclusions.—A remarkable proportion of patients with large unifocal tumors and small multifocal tumors may avoid unnecessary AC due to tumor negative SNB, without an excessive risk of AR. Sentinel node biopsy (SNB) has become the standard of care for early-stage breast cancer. Both the Surveillance, Epidemiology, and End Results cancer registry and the National Cancer Database have rapidly adopted SNB for axillary staging in patients with breast cancer.1,2 Even though there has been widespread acceptance of the SNB procedure, controversies still persist regarding appropriate patient selection. To address the various issues surrounding SNB, the American Society of Clinical Oncology (ASCO) published
guidelines for (SNB) based on all the relevant clinical data that had been reported prior to the time of publication.3 Meretoja and colleagues have added further data to support the use of SNB in certain clinical situations where previous clinical evidence was not definitive. Their focus was to determine the utility of SNB in 4 clinical situations: (1) small (#3 cm) unifocal tumors, (2) small (#3 cm) multifocal tumors, (3) large (>3 cm) unifocal tumors, and (4) large (>3 cm) multifocal tumors. Their measure of clinical efficacy was the rate of ARs in patients with a negative SNB. In 1317 patients with negative SLNs, only 6 (0.5%) had an isolated AR, and 4 (0.3%) had a local recurrence and an AR. These results compare favorably to what has already been reported in the literature.4 Interestingly, most ARs (7 of the 10) occurred in patients with small unifocal tumors, with the remaining 3 occurring in patients with small multifocal tumors. This may relate to the fact that there were only 50 patients (4%) with large tumors who were SLN negative. On the other hand, it does support the accuracy of
Breast Diseases: A Year BookÒ Quarterly Vol 21 No 1 2010
55
SNB in patients with large tumors. Meretoja and colleagues also tried to identify risk factors for AR. Unfortunately, with these small numbers of ARs, no true conclusions can be drawn. Even though the total number of patients with multifocal/multicentric disease was only 174, these data add further support to the hypothesis that SNB is appropriate for patients with multifocal/multicentric disease. There is a growing body of literature that demonstrates SNB can be done with a low false-negative rate and low risk of ARs in patients with multifocal/ multicentric tumors.5,6 Therefore, multifocal/multicentric disease should no longer be viewed as a contraindication to SNB. In this study by Meretoja and colleagues, the number of patients with large multifocal tumors was only 32. Of these 32 patients, only 2 (6%) were SLN negative; therefore, the authors concluded that SNB should not be performed in this group of patients. In addition, the authors acknowledged that this information is not always known preoperatively. Overall, with such a small population of patients that fit into this category, a conclusion regarding this patient population is difficult, and I think that clinical judgment should prevail. With the advent of axillary ultrasonography as a method to evaluate the axilla, patients with large multifocal tumors would be excellent candidates for preoperative axillary evaluation. Patients with clinically negative axillas and negative ultrasounds could be selected to undergo SNB, instead of subjecting all of these patients to axillary dissection.
56
The main difficulty in this article is the authors’ definition of large tumors. Almost all previous studies of SLN biopsy rely on T stage to evaluate the utility of SLN biopsy. Here, Meretoja and colleagues defined large tumors as greater than 3 cm (mean tumor size ¼ 4.4 cm), which makes their data difficult to compare to other studies. I think that most surgeons would perform an SNB in a T2 lesion or employ preoperative axillary ultrasonography if there were any clinical suspicion of lymph node metastases. The ASCO guidelines currently recommend SNB for patients with T1 or T2 tumors but not for those with T3 or T4 tumors. This article by Meretoja and colleagues did not state the number of patients with tumors larger than 5 cm; therefore, no real conclusions can be drawn for T3 or T4 tumors. Of course, the large majority of patients with T3 or T4 tumors will have clinically positive lymph nodes and undergo neoadjuvant systemic therapy prior to their surgery. There is mounting evidence that those patients with clinical T3N0 tumors can be treated with SNB before or after systemic therapy, with good results,7 whereas the treatment of the axilla in those patients with clinically positive SLNs prior to neoadjuvant systemic therapy is still controversial and will need to be evaluated by a large clinical trial. B. A. Pockaj, MD
References 1. Rescigno J, Zampell JC, Axelrod D. Patterns of axillary surgical care for
Breast Diseases: A Year BookÒ Quarterly Vol 21 No 1 2010
breast cancer in the era of sentinel lymph node biopsy. Ann Surg Oncol. 2009;16:687-696. 2. Chen AY, Halpern MT, Schrag NM, Stewart A, Leitch M, Ward E. Disparities and trends in sentinel lymph node biopsy among early-stage breast cancer patients (1998-2005). J Natl Cancer Inst. 2008;100: 462-474. 3. Lyman GH, Guiliano AE, Sennerfeld MR. American Society of Clinical Oncology. American Society of Clinical Oncology guideline recommendations for sentinel lymph node biopsy in early-stage breast cancer. J Clin Oncol. 2005;23: 7703-7720. 4. van der Ploeg IM, Nieweg OE, van Rijk MC, Valde´s Olmos RA, Kroon BB. Axillary recurrence after a tumour-negative sentinel node biopsy in breast cancer patients: a systemic review and meta-analysis of the literature. Eur J Surg Oncol. 2008;34: 1277-1284. 5. Carpenter S, Fraser J, Fleming M, Gray R, Halyard M, Pockaj B. Optimal treatment of multiple ipsilateral primary breast cancers. Am J Surg. 2008;196:530-536. 6. Knauer M, Konstantiniuk P, Haid A, et al. Multicentric breast cancer: a new indication for sentinel node biopsy–a multi-institutional validation study. J Clin Oncol. 2006; 24:3374-3380. 7. Hunt KK, Yi M, Mittendorf EA, et al. Sentinel lymph node surgery after neoadjuvant chemotherapy is accurate and reduces the need for axillary dissection in breast cancer patients. [published online ahead of print August 27, 2009]. Ann Surg. doi:10.1097/ SLA.0b013e3181b8fd5e.