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The number of positive nodes and the ratio of positive to excised nodes are significant predictors of survival in women with micrometastatic node-positive breast cancer
5. Beriwal S, Soran A, Kocer B, Wilson JW, Ahrendt GM, Johnson R. Factors that predict the burden of axillary disease in breast cancer
The number of positive nodes and the ratio of positive to excised nodes are significant predictors of survival in women with micrometastatic nodepositive breast cancer Truong PT, Vinh-Hung V, Cserni G, et al (Univ of British Columbia, Victoria, Canada; Vrije Universiteit, Brussel, Jette, Belgium; Bcs-Kiskun County Hosp, Kecskemt, Hungary; et al) Eur J Cancer 44:1670-1677, 2008
Background.—To evaluate the prognostic impact of the number of positive nodes and the lymph node ratio (LNR) of positive to excised nodes on survival in women diagnosed with nodal micrometastatic breast cancer before the era of widespread sentinel lymph node biopsy. Methods.—Subjects were 62,551 women identified by the Surveillance Epidemiology and End Results database, diagnosed with pT1–2pN0-1 breast cancer between 1988 and 1997. Kaplan–Meier breast cancer-specific survival (BCSS) and overall survival (OS) were compared between three cohorts: node-negative (pN0, n ¼ 57,980) nodal micrometastasis all #2 mm (pNmic, N ¼ 1818), and macroscopic nodal metastasis >2 mm but <2 cm (pNmac, n ¼ 2753). Nodal subgroups were examined by the number of positive nodes (1–3 versus $4) and the LNR (#0.25 versus >0.25). Results.—Median follow-up was 7.3 yr. Ten-year BCSS and OS in
patients with a positive sentinel node. Am J Clin Oncol. 2008;31:34-38. 6. Rivers AK, Griffith KA, Hunt KK, et al. Clinicopathologic features associated
pNmic breast cancer were significantly lower compared to pN0 disease (BCSS 82.3% versus 91.9%, p < 0.001 and OS 68.1% versus 75.7%, p < 0.001). BCSS and OS with pNmic disease progressively declined with increasing number of positive nodes and increasing LNR. OS with pNmic was similar to pNmac disease when matched by the number of positive nodes and by the LNR. Both pN-based and LNR-based classifications were significantly prognostic of BCSS and OS on Cox regression multivariate analysis. Conclusion.—Nodal micrometastasis is associated with poorer survival compared to pN0 disease. Mortality hazards with nodal micrometastasis increased with increasing number of positive nodes and increasing LNR. The number of positive nodes and the LNR should be considered in risk estimates for patients with nodal micrometastatic breast cancer. Truong and colleagues used the SEER database to evaluate the treatment of patents diagnosed during the pre–sentinel lymph node biopsy era. Most patients had their lymph node disease assessed by hematoxylineosin staining of bivalved lymph nodes after axillary dissection. The authors compared dichotomized groups rather than studying axillary disease as a continuous variable to determine the statistical impact of node involvement. Only 7% of the patients had positive axillary nodes, a much lower than expected rate for T1-2N0-1 disease. Thirty-eight percent of the
with having four or more metastatic axillary nodes in breast cancer patients with a positive sentinel lymph node. Ann Surg Oncol. 2006;13:36-44.
