Prediction of survival in breast cancer: evaluation of different multivariate models.

BACKGROUND: We compared the performance of multivariate models based on mitotic activity index, lymph node status, and tumor size in the prognostication of breast cancer. MATERIAL AND METHODS: Cox and discriminant models for survival were created for two patient groups: a) 120 breast cancer patients, and b) 86 patients with ductal infiltrating carcinoma. The models were compared with the model of Baak et al (1985). RESULTS: The models distinguished between dying and surviving patients with an efficiency of 70.9-77.9% in mutual tests. With a single cutoff the model of Baak et al was less efficient (50.8-65.8%). If a region of uncertainty was allowed between two cutpoints, the efficiencies below and above the cutpoints increased. When the uncertain region included a third of the patients, the efficiency varied between 73.8 and 84.7%. CONCLUSION: Multivariate models seem to need a region of uncertainty between two discriminating cutpoints. These models resulted in the correct prediction of prognosis in about 75% and more of patients. With different materials the models differed in efficiency. With a region of uncertainty the model of Baak et al performed well with completely independent material.

Prognostic studies in breast cancer. Multivariate combination of nodal status, proliferation index, tumor size, and DNA ploidy.

We studied histological samples and clinical data from 111 breast carcinoma patients originally treated in 1975-1977 who did not have distant metastases at the time of diagnosis. A multivariate survival analysis using the Cox model selected the studied variables in the following order according to their prognostic association (breast cancer deaths, or deaths from any cause): axillary lymph node status, tumor size, mitotic index, and DNA ploidy status. The association of the different variables to the prognosis in respect to breast cancer deaths was evaluated 1-10 years after treatment by stepwise logistic regression. Lymph node status, tumor size, mitotic index, and DNA ploidy all showed significant relation to the prognosis but this association varied considerably with time of observation.

Immunohistochemical demonstration of c-erb B-2 oncoprotein expression in female breast cancer and its prognostic significance.

The expression of c-erb B-2 oncoprotein was studied immunohistochemically in paraffin embedded biopsy specimens of 91 female breast carcinomas. The mean (+/- SD) age of the patients at diagnosis was 59.0 (+/- 13.2) years and they were prospectively followed-up for a mean of 12.4 years (range 11.5-13.3 years). The c-erb B-2 expression was analysed in relation to clinical stage, menopausal status, histological grade, tubular growth pattern, irregularity of nuclei, DNA ploidy and clinical outcome during the follow-up. Grade III tumours showed higher c-erb B-2 expression than low grade tumours and the c-erb B-2 expression than low grade tumours and the c-erb B-2 positivity was also related to the irregularity of the nuclei (p = 0.0815). Crude survival (p = 0.0635) and breast cancer survival (p = 0.072) could be predicted by c-erb B-2 expression, in that the c-erb B-2 negative tumours survived longer. The prediction of crude survival (p = 0.03), breast cancer survival (p = 0.04) and disease-free survival (p = 0.037) was more reliable in postmenopausal women. The results suggest that c-erb B-2 oncogene expression can be used as a prognostic parameter in predicting the biological behaviour of female breast cancer.

An improved prognostic index of axillary node involvement in breast cancer incorporating DNA ploidy and tumour size.

A multivariate prognostic index based on clinical data and the results of flow cytometry for the grading of breast cancer was evaluated in 117 patients whose disease had been detected and treated by mastectomy with axillary clearance between 1974 and 1976. Survival analysis with Cox's regression model pointed to three important prognostic factors: lymph node involvement (p less than 0.001), DNA ploidy (p less than 0.01) and tumour size (p less than 0.01). These factors were incorporated into a prognostic index, in which the lymph node involvement, DNA ploidy, and tumour size contributed to the index in that order. Logistic discriminant analysis with five year follow-up as the fixed end point (70 alive, 47 dead) gave the same result; lymph node involvement, tumour size, and DNA ploidy were the best prognostic indicators of survival. The result showed that our multivariate prognostic index was more powerful than lymph node involvement alone. The use of this prognostic index is recommended for selecting patients for different treatments.

Relationship between DNA ploidy and survival in patients with primary breast cancer.

The DNA ploidy of breast cancer tissue from paraffin blocks was measured by flow cytometry in 117 patients whose disease had been detected and treated with surgery between 1974 and 1976. Patients with aneuploid tumours had positive axillary nodes and distant metastases more often than those with diploid tumours. Aneuploid tumours were more common in postmenopausal than premenopausal women. The S-phase fraction (SPF) was significantly higher in aneuploid than in diploid tumours and positive axillary lymph nodes were found in 26 per cent of the patients who had a tumour with a SPF below the median (4.8 per cent) and in 48 per cent of those with tumours with SPF values above the median. At the primary clinical investigation 2 per cent of the patients with diploid tumours and 6 per cent of those with aneuploid tumours had distant metastases. During the follow-up, the proportion of patients with distant metastases increased to 42 and 72 per cent, respectively. With a follow-up of 11.5 years, the DNA aneuploidy of the tumour showed a significant association with decreased survival. Thirty-three per cent of patients with diploid and 65 per cent of patients with aneuploid tumours had died from breast cancer during the follow-up (P less than 0.001). All patients with hypertetraploid or multiploid tumours died from breast cancer. High SPF values were associated more closely with distant metastases or death during the follow-up than low SPF values. Our results suggest that DNA ploidy measured by flow cytometry from paraffin embedded tissue blocks of human breast cancer can be used to predict the aggressiveness of the tumour and the survival of the patients.

Lymphoma of the breast.

Three cases of malignant lymphoma of the breast are described, seen over a 14 year period in the district of Kuopio University Central Hospital. The neoplasms were either of high or intermediate grade of malignancy: one immunoblastic, one Burkitt-type, and one centroblastic-centrocytic malignant lymphoma. The patient with centroblastic-centrocytic malignant lymphoma had advanced disease with pulmonary and adenoidal involvement and died 15 months after the detection of the breast tumor. The two other neoplasms were confined to the breast with no evidence of further dissemination. The patient with immunoblastic malignant lymphoma developed intestinal lymphoma 3 years later which was treated with surgery and cytostatic therapy. The patient has since been in remission for a period of 10.5 years. The patient with Burkitt-type malignant lymphoma was subjected to surgical resection which was followed by cytostatic treatment. The patient has remained in good health during the 20-month follow-up. The correct diagnosis is especially important in breast lymphoma because without it the appropriate treatment cannot be applied.

Melorheostosis. A case report with special reference to bone mineral density, bone circulation and bone scan.

A new case of melorheostosis is presented. Bone mineral density, and bone circulation were determined and bone scan carried out in the patient. The bone mineral density measured by photon absorption in the region of the distal radius of the patient's left forearm was found to be within normal limits, the bone blood circulation determined by Xc-133 clearance method was better in the affected side, and an area of increased uptake of Tc99m was found by bone scanning in the affected extremity.