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SUMMARY BACKGROUND DATA: The purpose of this study was to determine the type of relationship between tumor size and mortality in early breast carcinoma. METHODS: The data was abstracted from 83,686 cases registered in the Surveillance, Epidemiology, and End Results Program of women diagnosed with primary breast carcinoma between 1988 and 1997 presenting with a T1-T2 lesion and no metastasis in whom axillary node dissection was performed: 58,070 women were node-negative (N0) and 25,616 were node-positive (N+). End point was death from any cause. Tumor size was modeled as a continuous variable by proportional hazards using a generalized additive models procedure. RESULTS: Functionally, a Gompertzian expression exp(-exp(-(size-15)/10)) provided a good fit to the effect of tumor size (in millimeters) on mortality, irrespective of nodal status. Quantitatively, for tumor size between 3 and 50 mm, the increase of crude cumulative death rate (number of observed deaths divided by the number of patients at risk) increased with size from 10% to 25% for N0 and from 20% to 40% for N+. CONCLUSIONS: The functional relationship of tumor size with mortality is concordant with current knowledge of tumor growth. However, its qualitative and quantitative independence of nodal status is in contradiction with the prevailing concept of sequential disease progression from primary tumor to regional nodes. This argues against the perception that nodal metastases are caused by the primary tumor.

PURPOSE: Recent evidence from our laboratory suggests that the factors of tumor site, patient gender, microsatellite instability, and TP53 mutations are important determinants in the survival benefit associated with adjuvant chemotherapy in Stage III colorectal carcinoma. In the present study we investigated whether these factors, as well as Ki-ras mutations, were also associated with the extent of nodal involvement in Stage III cancers. METHODS: Nodal involvement was retrospectively evaluated in a series of 645 patients with Stage III colorectal cancer from Sir Charles Gairdner Hospital. The number of involved nodes was correlated with the clinicopathologic features of gender, age, tumor site, and histologic grade, as well as to the genetic alterations of TP53 mutation, Ki-ras mutation, and microsatellite instability. RESULTS: The median number of nodes examined per tumor was 11 (range, 1–53). Forty-nine percent of cases had one or two involved nodes and 51 percent had three or more involved nodes, the latter feature being associated with significantly reduced patient survival. No differences in the extent of nodal involvement were apparent with respect to tumor site, patient gender, or TP53 or Ki-ras mutation status. Tumors from younger patients (P = 0.025) or with poorly differentiated histology (P = 0.007), were associated with significantly higher nodal burden, whereas the microsatellite instability phenotype was associated with less extensive nodal involvement (P = 0.020). Survival benefits from the use of chemotherapy were apparent for both the low and high nodal involvement groups, although the latter seemed to obtain relatively more benefit. Multivariate analysis of patients treated with chemotherapy found that gender, grade, and microsatellite instability, but not nodal involvement, were independently prognostic for survival. CONCLUSION: The extent of nodal involvement in Stage III colorectal cancer is related to patient age, tumor grade, and microsatellite instability status, but not to tumor site, patient gender, TP53 or Ki-ras mutation. These results indicate that differences in metastatic nodal burden cannot explain previously observed site, gender, and TP53 mutation differences in the response to chemotherapy.