14 years of follow-up from the Edinburgh randomised trial of breast-cancer screening.

BACKGROUND: The Edinburgh randomised trial of breast-cancer screening recruited women aged 45-64 years from 1978 to 1981 (cohort 1), and those aged 45-49 years during 1982-85 (cohorts 2 and 3). Results based on 14 years of follow-up and 270,000 woman-years of observation are reported. METHODS: Breast-cancer mortality rates in the intervention group (28,628 women offered screening) were compared with those in the control group (26,026) with adjustment for socioeconomic status (SES) of general medical practices. Rate ratios were derived by means of logistic regression for the total trial population and for women first offered screening while younger than 50 years. Analyses were by intention to treat. FINDINGS: Initial unadjusted results showed a difference of just 13% in breast-cancer mortality rates between the intervention and control groups (156 deaths [5.18 per 10,000] vs 167 [6.04 per 10,000]; rate ratio 0.87 [95% CI 0.70-1.06]), but the results were influenced by differences in SES by trial group. After adjustment for SES, the rate ratio was 0.79 (95% CI 0.60-1.02). When deaths after diagnosis more than 3 years after the end of the study were censored the rate ratio became 0.71 (0.53-0.95). There was no evidence of heterogeneity by age at entry and no evidence that younger entrants had smaller or delayed benefit (rate ratio 0.70 [0.41-1.20]). No breast-cancer mortality benefit was observed for women whose breast cancers were diagnosed when they were younger than 50 years. Other-cause mortality rates did not differ by trial group when adjusted for SES. INTERPRETATION: Our findings confirm results from randomised trials in Sweden and the USA that screening for breast cancer lowers breast-cancer mortality. Similar results are reported by the UK geographical comparison, UK Trial of Early Detection of Breast Cancer. The results for younger women suggest benefit from introduction of screening before 50 years of age.

The Edinburgh randomised trial of breast cancer screening: results after 10 years of follow-up.

The Edinburgh Randomised Trial of Breast Cancer Screening recruited 44,288 women aged 45-64 years into the initial cohort of the trial during 1978-81, and 10 years of follow-up is now complete. A total of 22,944 women were randomised into the study group and were offered screening for 7 years; the remaining women formed the control group. After 10 years, breast cancer mortality is 14-21% lower in the study group than in the controls depending on the precise definition of the end point. These differences are not statistically significant; for breast cancer as the underlying cause of death the relative risk is 0.82 (95% confidence interval 0.61-1.11). Rates of locally advanced and metastatic cancer were substantially lower in the study group, but screening has failed to achieve marked reductions in rates of small node-positive cancers. Those women who accepted the final invitation to screening have been monitored over the 3 year period prior to their first screen under the UK service screening programme. Interval cases, expressed as a proportion of the control incidence, increased from 12% in the first year to 67% in the third year. The reduction in breast cancer mortality for older women (aged at least 50 years) is the same as that for the total study group for this duration of follow-up. For analyses of breast cancer mortality in younger women updates recruited to the trial from 1982 to 1985 (10,383 women with 6-8 years' follow-up) have been included. The reduction in breast cancer mortality for women aged 45-49 years at entry was 22% (relative risk = 0.78, 95% confidence interval = 0.46-1.31).

The efficacy of double reading mammograms in breast screening.

The effect of double reporting the screening mammograms of 31,146 women attending as part of the UK National Health Service Breast Screening Programme was analysed. Ninety per cent had their mammograms read by two of three experienced radiologists. Overall 1846 (5.9%) women were recalled for further assessment. Two hundred and sixty-one patients (0.8%) underwent surgical intervention resulting in the detection of 191 cancers (6.1/1000 women screened). The benign-to-malignant ratio was 1:3.6 (PPV 73.2%). Of the invasive cancers detected 72% had no histological evidence of axillary lymph node metastases. Twenty-one of the 191 cancers detected (10.4%) were missed by one of the two reporters. Six of these were invasive cancers < or = 1 cm in diameter. Comparison of those lesions detected by both readers to those detected by only one, showed readers were more likely to detect those lesions appearing as an opacity (65% vs 38%), but less likely to detect significant microcalcification (15% vs 33%). The difference between the two groups when taken as a whole, however, failed to reach statistical significance (chi 2 = 6.76, d.f. = 3, P = 0.08). In summary, double reporting resulted in an increase in sensitivity of 10%. However, there was a decrease in specificity of 1.8% with 569 women being recalled unnecessarily for assessment and biopsy of 13 benign lesions. The estimated resultant additional financial cost was 13773 pounds.