patients with nodal disease had only micrometastatic disease, which was a higher rate than expected.1 Comparing patients with microscopic nodal disease with those with macroscopic nodal disease revealed similar outcomes for patients with 4 or more involved nodes. However, multinodal involvement by micrometastases only is a very unusual circumstance. In another study, this scenario accounted for only 4 of 2150 breast cancer patients who were staged with a sentinel node biopsy using 150-mm serial sections, with a 30% overall incidence of node involvement noted.1 Among patients with micrometastases seen in the sentinel node, less than 1% had additional micrometastases identified on completion axillary dissection.1 Extrapolating this rate to the SEER data in the study by Truong and colleagues, one would expect to find less than 18 patients with multinodal micrometastases in their cohort of 1818 women. Although the number of patients with this description was not included, one would not expect a cohort large enough to make a statistically significant survival comparison to patients with macrometastases. As a consequence, the conclusions in this study may not be based upon accurate data. It is likely that the microscopic nodal disease group, particularly those with multinodal involvement, included some patients who also had macroscopically involved nodes. This
Breast Diseases: A Year BookÒ Quarterly Vol 20 No 1 2009
69
would explain the convergence of the survival curves for patients with macroscopic or microscopic involvement of 4 or more nodes. This study, therefore, does not add support to the position that we should be offering our node-positive patients more extensive axillary surgery based upon the identification of positive nodes. The resolution limits of identifying nodal disease continue to increase with the use of immunohistochemistry and molecular assays, such as rt-PCR. Although the clinical significance of such findings remains unclear, it is apparent that prognosis is related to the extent of disease, in terms of both the number of involved nodes and the disease burden within the involved nodes. Nomograms have been devised to make predictions regarding residual disease following sentinel lymphadenectomy,2 but none have addressed the more important issue of how the removal of additional microscopic disease should affect other therapeutic decisions. With
A Scoring System to Predict Nonsentinel Lymph Node Status in Breast Cancer Patients with Metastatic Sentinel Lymph Nodes: A Comparison with Other Scoring Systems Cho J, Han W, Lee JW, et al (Keimyung Univ College of Medicine, Daegu, Korea; Seoul Natl Univ Hosp, Korea) Ann Surg Oncol 15:2278-2286, 2008
Background.—The majority of breast cancer patients with metastatic sentinel lymph node (SLN) do not
70
mature survival data from the National Surgical Adjuvant Breast and Bowel Project B04 trial and more recent reports describing low rates of regional recurrence with observation of the axilla following excision of involved sentinel nodes, clinicians should understand that more aggressive axillary surgery provides very little or no therapeutic benefit for breast cancer patients.3-6 D. J. Winchester, MD
References 1. van Rijk MC, Peterse JL, Nieweg OE, Oldenburg HS, Rutgers EJ, Kroon BB. Additional axillary metastases and stage migration in breast cancer patients with micrometastases or submicrometastases in sentinel lymph nodes. Cancer. 2006;107:467-471. 2. Van Zee KJ, Manasseh DM, Bevilacqua JL, et al. A nomogram for predicting the likelihood of additional nodal metastases in breast cancer patients with a positive sentinel node
harbor additional metastasis in nonSLN. It is unclear which patients with metastatic SLN require axillary lymph node dissection (ALND). The aim of this study was to identify predictive factors of non-SLN metastasis and to develop a scoring system. Methods.—The training dataset consisted of 184 breast cancer patients. The independent validation dataset consisted of 82 breast cancer patients. The receiver operating characteristic (ROC) curve was drawn and the area under the ROC curve (AUC) was calculated to assess the discriminative power of the scoring systems.
Breast Diseases: A Year BookÒ Quarterly Vol 20 No 1 2009
biopsy. Ann Surg Oncol. 2003;10: 1140-1151. 3. Fisher B, Jeong JH, Anderson S, Bryant J, Fisher ER, Wolmark N. Twenty-five-year follow-up of a randomized trial comparing radical mastectomy, total mastectomy, and total mastectomy followed by irradiation. N Engl J Med. 2002;347: 567-575. 4. 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;240:462-471. 5. Jeruss JS, Winchester DJ, Sener SF, et al. Axillary recurrence after sentinel node biopsy. Ann Surg Oncol. 2005;12:34-40. 6. Hwang RF, Gonzalez-Angulo AM, Yi M, et al. Low locoregional failure rates in selected breast cancer patients with tumor-positive sentinel lymph nodes who do not undergo completion axillary dissection. Cancer. 2007;110:723-730.
