Lymph Node Ratio as an Alternative to pN Staging in Node-Positive Breast Cancer

Oncology Center, Universitair Ziekenhuis Brussel, 101 Laarbeeklaan, 1090 Jette, Belgium.
Journal of Clinical Oncology (Impact Factor: 18.43). 02/2009; 27(7):1062-8. DOI: 10.1200/JCO.2008.18.6965
Source: PubMed


In the current pTNM classification system, nodal status of breast cancer is based on the number of involved lymph nodes and does not account for the total number of lymph nodes removed. In this study, we assessed the prognostic value of the lymph node ratio (LNR; ie, ratio of positive over excised lymph nodes) as compared with pN staging and determined its optimal cutoff points.
From the Geneva Cancer Registry, we identified all women diagnosed with node-positive breast cancer between 1980 and 2004 (n = 1,829). The prognostic value of LNRs was calculated for values ranging from 0.05 to 0.95 by Cox regression analysis and validated by bootstrapping. Based on maximum likelihood, we identified cutoff points classifying women into low-, intermediate-, and high-risk LNR groups.
Optimal cutoff points classified patients into low- (< or = 0.20), intermediate- (> 0.20 and < or = 0.65), and high-risk (> 0.65) LNR groups, corresponding to 10-year disease-specific survival rates of 75%, 63%, and 40%, and adjusted mortality risks of 1 (reference), 1.78 (95% CI, 1.46 to 2.18), and 3.21 (95% CI, 2.54 to 4.06), respectively. In contrast to LNR risk categories, survival curves of pN2 and pN3 crossed after 15 years, and their adjusted mortality risks showed overlapping CIs: 2.07 (95% CI, 1.69 to 2.53) and 2.84 (95% CI, 2.23 to 3.61), respectively.
LNR predicts survival after breast cancer more accurately than pN classification and should be considered as an alternative to pN staging.

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    • "In cases where only a few lymph nodes are examined, there is the potential possibility of downstaging the axilla (Vinh-Hung et al, 2009; Danko et al, 2010). The LNR has been proposed as an alternative measure to improve the prognostication system in patients with node-positive disease (Vinh-Hung et al, 2003a, b; Voordeckers et al, 2004; Truong et al, 2005a; Kuru, 2006; Woodward et al, 2006; Truong et al, 2008; Vinh-Hung et al, 2009; Danko et al, 2010; Chagpar et al, 2011; Tausch et al, 2012). Compared with the number-based staging system, the ratio-based staging system exploits additional information on the total number of lymph nodes dissected. "
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    ABSTRACT: Background: To test the hypotheses that breast cancer patients with one to three positive lymph nodes (pN1) consist of heterogeneous prognostic subsets and that the ratio of positive nodes to total nodes dissected (lymph node ratio, LNR) might discriminate patients with a higher risk as candidates for post-mastectomy radiation therapy (PMRT). Methods: Using information from 7741 node-positive patients, we first identified cutoff values of the LNR using the nonparametric bootstrap method. Focusing on 3477 patients with pN1 disease, we then evaluated the clinical relevance of the LNR categorised by the estimated cutoff values (categorised LNR, cLNR). Results: Among 3477 patients with pN1 disease, 3059 and 418 patients were assigned into the low and intermediate cLNR groups, respectively, based on a cutoff value of 0.18. The prognostic factors associated with poor overall survival (OS) included younger age, T2 stage, negative oestrogen/progesterone receptors, high histologic grade, and intermediate cLNR. Post-mastectomy radiation therapy significantly increased OS in patients assigned to the intermediate cLNR (hazard ratio, 0.39; 95% confidence interval, 0.17–0.89; P=0.0248), whereas patients in the low cLNR group derived no additional survival benefit from PMRT. Conclusion: This study suggests that PMRT should be recommended for patients with pN1 disease and an intermediate cLNR.
    British Journal of Cancer 08/2013; 109(5). DOI:10.1038/bjc.2013.465 · 4.84 Impact Factor
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    • "However, an increasing amount of data now supports the prognostic value of LNR in breast cancer, e.g., the International Nodal Ratio Working Group is currently undertaking research to establish the prognostic significance of LNR in breast cancer [19]. Second, there is no consensus on standard cutoff points for LNR [7,9,18,19]. The LNR cutoff points used in this study were based on the report by Vinh-Hung et al., which has been validated in studies in other countries [15-17]. "
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    ABSTRACT: Background To evaluate the prognostic value of axillary lymph node ratio (LNR) as compared to the number of involved nodes (pN stage) in patients with axillary lymph node-positive breast cancer treated with mastectomy without radiation. Methods We performed a retrospective analysis of the clinical data of patients with stage II-III node-positive breast cancer (N=1068) between 1998 and 2007. Locoregional recurrence-free survival (LRFS) and overall survival (OS) were compared based on the LNR and pN staging. Results A total of 780 cases were classified as pN1, 183 as pN2, and 105 as pN3. With respect to LNR, 690 cases had a LNR from 0.01-0.20, 269 cases a LNR from 0.21-0.65, and 109 cases a LNR > 0.65. The median follow-up time was 62 months. Univariate analysis showed that both LNR and pN stage were prognostic factors of LRFS and OS (p<0.05). Multivariate analysis indicated that LNR was an independent prognostic factor of LRFS and OS (p<0.05). pN stage had no significant effect on LRFS or OS (p>0.05). In subgroup analysis, the LNR identified groups of patients with different survival rates based on pN stage. Conclusions LNR is superior to pN staging as a prognostic factor in lymph node-positive breast cancer after mastectomy, and should be used as one of the indications for adjuvant radiation therapy.
    Radiation Oncology 05/2013; 8(119). DOI:10.1186/1748-717X-8-119 · 2.55 Impact Factor
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    • "In exploring the prognostic value of LNR in our series, we elected to use the same cutoff points identified by Vinh-Hung et al. [9], despite as the authors indicated, that different authors have used different cutoff points to classify patients into several risk groups [21] [22] [23]. Table 2 Univariate analysis of the effects of prognostic variables on DFS. "
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    ABSTRACT: Background Breast cancer in Egypt is the most common cancer among women and is the leading cause of cancer mortality. Traditionally, axillary lymph node involvement is considered among the most important prognostic factors in breast cancer. Nonetheless, accumulating evidence suggests that axillary lymph node ratio should be considered as an alternative to classical pN classification. Materials and methods We performed a retrospective analysis of patients with operable node-positive breast cancer, to investigate the prognostic significance of axillary lymph node ratio. Results Five-hundred patients were considered eligible for the analysis. Median follow-up was 35 months (95% CI 32–37 months), the median disease-free survival (DFS) was 49 months (95% CI, 46.4–52.2 months). The classification of patients based on pN staging system failed to prognosticate DFS in the multivariate analysis. Conversely, grade 3 tumors, and the intermediate (>0.20 to ⩽0.65) and high (>0.65) LNR were the only variables that were independently associated with adverse DFS. The overall survival (OS) in this series was 69 months (95% CI 60–77). Conclusion The analysis of outcome of patients with early breast cancer in Egypt identified the adverse prognostic effects of high tumor grade, ER negativity and intermediate and high LNR on DFS. If the utility of the LNR is validated in other studies, it may replace the use of absolute number of axillary lymph nodes.
    Journal of the Egyptian National Cancer Institute 01/2013; 26(1). DOI:10.1016/j.jnci.2013.10.001
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