National Health Service breast screening programme results for 1991-2.

OBJECTIVES: To report the results of the NHS breast screening programme for the year March 1991 to April 1992. DESIGN: A report of statistics was derived from Körner (K62) returns and from the radiology quality assurance programme. MAIN OUTCOME MEASURES: Detection rates for breast cancer and small (< or = 10 mm diameter) invasive cancer, benign biopsy rates, and recall and acceptance rates. RESULTS: The acceptance rate for screening across the United Kingdom was 71.3%. The referral rate for further investigation was 6.2% (regional 4.3-9.0%). The breast cancer detection rate was 6.2 cancers per 1000 women screened (5.1-9.0) and the detection rate of invasive cancers < or = 10 mm was 1.4/1000 (1.0-2.3). 72% of screening programmes reached the target 70% acceptance rate, and 95% of programmes achieved a recall rate of less than 10%. 75% of programmes had a cancer detection rate of more than 5/1000, but only 32% had a detection rate for invasive cancers < or = 10 mm of more than 1.5/1000. CONCLUSIONS: Overall, the results of the screening programme for the year 1991-2 can be regarded as extremely satisfactory, given the size and complexity of the operation.

Interval cancers and sensitivity in the screening centres of the UK trial of early detection of breast cancer.

The incidence rates of interval cancers following a negative breast screen in two screening centres which offered women aged 45-64 annual screening by mammography and/or clinical examination are examined. Sensitivity of screening is estimated by comparing the incidence rate of interval cancers with that expected in the absence of screening, and the results are compared with those from alternative methods of calculating sensitivity. The incidence rate of cancers diagnosed within 12 months of a negative screen by mammography plus clinical examination was reduced by 70% for women aged 45-54, and 84% for women aged 55+. There is no indication from this that sensitivity in the UK trial was substantially lower than in other studies which have achieved larger reductions in mortality.

Assessment of non-palpable mammographic abnormalities: comparison between screening and symptomatic clinics.

A retrospective study found that a breast screening clinic generated fewer localization biopsies for non-palpable mammographic abnormalities than a symptomatic clinic (3.36 versus 9.89 per 1000 mammograms, respectively) and that a greater proportion of such biopsies were malignant. This study determined the reason for this difference. There were 108 of 304 (35.5 per cent) and 17 of 130 (13.1 per cent) carcinomas in women attending the screening and breast clinics respectively (relative risk 2.72 (95 per cent confidence interval 1.70-4.34)). This difference was regardless of age. The characteristics of the mammographic abnormality, the Wolfe pattern, a family history of breast carcinoma, parity and age at first pregnancy were similar in both groups. Women attending the screening clinic were referred for localization biopsy after assessment by clinicians and radiologists at a joint clinic; there was no joint assessment for patients attending the breast clinic. The same staff attended both clinics, although the proportion of time spent at each varied. This study suggests that all women with a non-palpable mammographic abnormality should be reviewed at a joint assessment clinic before localization biopsy is recommended.

Comparative pathology of breast cancer in a randomised trial of screening.