Results.—Multivariate analysis revealed that non-SLN status was predicted by preoperative ultrasonographic findings of the axilla, lymphovascular invasion, increasing tumor size, increasing number of metastatic SLN, and decreasing number of nonmetastatic SLN. Based on multivariate logistic regression, we developed a scoring system for predicting nonSLN metastasis. The AUC for our scoring system was superior to other published scoring systems when identical validation data were applied. Conclusion.—The likelihood of metastatic non-SLN correlated with
The number of positive nodes and the ratio of positive to excised nodes are significant predictors of survival in women with micrometastatic nodepositive breast cancer Truong PT, Vinh-Hung V, Cserni G, et al (Univ of British Columbia, Victoria, Canada; Vrije Universiteit, Brussel, Jette, Belgium; Bcs-Kiskun County Hosp, Kecskemt, Hungary; et al) Eur J Cancer 44:1670-1677, 2008
Background.—To evaluate the prognostic impact of the number of positive nodes and the lymph node ratio (LNR) of positive to excised nodes on survival in women diagnosed with nodal micrometastatic breast cancer before the era of widespread sentinel lymph node biopsy. Methods.—Subjects were 62,551 women identified by the Surveillance Epidemiology and End Results database, diagnosed with pT1–2pN0-1 breast cancer between 1988 and 1997. Kaplan–Meier breast cancer-specific survival (BCSS) and overall survival (OS) were compared between three cohorts: node-negative (pN0, n ¼ 57,980) nodal micrometastasis all #2 mm (pNmic, N ¼ 1818), and macroscopic nodal metastasis >2 mm but <2 cm (pNmac, n ¼ 2753). Nodal subgroups were examined by the number of positive nodes (1–3 versus $4) and the LNR (#0.25 versus >0.25). Results.—Median follow-up was 7.3 yr. Ten-year BCSS and OS in
patients with a positive sentinel node. Am J Clin Oncol. 2008;31:34-38. 6. Rivers AK, Griffith KA, Hunt KK, et al. Clinicopathologic features associated
pNmic breast cancer were significantly lower compared to pN0 disease (BCSS 82.3% versus 91.9%, p < 0.001 and OS 68.1% versus 75.7%, p < 0.001). BCSS and OS with pNmic disease progressively declined with increasing number of positive nodes and increasing LNR. OS with pNmic was similar to pNmac disease when matched by the number of positive nodes and by the LNR. Both pN-based and LNR-based classifications were significantly prognostic of BCSS and OS on Cox regression multivariate analysis. Conclusion.—Nodal micrometastasis is associated with poorer survival compared to pN0 disease. Mortality hazards with nodal micrometastasis increased with increasing number of positive nodes and increasing LNR. The number of positive nodes and the LNR should be considered in risk estimates for patients with nodal micrometastatic breast cancer. Truong and colleagues used the SEER database to evaluate the treatment of patents diagnosed during the pre–sentinel lymph node biopsy era. Most patients had their lymph node disease assessed by hematoxylineosin staining of bivalved lymph nodes after axillary dissection. The authors compared dichotomized groups rather than studying axillary disease as a continuous variable to determine the statistical impact of node involvement. Only 7% of the patients had positive axillary nodes, a much lower than expected rate for T1-2N0-1 disease. Thirty-eight percent of the
with having four or more metastatic axillary nodes in breast cancer patients with a positive sentinel lymph node. Ann Surg Oncol. 2006;13:36-44.
