Pattern of spread and progression in relation to the characteristics of the primary tumour in human breast cancer.

Characteristics of primary breast tumours were related to the extent of dissemination, the anatomical location of metastases, and the rate of progression in 863 patients with recurrent breast cancer. The following features were examined: tumour laterality, location within the breast, size, invasion of skin or fascia, presence of residual cancer tissue (RCT) in the mastectomy specimen, and number of positive lymph nodes. Increasing tumour size, increasing number of nodes, and the presence of local invasion and RCT were all associated with a short duration of survival both from initial diagnosis and from first recurrence. None of the factors were related to either the extent of dissemination or the rate of progression. Patients who had their primary tumours located in the medial or central part of the breast had an increased incidence of mediastinal and pleural recurrences respectively. Primary tumours greater than 5 cm, invasion of skin or fascia, and presence of RCT were all associated with an increased incidence of local recurrences. In addition, both RCT and fascial invasion were associated with increased occurrence of brain metastases. Most differences were explainable on the basis of local and regional lymphodynamics. Since the status of the features examined here all vary with time from tumour inception, it is suggested that the impact on prognosis is related to variations in tumour age from inception to primary diagnosis rather than to qualitative biological differences.

Body size and menopausal status in relation to the pattern of spread in recurrent breast cancer.

The prognosis and pattern of spread were related to body size and menopausal status in 863 patients with recurrent breast cancer. These patients were all enrolled in the adjuvant protocols of the Danish Breast Cancer Cooperative Group. The pattern of spread was illustrated by the number of metastases, the anatomical location of recurrence, and the rate of progression. Body size was estimated as height, weight, Quetelet index (QI), and body surface area (BSA). The body size was unassociated with both recurrence-free interval (RFI) and survival after recurrence (SAR). The groups of patients with different body size had both the same number and the same location of metastases. The tumour growth rates were estimated as clinical rates of progression (i.e. the time elapsed from a single distant metastasis until dissemination). The progression rate was unaffected by body size. Postmenopausal patients had a significantly shorter RFI and SAR compared to premenopausal patients. The number of metastatic sites, the anatomical location of metastases, and the rate of progression were similar in pre- and postmenopausal patients. The study could not confirm most findings from the literature which report a poor prognosis for patients with large body size. Moreover, the results do not suggest interactions between body size, menopausal status, and the clinical course of recurrent breast cancer.

Histological grade and steroid receptor content of primary breast cancer--impact on prognosis and possible modes of action.

The clinical course of breast cancer was related to degree of anaplasia (DA) and steroid receptor (SR) content of primary tumours in 743 patients (pts) with clinical recurrence, initially enrolled in the DBCG-77 protocols. The oestrogen receptor (ER) and the progesterone receptor (PgR) content was known in 110 and 67 pts. The recurrence-free interval, survival after recurrence, and the overall survival were all prolonged in patients with well differentiated tumours or with high SR content. The tumour growth rates were estimated as clinical rates of progression (i.e., the time elapsed from a single distant metastasis until dissemination). The progression rate was prolonged in relatively well differentiated as well as in receptor rich tumours. The extent of dissemination, as indicated by the number of metastatic sites, was not associated with either DA or SR content. However, the anatomical distribution of metastases varied with both DA and SR content: signs of poor prognosis (high DA or low SR content) were associated with occurrence of visceral metastases. In contrast, SR rich tumours had a propensity for recurrence in bone. The results suggest that the impact on prognosis of the features examined here includes both variations in growth rate and metastatic pattern.

Adjuvant systemic treatment and the pattern of recurrences in patients with breast cancer.

The aim was to analyze the impact of adjuvant systemic treatment (AST) on the anatomical distribution, the number, and the temporal relationship of the first metastases in 635 patients (pts) with breast cancer. These patients participated in the prospective studies of AST of the Danish Breast Cancer Cooperative Group (DBCG) 77-program. All patients had primary high-risk breast cancer (i.e. node positive or local invasion or tumor size greater than 5 cm). The initial treatment was mastectomy with axillary sampling, followed by postoperative radiotherapy. The types of AST and the number of patients with recurrence were: chemotherapy (CT), 134 pts; levamisole (LEV), 96 pts; tamoxifen (TAM), 154 pts. The pattern of recurrence in these patients was compared with the pattern of recurrence in 251 pts who did not receive AST (controls). Although CT reduced the total number of metastatic sites (P = 0.04), the incidence of liver metastases was increased compared to untreated controls (P = 0.02). The median number of metastatic sites was equal in TAM- and LEV-treated pts compared to controls. The incidence of lung metastases was increased in TAM-treated pts (P = 0.03), and LEV-treated pts had a decreased incidence of lymph node (P = 0.01) and pleural recurrences (P = 0.01) compared to controls. The results may suggest that mechanisms of clonal selection during the metastatic process involve differences in sensitivity to antineoplastic treatments of metastases at various anatomical locations.

