Ratios of involved nodes in early breast cancer.
BACKGROUND
The number of lymph nodes found to be involved in an axillary dissection is among the most powerful prognostic factors in breast cancer, but it is confounded by the number of lymph nodes that have been examined. We investigate an idea that has surfaced recently in the literature (since 1999), namely that the proportion of node-positive lymph nodes (or a function thereof) is a much better predictor of survival than the number of excised and node-positive lymph nodes, alone or together.


METHODS
The data were abstracted from 83,686 cases registered in the Surveillance, Epidemiology, and End Results (SEER) program of women diagnosed with nonmetastatic T1-T2 primary breast carcinoma between 1988 and 1997, in whom axillary node dissection was performed. The end-point was death from breast cancer. Cox models based on different expressions of nodal involvement were compared using the Nagelkerke R2 index (R2N). Ratios were modeled as percentage and as log odds of involved nodes. Log odds were estimated in a way that avoids singularities (zero values) by using the empirical logistic transform.


RESULTS
In node-negative cases both the number of nodes excised and the log odds were significant, with hazard ratios of 0.991 (95% confidence interval 0.986-0.997) and 1.150 (1.058-1.249), respectively, but without improving R2N. In node-positive cases the hazard ratios were 1.003-1.088 for the number of involved nodes, 0.966-1.005 for the number of excised nodes, 1.015-1.017 for the percentage, and 1.344-1.381 for the log odds. R2N improved from 0.067 (no nodal covariate) to 0.102 (models based on counts only) and to 0.108 (models based on ratios).


CONCLUSIONS
Ratios are simple optimal predictors, in that they provide at least the same prognostic value as the more traditional staging based on counting of involved nodes, without replacing them with a needlessly complicated alternative. They can be viewed as a per patient standardization in which the number of involved nodes is standardized to the number of nodes excised. In an extension to the study, ratios were validated in a comparison with categorized staging measures using blinded data from the San Jose-Monterey cancer registry. A ratio based prognostic index was also derived. It improved the Nottingham Prognostic Index without compromising on simplicity.
Vinh-Hung
Vincent
V
Oncology Center, Academic Hospital, AZ-VUB, Vrije Universiteit Brussel, Jette, Belgium. conrvhgv@az.vub.ac.be
Verschraegen
Claire
C
Promish
Donald I
DI
Cserni
Gábor
G
Van de Steene
Jan
J
Tai
Patricia
P
Vlastos
Georges
G
Voordeckers
Mia
M
Storme
Guy
G
Royce
Melanie
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000401:mortality* / Q000473:pathology* / Q000601:surgery; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008197:Lymph Node Excision; D008198:Lymph Nodes / Q000473:pathology* / Q000601:surgery; D008207:Lymphatic Metastasis; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D018426:SEER Program; D014481:United States / Q000453:epidemiology