Prognostic factors in node-negative breast cancer: a review of studies with sample size more than 200 and follow-up more than 5 years.
OBJECTIVE
To review the published literature on prognostic factors in patients with node-negative breast cancer, focusing principally on recent studies with large sample sizes and extended follow-up periods.


BACKGROUND
Although numerous studies have examined prognostic factors in patients with breast cancer, relatively few have dealt specifically with node-negative disease, and interpretation has been limited by small sample size and limited follow-up times.


METHODS
A review of the Medline database from 1996 to 2000 was undertaken, with additional papers published before 1996 identified through review articles. For inclusion in the analysis, papers needed to meet the following core criteria: 200 or more node-negative patients with invasive breast carcinoma; median follow-up time at least 5 years; method of testing and cut-off points specified; overall survival and/or disease-free survival specified; and relative risk or statistical probability values given for comparisons.


RESULTS
Three or more papers that met the core criteria were retrieved for each of 11 potential prognostic factors. Of these, tumor size, tumor grade, cathepsin-D, Ki-67, S-phase fraction, mitotic index, and vascular invasion showed a significant association with survival outcomes; HER2/neu and DNA ploidy showed no significant association; and estrogen receptor status and p53 showed mixed results. Lack of standardization in measurement techniques for many of the markers, including cathepsin-D, Ki-67, HER2/neu, and p53, limited their current clinical usefulness.


CONCLUSIONS
In large studies with extended follow-up periods, tumor size, tumor grade, cathepsin-D, Ki-67, S-phase fraction, mitotic index, and vascular invasion showed a significant association with survival outcome measures in patients with early-stage node-negative breast cancer. Because of technical difficulties and variations in the measurement of many of these factors, tumor size and tumor grade remain the only markers that currently have broad clinical usefulness for this patient group.
Mirza
Attiqa N
AN
Department of Surgical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
Mirza
Nadeem Q
NQ
Vlastos
Georges
G
Singletary
S Eva
SE
D000704:Analysis of Variance; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000235:genetics / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D002402:Cathepsin D; D004247:DNA / Q000235:genetics; D018572:Disease-Free Survival; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D018734:Genes, erbB-2; D016158:Genes, p53; D020022:Genetic Predisposition to Disease; D006801:Humans; D019394:Ki-67 Antigen; D008198:Lymph Nodes; D008940:Mitotic Index; D015999:Multivariate Analysis; D009154:Mutation; D011003:Ploidies; D011336:Probability; D011379:Prognosis; D011960:Receptors, Estrogen / Q000032:analysis; D012306:Risk; D012307:Risk Factors; D016196:S Phase; D016019:Survival Analysis; D013997:Time Factors
D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D011960:Receptors, Estrogen; D004247:DNA; D002402:Cathepsin D