The Stockholm breast cancer screening trial — 5-year results and stage at discovery

In screening programmes it is important to assess a preliminary effectiveness of the screening method as soon as possible in order to forecast survival figures. In March 1981 a controlled single-view mammographic screening trial for breast cancer was started in the south of Stockholm. The population invited for screening mammography consisted of 40,000 women aged 40–64 years, and 20,000 women served as a well-defined control group. The main aim of the trial was to determine whether repeated mammographic screening could reduce the mortality in the study population (SP) compared to the control population (CP).The cumulative number of advanced mammary carcinomas in the screening and the control populations from the first five years of screening have shown a tendency towards more favourable stages in the screened population aged 40–64 years. A breakdown by age suggests an effect in age group 50–59 years, but not yet in age groups 40–49 and 60–64 years.When comparing the rates of stage II+ cancer, an increased number is found in the study group. As the total rate of breast cancer is higher in SP than in CP, there ought to be a concealed group of stage II+ cancers in the CP which makes the comparison biased. A new approach has been designed, where an estimation of the hidden number of stage II+ cancers in CP is added to the clinically detected cases, and in this respect a comparison has shown a decrease in the cumulative number of advanced cancers in the SP in relation to the CP (p<0.05). According to this it could be important to add the estimated number of undetected, hidden cases in the control group in order to utilize the difference in detection rate in the screening- and control group respectively.     

Randomized trial of adjuvant tamoxifen combined with postoperative radiation therapy or adjuvant chemotherapy in postmenopausal breast cancer

From 1976 to 1984, 427 postmenopausal women with high-risk breast cancer (pN + or pT greater than 30 mm) were randomized between postoperative radiation therapy (RT), radiation therapy plus tamoxifen (RT-TAM), adjuvant chemotherapy (CT), or chemotherapy plus tamoxifen (CT-TAM). Surgery was a modified radical mastectomy in all cases. The radiation therapy was given with high-voltage techniques and included the chest wall and regional nodes. The dose was 4600 cGy/4 1/2 weeks. Tamoxifen was given at a dose of 40 mg daily for 2 years. The adjuvant chemotherapy consisted of 12 cycles of cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) (or chlorambucil, methotrexate, and 5-fluorouracil [LMF] for patients entered before 1978). At a median follow-up time of 6 1/2 years the recurrence-free survival was significantly better for patients allocated to radiation therapy compared to chemotherapy and for patients allocated to tamoxifen compared to no adjuvant endocrine treatment (P less than 0.01). At 10 years the recurrence-free survival for patients in the RT-TAM, RT, CT-TAM, and CT groups was 63%, 57%, 47%, and 31%, respectively. A significant reduction of treatment failures with tamoxifen was only observed among patients with estrogen receptor-positive tumors. The overall survival difference in favor of patients allocated to radiation therapy or tamoxifen was not significant: the respective survival percentage at 10 years in the RT-TAM, RT, CT-TAM, and CT group was 65%, 62%, 52%, and 50%. The results indicate that postoperative radiation therapy continues to play an important role in the primary management of postmenopausal women with high-risk breast cancer and that the addition of tamoxifen may further improve the results among ER-positive patients.     

Assessment of malignancy potential in so-called interval mammary carcinomas

Forty-two so-called interval cancers of the breast were studied. The mammograms were reviewed and the tumors were classified as 14 'unrecognized', 9 'observer error', 1 'technical error' and 18 'true' interval cancers. By using a scoring system based upon histologic differentiation, axillary nodal status, estrogen receptor level, and nuclear DNA content, eight ductal carcinomas with high malignancy potential were identified. All of these tumors belonged to the group 'true' interval cancer. The data indicate that the mammographic subgroup 'true' interval cancer identifies the highly malignant tumors. However, even this strictly selected subgroup is heterogeneous since it also includes some tumors with low malignancy potential.     

The Stockholm trial on adjuvant tamoxifen in early breast cancer

Summary The paper presents interim results of an on-going randomized trial of adjuvant tamoxifen (40 mg daily for 2 years) versus no endocrine adjuvant therapy in postmenopausal women with early breast cancer. A total of 1407 patients were included in the study between November 1976 through June 1984. Estrogen receptor (ER) data were available on 1184 patients (84%). The median follow-up was 53 months. Adjuvant tamoxifen increased the recurrence-free interval (P<0.01) but had no significant effect on overall survival. Treatment failures were reduced by 25% (P<0.01) and deaths by 7% (P>0.05). Tamoxifen mainly decreased the frequency of loco-regional recurrence whereas distant metastases were less affected. The treatment effect was independent of tumor stage but was significantly related to the estrogen receptor (ER) content of the primary tumor. Tamoxifen appeared ineffective among ER negative patients, and the greatest effect was seen among those with high levels of ER. The results indicate that the main mechanism of action of adjuvant tamoxifen is similar to that suggested in advanced disease, i.e. an interaction with the estrogen receptor.     