The pattern of metastases in human breast cancer. Influence of systemic adjuvant therapy and impact on survival.

Of the 3,802 patients enrolled in the DBCG 77 protocols, 863 developed clinical recurrence within a median follow-up time of 4.9 years (range 2.0-7.0). More than 69% of these had their first recurrence confined to a single anatomical site and 12% had more than two metastatic sites. The most common sites were bone (35%), lung (23%), skin (22%), and regional lymph nodes (16%). The observation period after first recurrence was 3.6 years (range 0.8-6.4). Survival after recurrence was significantly related both to the location and the number of metastases. Patients who were given adjuvant chemotherapy (n = 134) had significantly fewer metastatic sites and significantly more frequent liver metastases than untreated patients (n = 50). Patients who received adjuvant tamoxifen (n = 154) had the same number of metastatic sites, but more often had lung metastases than untreated patients (n = 201). These results probably reflect that metastases in different anatomical locations differ with respect to sensitivity to antineoplastic treatments.

Stage and pattern of metastases in patients with breast cancer.

This study compares the pattern of metastases in 228 patients with initial stage I and 635 patients with initial stage II breast cancer. All these patients had recurrence within a median time of follow-up of 4.9 years (range 2.0-7.0 years). All patients were initially mastectomized, and staging was based on histopathological evaluation of mastectomy specimens. Patients with stage II disease received postoperative radiotherapy; 67% also received systemic adjuvant therapy. Locoregional recurrences were the most common sites of recurrence in stage I, whereas distant metastases occurred more often in stage II patients. Stage II patients had a significantly higher number of metastatic sites than stage I patients. Among patients with a single site of recurrence the frequency of local or regional recurrence was 62% in stage I patients compared to 16% in stage II patients. When correcting for this difference, which was ascribed to the effect of radiotherapy, the number and the distribution of metastatic sites were almost equal in stage I and II patients. The anatomical distribution of metastatic sites in different periods after mastectomy was almost the same in stage I and stage II patients; extraregional lymph node metastases, however, occurred earlier in stage II than in stage I patients. The recurrence-free interval, the survival after recurrence (SAR), and the overall survival were all significantly shorter for stage II than for stage I patients. The reduced SAR for patients with stage II disease hints that tumours of higher stages have a higher rate of progression. The progression time, however, was of the same duration in patients with initial stage I and II breast cancer. The prognostic significance of the classification of patients with breast cancer according to stage does not seem to discriminate tumours with different biological properties with regard to the rate as well as the pattern of dissemination. Postmastectomy follow-up of patients with stage I and II disease should therefore, follow the same guide-lines. Since the anatomical distribution of metastases was the same in different periods after mastectomy, the screening for recurrent disease should not be directed towards any specific sites in certain periods after initial diagnosis.

Prevalence and mortality of acute myocardial infarction in patients with diabetes.

The purpose of this study was to investigate if insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM) predispose to the development of acute myocardial infarction (AMI) and modify the prognosis. The study includes 832 AMI patients consecutively hospitalized over a 3-yr period. The prevalence of diabetes mellitus among the AMI patients was 9.7% and is significantly higher than in an age-matched population, where it is 6.1% (P less than 0.001). The prevalence of diabetes was higher for women than for men (14.9% versus 7.6%). The risk of AMI was found to be twice as high among IDDM than among nondiabetic patients (P less than 0.001). Men with NIDDM were not found to have a significantly higher risk of AMI (P greater than 0.1), but the risk of AMI in women with NIDDM was approximately doubled (P less than 0.01). During the first month following AMI the mortality rate for nondiabetic patients was 20.2% compared with 42.0% for diabetic patients (P less than 0.001). Insulin treatment in NIDDM was associated with a reduced mortality rate compared with treatment with oral agents (P less than 0.05). The mortality rate was significantly higher in patients with poor metabolic control compared with patients in good control, whether before AMI or at the time of hospitalization. Diabetic patients had a higher risk of developing cardiogenic shock and conduction disorders than nondiabetic patients. We conclude that diabetes mellitus disposes to AMI and that the mortality rate of AMI is significantly increased among diabetic patients. Poor metabolic regulation of the diabetes may aggravate the prognosis for AMI.

Oestrogen receptor assay. False positive analysis?

The influence of unlabelled oestradiol, DES, testosterone and R-5020/org 2058 on tritiated oestradiol binding was investigated in 162 ER positive cases of patients with primary breast carcinoma. A dextran-coated charcoal as well as a sucrose gradient method was applied. In 122 cases only unlabelled oestradiol and DES significantly displaced the binding of labelled oestradiol. In the remaining 40 cases, oestradiol, DES, as well as testosterone and R-5020/org 2058 were able to displace the high-affinity, saturable binding of tritiated oestradiol equally. Possible explanations of this new discovery are discussed.