patients with nodal disease had only micrometastatic disease, which was a higher rate than expected.1 Comparing patients with microscopic nodal disease with those with macroscopic nodal disease revealed similar outcomes for patients with 4 or more involved nodes. However, multinodal involvement by micrometastases only is a very unusual circumstance. In another study, this scenario accounted for only 4 of 2150 breast cancer patients who were staged with a sentinel node biopsy using 150-mm serial sections, with a 30% overall incidence of node involvement noted.1 Among patients with micrometastases seen in the sentinel node, less than 1% had additional micrometastases identified on completion axillary dissection.1 Extrapolating this rate to the SEER data in the study by Truong and colleagues, one would expect to find less than 18 patients with multinodal micrometastases in their cohort of 1818 women. Although the number of patients with this description was not included, one would not expect a cohort large enough to make a statistically significant survival comparison to patients with macrometastases. As a consequence, the conclusions in this study may not be based upon accurate data. It is likely that the microscopic nodal disease group, particularly those with multinodal involvement, included some patients who also had macroscopically involved nodes. This
Breast Diseases: A Year BookÒ Quarterly Vol 20 No 1 2009
69
would explain the convergence of the survival curves for patients with macroscopic or microscopic involvement of 4 or more nodes. This study, therefore, does not add support to the position that we should be offering our node-positive patients more extensive axillary surgery based upon the identification of positive nodes. The resolution limits of identifying nodal disease continue to increase with the use of immunohistochemistry and molecular assays, such as rt-PCR. Although the clinical significance of such findings remains unclear, it is apparent that prognosis is related to the extent of disease, in terms of both the number of involved nodes and the disease burden within the involved nodes. Nomograms have been devised to make predictions regarding residual disease following sentinel lymphadenectomy,2 but none have addressed the more important issue of how the removal of additional microscopic disease should affect other therapeutic decisions. With
A Scoring System to Predict Nonsentinel Lymph Node Status in Breast Cancer Patients with Metastatic Sentinel Lymph Nodes: A Comparison with Other Scoring Systems Cho J, Han W, Lee JW, et al (Keimyung Univ College of Medicine, Daegu, Korea; Seoul Natl Univ Hosp, Korea) Ann Surg Oncol 15:2278-2286, 2008
Background.—The majority of breast cancer patients with metastatic sentinel lymph node (SLN) do not
70
mature survival data from the National Surgical Adjuvant Breast and Bowel Project B04 trial and more recent reports describing low rates of regional recurrence with observation of the axilla following excision of involved sentinel nodes, clinicians should understand that more aggressive axillary surgery provides very little or no therapeutic benefit for breast cancer patients.3-6 D. J. Winchester, MD
References 1. van Rijk MC, Peterse JL, Nieweg OE, Oldenburg HS, Rutgers EJ, Kroon BB. Additional axillary metastases and stage migration in breast cancer patients with micrometastases or submicrometastases in sentinel lymph nodes. Cancer. 2006;107:467-471. 2. Van Zee KJ, Manasseh DM, Bevilacqua JL, et al. A nomogram for predicting the likelihood of additional nodal metastases in breast cancer patients with a positive sentinel node
harbor additional metastasis in nonSLN. It is unclear which patients with metastatic SLN require axillary lymph node dissection (ALND). The aim of this study was to identify predictive factors of non-SLN metastasis and to develop a scoring system. Methods.—The training dataset consisted of 184 breast cancer patients. The independent validation dataset consisted of 82 breast cancer patients. The receiver operating characteristic (ROC) curve was drawn and the area under the ROC curve (AUC) was calculated to assess the discriminative power of the scoring systems.
Breast Diseases: A Year BookÒ Quarterly Vol 20 No 1 2009
biopsy. Ann Surg Oncol. 2003;10: 1140-1151. 3. Fisher B, Jeong JH, Anderson S, Bryant J, Fisher ER, Wolmark N. Twenty-five-year follow-up of a randomized trial comparing radical mastectomy, total mastectomy, and total mastectomy followed by irradiation. N Engl J Med. 2002;347: 567-575. 4. 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;240:462-471. 5. Jeruss JS, Winchester DJ, Sener SF, et al. Axillary recurrence after sentinel node biopsy. Ann Surg Oncol. 2005;12:34-40. 6. Hwang RF, Gonzalez-Angulo AM, Yi M, et al. Low locoregional failure rates in selected breast cancer patients with tumor-positive sentinel lymph nodes who do not undergo completion axillary dissection. Cancer. 2007;110:723-730.
Results.—Multivariate analysis revealed that non-SLN status was predicted by preoperative ultrasonographic findings of the axilla, lymphovascular invasion, increasing tumor size, increasing number of metastatic SLN, and decreasing number of nonmetastatic SLN. Based on multivariate logistic regression, we developed a scoring system for predicting nonSLN metastasis. The AUC for our scoring system was superior to other published scoring systems when identical validation data were applied. Conclusion.—The likelihood of metastatic non-SLN correlated with