Beneficial effects of hypertonic saline/dextran on early survival in porcine endotoxin shock

BACKGROUND: Hypertonic saline/dextran (HSD) has been shown to have beneficial effects in haemorrhagic shock. These effects, with improved haemodynamics and organ perfusion, would in theory also be of benefit in septic shock. However, this is less studied. We have therefore further evaluated the effect of additional treatment with HSD in a porcine endotoxin shock model. METHODS: Sixteen anaesthetized pigs were used. A continuous infusion of endotoxin (LPS EC) was increased stepwise during 30 min to a rate of 5 microg/kg/h. The infusion was discontinued after 3 h and the animals were observed for another 2 h. The animals received continuous basal fluid resuscitation with isotonic Ringer's glucose 2.5% at a rate of 20 ml/kg/h throughout the experiment. After 1 h of endotoxin infusion, the animals were randomized to additional treatment with HSD, 4 ml/kg over 5 min, or the same volume of isotonic saline. Every 30 min, haemodynamics and mixed venous saturation (SvO2) were measured via a pulmonary artery catheter. Regional blood flow rates were measured continuously by perivascular ultrasonic flow probes. The metabolic response was measured by arterial blood gas analysis. RESULTS: The endotoxin put all animals into a progressive hypodynamic circulatory shock during the experiment. Treatment with HSD improved survival rate to 8/8 compared with controls 3/8. There was a transient circulatory recovery with improved central and regional haemodynamics, accompanied by stabilized metabolic response. CONCLUSION: Treatment with additional HSD improves survival in an early phase of endotoxin shock. Generally improved haemodynamics and oxygenation of peripheral tissues are suggested as possible mechanisms.     

Randomized study of mammography screening — preliminary report on mortality in the stockholm trial

Summary In March 1981, 40,318 women in Stockholm, aged 40–64, entered a randomized trial of breast cancer screening by single-view mammography alone versus no intervention in a control group of 20,000 women. The attendance rate during the first screening round was 81 per cent and the cancer detection rate was 4.0 per 1000 women. The detection the rate fell to 3.1 per 1000 in the second round, which was completed in October 1985. During 1986 the controlled design of the study was broken and the contro women were invited once to screening which was completed the same year. A total of 428 cases of breast cancer were thus diagnosed in the study group and 439 in the adjusted control group. After a mean follow-up of 7.4 years the number of breast cancer deaths in the study and control groups was 39 and 30 respectively. The relative risk of breast cancer death (screening versus control) was 0.71 (95 per cent confidence interval: 0.4–1.2). Among women older than 50 years at entry the relative risk was 0.57 (95 per cent confidence interval: 0.3–1.1). Cancer deaths among women under 50 were few and perhaps because of this no mortality reduction was seen in this age group. The estimate of mortality reduction lies between the results from two earlier Swedish randomized controlled trials.     

Pyogenic liver abscess as a cause of acute upper abdominal pain. A report of two cases.

The clinical course of 2 patients with acute abdominal pain, which was eventually found to be due to pyogenic hepatic abscesses is described. One patient, operated on late in the course, died; the other, who was operated on early, recovered. The importance of considering this life-threatening disease in the differential diagnosis of acute abdominal pain is emphasized.     

Analysis of interval breast carcinomas in a randomized screening trial in Stockholm

In the interval between screening examinations, some cases of breast cancer are invariably detected clinically in patients whose mammogram was considered to be normal at the earlier screening. During the first interval in the Stockholm study, 60 interval cancers were detected, giving a rate of 1.8 cases/1000 examinations/24 months. About half of these interval cases (31/60) were true interval tumours in that no sign of them could be found on the first mammogram; the other half, non-true, were possible to trace on the first mammogram. It is mainly women under 50 who feature in the interval group, above all in the sub-group of true interval cancers (p<0.05).The incidence of interval cancer rises, as expected, with the length of the interval (Fig. 1). In the final six months of the 2-year interval the incidence of interval cancers had risen to 88 per cent of the cancers detected in the control group in the same period of time.The cumulative incidence of interval cancers supports the hypothesis that the distribution of sojourn time in the interval 0–2 years is approximately rectangular. This means that shortening the interval by one-half would halve the number of interval cases.If mammography becomes a wide spread screening method for early detection of breast cancer, the number of non-true interval cancers could be a feed back on the effectiveness of the screening.An analysis of the malignancy of the true interval cancers, based on tumour size, axillary status, tumour stage, and estrogen receptor content, shows that these are the more malignant tumours with an unfavourable prognosis, while the control group is intermediate in this respect and the tumours detected at screening have the most favourable prognosis.     

Relationship Between Certain Radiographic and Biologic Characteristics in Breast Cancer

The relationship between mammographic appearance of micro-calcifications and tumor stage, malignancy grade, estrogen receptor (ER) content and nuclear DNA pattern was studied in 92 mammary carcinomas. The results indicate that no complementary prognostic guidance can be obtained from the radiographic appearance of a tumor apart from a high probability of a spiculated cancer being ER-rich. The finding of a relatively high proportion of aneuploid and ER-poor carcinomas among tumors with microcalcifications indicates that this radiographic characteristic might be associated with increased growth potential.