Disease-Free Survival and Prognostic Significance of Metastatic Lymph Node Ratio in T1-T2 N Positive Breast Cancer Patients. A Population Registry-Based Study in a European Country
ABSTRACT The ratio of positive lymph nodes between the total number of harvested lymph nodes (metastatic lymph node ratio, MLNR) has been proposed as an alternative to the total number of lymph nodes alone in predicting outcomes for patients with breast cancer. Because there can be differences between European and non-European populations, the authors present the first study analyzing MLNR influence over disease-free survival (DFS) by using a population-based cancer registry in a European country.
Data from 441 patients with T1-2 N1-3 breast cancer included in the Castellon Cancer Registry (Comunidad Valenciana, Spain) were used. Cumulative DFS was determined using the Kaplan-Meier method, with univariate comparisons between groups through the log-rank test. The Cox proportional hazards model was used for multivariate analysis.
At univariate analysis, factors influencing the 10-year DFS rate were tumor size, conservative or nonconservative surgery, histologic grade, histologic type, radiotherapy, tamoxifen, estrogen and progesterone receptor status, p53 status, total number of positive lymph nodes, and MLNR. At multivariate analysis, tumor size, MLNR, and progesterone receptor status were revealed to be independent prognostic factors; the metastatic lymph node ratio was the most notably independent factor (hazard ratio 1.02, 5.21, and 0.61, respectively).
MLNR is a stronger prognostic factor for recurrence than the total number of positive lymph nodes in T1-T2 N1-3 breast cancer.
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ABSTRACT: We evaluated the prognostic significance of lymph node ratio (LNR), number of metastatic lymph nodes divided by number of removed nodes in 924 breast carcinoma patients with 1-3 metastatic axillary lymph node(s). The most significant LNR threshold value separating patients in low- and high-risk groups with significant survival difference was 0.20 for disease-free survival (P < 0.001), 0.30 for locoregional recurrence-free survival (P < 0.001), and 0.15 for distant metastasis-free survival (P < 0.001), and the patients with lower LNR had better survival. All three LNR threshold values had independent prognostic significance in Cox analysis (P < 0.001 for all three of them). In conclusion, LNR is a useful tool in separating breast carcinoma patients with 1-3 metastatic lymph node(s) into low- and high-risk prognostic groups.10/2011; 2011:645450. DOI:10.5402/2011/645450
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ABSTRACT: Nodal ratio (NR) is defined as the number of involved nodes to the number of nodes examined. There is limited information on the application of NR on population data. Previous reports in breast cancer generally analyzed one to three positive axillary nodes as a single group. This study investigates whether one to three positive axillary nodes is a homogeneous group in prognosis by comparing one to two positive nodes to three positive nodes. The population‐based registry of a Canadian province from 1981 through 1995 was searched. As the reliability of nodal assessment depends on the number of nodes sampled, we also studied the subgroup of patients with greater than or equal to eight nodes dissected. Of a total of 5,996 breast cancer patients, 1187 had one to three positive axillary nodes. The 263 patients with three positive nodes compared to the 924 patients with one to two nodes fared worse with a significantly reduced cause‐specific survival (CSS) and overall survival (OS). Patients with one to two positive nodes had similar CSS (p = 0.31) and OS (p = 0.63). Among those with greater than or equal to eight nodes dissected, there were 677 patients with one to two positive nodes. CSS and OS were not significantly different between one versus two positive nodes (p = 0.16 and 0.34, respectively), but with NR, the corresponding p values were 0.0068 and 0.08, respectively. The cutoff value of NR 0.15 was found to be most useful and confirmed by the validation dataset. NR is able to segregate patients better than the absolute number of positive nodes used in the current staging system. NR should be incorporated into the staging system.The Breast Journal 11/2012; 18(6). DOI:10.1111/tbj.12010 · 1.43 Impact Factor
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ABSTRACT: Intratumoral heterogeneity may help drive resistance to targeted therapies in cancer. In breast cancer, the presence of nodal metastases is a key indicator of poorer overall survival. The aim of this study was to identify somatic genetic alterations in early dissemination of breast cancer by whole genome next generation sequencing (NGS) of a primary breast tumor, a matched locally-involved axillary lymph node and healthy normal DNA from blood. Whole genome NGS was performed on 12 µg (range 11.1-13.3 µg) of DNA isolated from fresh-frozen primary breast tumor, axillary lymph node and peripheral blood following the DNA nanoball sequencing protocol. Single nucleotide variants, insertions, deletions, and substitutions were identified through a bioinformatic pipeline and compared to CIN25, a key set of genes associated with tumor metastasis. Whole genome sequencing revealed overlapping variants between the tumor and node, but also variants that were unique to each. Novel mutations unique to the node included those found in two CIN25 targets, TGIF2 and CCNB2, which are related to transcription cyclin activity and chromosomal stability, respectively, and a unique frameshift in PDS5B, which is required for accurate sister chromatid segregation during cell division. We also identified dominant clonal variants that progressed from tumor to node, including SNVs in TP53 and ARAP3, which mediates rearrangements to the cytoskeleton and cell shape, and an insertion in TOP2A, the expression of which is significantly associated with tumor proliferation and can segregate breast cancers by outcome. This case study provides preliminary evidence that primary tumor and early nodal metastasis have largely overlapping somatic genetic alterations. There were very few mutations unique to the involved node. However, significant conclusions regarding early dissemination needs analysis of a larger number of patient samples.PLoS ONE 12/2014; 9(12):e115346. DOI:10.1371/journal.pone.0115346 · 3.53 Impact Factor