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Methods Using microarray analysis to evaluate our previously established 70-gene prognosis profile, we classified a series of 295 consecutive patients with primary breast carcinomas as having a gene-expression signature associated with either a poor prognosis or a good prognosis. All patients had stage I or II breast cancer and were younger than 53 years old; 151 had lymph-node–negative disease, and 144 had lymph-node–positive disease. We evaluated the predictive power of the prognosis profile using univariable and multivariable statistical analyses. Respiratory Physiology Pdf The Essentials Of Baccalaureate. Results Among the 295 patients, 180 had a poor-prognosis signature and 115 had a good-prognosis signature, and the mean (±SE) overall 10-year survival rates were 54.6±4.4 percent and 94.5±2.6 percent, respectively. At 10 years, the probability of remaining free of distant metastases was 50.6±4.5 percent in the group with a poor-prognosis signature and 85.2±4.3 percent in the group with a good-prognosis signature.
The estimated hazard ratio for distant metastases in the group with a poor-prognosis signature, as compared with the group with the good-prognosis signature, was 5.1 (95 percent confidence interval, 2.9 to 9.0; P. Figure 1 Pattern of Expression of Genes Used to Determine the Prognosis and Clinical Characteristics of 295 Patients with Breast Cancer. Panel A shows the pattern of expression of the 70 marker genes (also referred to as prognosis-classifier genes ) in a series of 295 consecutive patients with breast carcinomas. Each row represents the prognostic profile of the 70 marker genes for one tumor, and each column represents the relative level of expression of one gene.
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The tumors are numbered from 1 to 295 on the y axis, and the genes are numbered from 1 to 70 on the x axis. The genes in the horizontal direction are arrayed in the same order as in our previous study. Red indicates a high level of expression of messenger RNA (mRNA) in the tumor, as compared with the reference level of mRNA, and green indicates a low level of expression.
The dotted line is the previously determined threshold between a good-prognosis signature and a poor-prognosis signature. Tumors are rank-ordered according to their correlation with the previously determined average profile in tumors from patients with a good prognosis. Panel B shows the time in years to distant metastases as a first event for those in whom this occurred, and the total duration of follow-up for all other patients. Panel C shows the lymph-node status (blue marks indicate lymph-node–positive disease, and white lymph-node–negative disease), the number of patients with distant metastases as a first event (blue marks), and the number of patients who died (blue marks). Adjuvant systemic therapy substantially improves disease-free and overall survival in both premenopausal and postmenopausal women up to the age of 70 years with lymph-node–negative or lymph-node–positive breast cancer.
It is generally agreed that patients with poor prognostic features benefit the most from adjuvant therapy. The main prognostic factors in breast cancer are age, tumor size, status of axillary lymph nodes, histologic type of the tumor, pathological grade, and hormone-receptor status. A large number of other factors have been investigated for their potential to predict the outcome of disease, but in general, they have only limited predictive power. Using complementary DNA (cDNA) microarrays to analyze breast-cancer tissue, Perou et al. Identified tumors with distinct patterns of gene expression that they termed “basal type” and “luminal type.” These subgroups differ with respect to the outcome of disease in patients with locally advanced breast cancer. In addition, microarray analysis has been used to distinguish cancers associated with BRCA1 or BRCA2 mutations and to determine estrogen-receptor status and lymph-node status.