In the Edinburgh Randomised Breast Screening Project (EBSP) to December 1988 there were 500 cancers in the study population invited to screening and 340 cancers identified in the control population. The size and negative lymph node status characteristics of invasive cancers from the two populations were significantly different (P less than 0.05). The cancers detected by screening were predominantly 'early stage', with 16% noninvasive (PTIS) and 42% invasive stage I (pT1 node negative), whereas cancers were frequently 'late stage' (more than pT2) and inoperable in nonattenders (44%) and controls (36%). Grouped according to customary size ranges of invasive cancers, the proportion of cases lymph node positive differed in those screen detected compared with controls, but the benefit in favour of screen detection was not constant. In comparisons of cancers detected at prevalence and incidence screens, as a test of conformity with screening theory, no significant differences were apparent according to size and lymph node status, yet the characteristics of histological type of cancer discriminated significantly (P less than 0.05). When these same histological characteristics were used to compare survival, the capacity to separate invasive cancers into two groups having good and poor survival probabilities was evident, with a significant improvement for the screen detected poor survival group compared with controls (P less than 0.05).

A mobile breast screening project in Scotland: lessons learned for national screening.

In 1986, a project was undertaken to determine the feasibility and cost of screening for breast cancer, using single oblique view mammography. Screening was offered to women aged between 40 and 65, on an open access basis, to those living in rural areas near Edinburgh. This article reports on: the logistical difficulties encountered; the costs of mobile screening; a comparison of costs when screening from a static centre; and, identifies factors found to influence attendance rates. The lessons learned from the project were incorporated into the planning of the mobile van operating in the South-East of Scotland Screening Programme, part of the National Breast Screening Programme; comparisons, where possible, have been included.

Comparison of temperature profiles (DeVeTherm) and conventional venography in suspected lower limb thrombosis.

In 124 patients admitted with suspected acute deep venous thrombosis, the screening value of a new thermographic scanner, DeVeTherm, was evaluated using conventional venography as a reference. The sensitivity of the scanner was calculated at 92% and the specificity at 25%. The predictive value of positive temperature profiles was 0.48, and that of negative temperature profiles, 0.82. On the basis of these results neither the accuracy nor the potential savings justify using temperature profiles alone as a screening test for this condition.

Outcome of surgery for non-palpable mammographic abnormalities.

Four hundred and ninety-three women underwent 515 localization biopsies for non-palpable mammographic abnormalities. The mammographic abnormality was located with a hooked wire in 509 cases. Specimen radiology was performed on all excised tissue. The mammographic abnormality was visualized in the first piece of tissue excised in 402 (78.1 per cent) cases and complete excision was achieved in 476 (92.4 per cent). A palpable nodule was removed in 38 (7.4 per cent) cases and in 17 (44.7 per cent) was shown to contain a carcinoma. The mammographic abnormality was missed in 14 (2.7 per cent) cases or only partly excised in 13 (2.5 per cent). Overall 144 (28.0 per cent) localization biopsies were malignant. The mammographic abnormality was not visualized on the specimen radiograph more frequently in women aged under 55 years, in women with dense breast (Wolfe grade DM or DY) or in those whose mammographic abnormality contained only microcalcification. The 27 women in whom the mammographic abnormality was not visible on the specimen radiograph underwent repeat mammography 2 months later. Only two women required a further localization biopsy and the mammographic abnormality was recovered in the first piece of tissue excised. Women with a carcinoma underwent mastectomy or wide local excision, and residual carcinoma at the localization biopsy site was found in 64 (44.4 per cent) cases. Oestrogen receptor analysis by ligand binding assay was possible in only 71 (49.3 per cent) carcinomas. If the specimen radiograph does not show the mammographic abnormality within pieces of tissue excised and there is no palpable nodule it may be best to conclude the biopsy. In this series these missed lesions were usually benign. Only rarely is a second localization biopsy required and this is performed without difficulty.

Mammographic screening for breast cancer: recall rates using two views compared with the oblique view alone.

Six thousand and eighty women aged 40 to 64 years were screened for breast cancer by single oblique view mammography and 908 (14.9 per cent) were recalled for further examinations. It was estimated that the use of two-view mammography for initial screening would have resulted in a fall of the number of women recalled to 581 (9.5 per cent). More recently, with better equipment and the routine use of a moving grid, the recall rate at initial singleview screening in women over the age of 50 has fallen to the region of 10 per cent. The place of two-view screening is being evaluated in conjunction with grid films and, should a similar proportional fall in recall rates be gained by the addition of a second view, there may well be a place for two-view screening in this situation too.

Edinburgh trial of screening for breast cancer: mortality at seven years.

Between 1979 and 1981, 45,130 women in Edinburgh aged 45-64 were entered into a randomised trial of breast cancer screening by mammography and clinical examination. The initial attendance rate was 61% but this varied according to age and socioeconomic status and decreased over succeeding years. The cancer detection rate was 6.2 per 1000 women attending at the first visit; the rate fell to around 3 per 1000 in the years when mammography was routinely repeated and to around 1 per 1000 at the intervening visits with clinical examination alone as the screening method. After 7 years of follow-up the mortality reduction achieved was 17% (relative risk = 0.83, 95% CI 0.58-1.18), which was not statistically significant, even when corrected for socioeconomic status. In women aged 50 years and over a mortality reduction of 20% was achieved.

Effect of retrograde aminophylline administration on calcium and phosphate solubility in neonatal total parenteral nutrient solutions.

The effect of retrograde administration of aminophylline injection on calcium and phosphate solubility in neonatal total parenteral nutrient (TPN) solutions was studied. Neonatal TPN solutions containing two amino acids solutions in three concentrations (Travasol 1% and 2% and TrophAmine 2%) were formulated. Calcium and phosphate salts were added to achieve calcium concentrations of 10, 15, 20, 25, 30, or 40 meq/L and phosphorus concentrations of 10, 15, 20, 25, 30, or 40 mmol/L. Samples were inspected visually after 18-24 hours; solutions free of precipitation were then infused through two parallel syringe-pump systems designed to simulate clinical conditions for TPN solution administration to a 1-kg neonate. To one system, a 7.5-mg aminophylline dose was added as a manual retrograde injection; sterile water for injection was added as a manual retrograde injection to the other system. The solutions were inspected throughout a one-hour infusion period for precipitate formation in the i.v. apparatus, and the pH of the effluents was determined. Concurrent aminophylline administration resulted in visible precipitate in all but a few of the solutions tested. The solution containing Travasol 2%, calcium 10 meq/L, and phosphorus 10 mmol/L remained clear, as did the solutions containing TrophAmine 2% and the following concentrations of calcium and phosphorus: calcium 10 meq/L and phosphorus 10, 15, or 20 mmol/L; calcium 15 meq/L and phosphorus 10 or 15 mmol/L; and calcium 20 meq/L and phosphorus 10 or 15 mmol/L. An average increase in pH of 0.63 unit was noted in all solutions.(ABSTRACT TRUNCATED AT 250 WORDS)

Stereotaxic localisation and aspiration cytology of impalpable breast lesions.

As part of a programme of assessment of the 'Sterotix' localisation device, aspiration cytology was carried out on 50 patients with 52 impalpable, mammographically detected breast lesions using the stereotaxic guidance device. This was followed by an open localisation biopsy of the area for confirmation. In 12 patients (23%) the aspirations failed to yield sufficient material for diagnosis. This was frequently due to the poorly cellular nature or very small size of the lesions. Of the remaining 40 patients, 15 were regarded as having both mammographically and cytologically benign changes which were confirmed histologically; they could thus have been spared diagnostic surgery. Ten patients had a diagnosis of malignancy with both investigations, and could have had planned investigation and subsequent definitive surgery. Of the remainder, 14 lesions had a report of malignancy or suspicion of it with either technique and these patients would have come to conventional localisation biopsy. Only one patient was found to have a malignancy, who had cytologically benign and mammographically 'probably benign' disease: this was an invasive lobular carcinoma with a dominant in-situ component and may well have been an incidental finding on biopsy.