Overview of randomized trials of postoperative adjuvant radiotherapy in breast cancer.
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Breast Neoplasms↗
Biomedical subjects
R Peto
Publications and source records attributed to R Peto.
Serum vitamin E and risk of cancer among Finnish men during a 10-year follow-up.
The association between serum alpha-tocopherol levels and the subsequent incidence of cancer was investigated in a longitudinal study of 21,172 men initially aged 15-99 years in six geographic areas in Finland. The baseline examination was conducted in 1968-1972, and during the follow-up of 6-10 years, 453 cancers were diagnosed. The serum alpha-tocopherol levels were measured from stored serum samples from these men and from 841 male controls, matched for municipality and age, who did not develop cancer during the follow-up. The mean levels of serum alpha-tocopherol among the cancer cases and controls were 8.02 and 8.28 mg/liter, respectively. A high serum alpha-tocopherol level was associated with a reduced risk of cancer. The relative risk of cancer in persons in the two highest (threshold 8.70 mg/liter) quintiles of serum alpha-tocopherol was 0.64 (95 per cent confidence interval = 0.49-0.85) in comparison with those in the three lowest quintiles. The association was strongest for the combined group of cancers unrelated to smoking and varied between subgroups of the study population as well as between different cancers. The association persisted when adjusted for serum cholesterol, serum vitamin A, serum selenium, and various confounding factors. It also persisted when subjects with possible signs of cancer at the time when the blood samples were drawn or with cancers diagnosed during the first two years of follow-up were excluded. These findings agree with the hypothesis that high vitamin E intake protects against cancer.
Adolescent↗
Antiplatelet agents in stroke prevention.
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Cerebrovascular Disorders↗
Tobacco-related deaths in China.
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Adult↗
A prospective cohort study of postmenopausal hormone use and risk of breast cancer in US women.
The association between history of postmenopausal hormone use as of 1976 and breast cancer incidence during 1976-1980 was examined prospectively among 33,335 married, postmenopausal registered nurses aged 30-55 years at entry. Half the women reported postmenopausal hormone use, and one fourth had taken these drugs for over five years. During 1976-1980, 221 new cases of breast cancer were identified. The relative risk (RR) for those who had used postmenopausal hormones when compared with women who had never used them was 1.1 (95% confidence limits (CL) 0.8, 1.4); for current and past users, the relative risks were 1.0 (95% CL 0.7, 1.4) and 1.3 (95% CL 0.9, 1.8), respectively. These ratios were not substantially modified by whether or not a woman's ovaries had been removed or by other known breast cancer risk factors. No increase in breast cancer risk was apparent among women who had used postmenopausal hormones for less than five years (RR = 1.0, 95% CL 0.5, 1.6). An apparent effect among the subgroup of women who had used them for five to nine years (RR = 1.5, 95% CL 1.0, 2.2) was not present among the few women with longer-term use (RR = 0.9, 95% CL 0.4, 1.6). These findings are moderately reassuring, but since there are as yet few women in this cohort with long-term durations of use and, particularly, with long intervals since first use, continued follow-up of this and other cohorts will be required before firm conclusions can be drawn, especially among specific subgroups.
Adult↗
Ranking the potential carcinogenic hazards to workers from exposures to chemicals that are tumorigenic in rodents.
For 41 chemicals there exist both reasonable data on carcinogenic potency in experimental animals and also a defined Permissible Exposure Level (PEL), which is the upper limit of legally permissible chronic occupational exposure for U.S. workers. These 41 agents are ranked by an index that compares the permitted chronic human exposure to the chronic dose rate that induces tumors in 50% of laboratory animals. This index, the Permitted Exposure/Rodent Potency index, or PERP, does not estimate absolute risks directly, but rather suggests the relative hazards that such substances may pose. The PERP values for these 41 substances differ by more than 100,000-fold from each other. The PERP does not take into account the actual level of exposure or the number of exposed workers. Nevertheless, it might be reasonable to give priority attention to the reduction of allowable worker exposures to substances that appear most hazardous by this index and that some workers may be exposed to full-time near the PEL. Ranked by PERP, these chemicals are: ethylene dibromide, ethylene dichloride, 1,3-butadiene, tetrachloroethylene, propylene oxide, chloroform, formaldehyde, methylene chloride, dioxane, and benzene.
Animals↗
Overview of randomized trials of postoperative adjuvant radiotherapy in breast cancer.
An overview of the mortality results of the mature trials in which radiotherapy was a randomized option after simple or radical mastectomy is presented. The principal aim of the overview was to study long-term survival, and recent trials, often including chemotherapy options, have not been included. A total of 7941 patients were entered into these trials and 4148 deaths occurred. No differences were found in survival in the first 10 years of follow-up, in trials employing either radical mastectomy or simple mastectomy. Follow-up information after 10 years came mostly from trials employing radical mastectomy with or without irradiation, and in these trials a significant excess of deaths was observed among patients given radiotherapy (P less than 0.001, all trials; P = 0.002, radical mastectomy trials only). Further data collection will be necessary to determine which causes of death are elevated.
Breast Neoplasms↗
Overview of randomized trials comparing radical mastectomy without radiotherapy against simple mastectomy with radiotherapy in breast cancer.
An overview of mortality in the mature randomized trials comparing radical mastectomy without radiotherapy against simple mastectomy with radiotherapy has been conducted. These trials mark a transitional period between radical mastectomy and simple mastectomy as the generally preferred surgical treatment and as such are not strictly trials assessing the value of postoperative adjuvant radiotherapy. All known mature trials have been included and these four trials have entered a total of 3236 patients, in whom 1678 deaths have been recorded. Overall, no significant difference in survival was seen, but there was a nonsignificant trend for patients given radiotherapy to do worse after 15 years of follow-up.
Breast Neoplasms↗
A correlation study on urinary excretion of N-nitroso compounds and cancer mortality in China: interim results.
Samples of 12-h overnight urine were collected from approximately 40 male adults in each of the 26 counties of China. Two urine specimens were collected from each subject--one after a loading dose of proline and ascorbic acid and another after a loading dose of proline only. Levels of N-nitrosamino acids, nitrite and nitrate were measured in urine samples and correlated with cancer mortality per 100,000 male subjects in the truncated age range 35-64 years. Preliminary results show no clear correlation between presence of stomach cancer or liver cancer and nitrosation potential [as measured by the urinary level of N-nitrosoproline (NPRO) after the proline load test or of nitrate]. There was a moderate, although not clearly significant, tendency for oesophageal cancer mortality rates to be associated positively with nitrosation potential and negatively with background ascorbate levels in plasma. This result was due chiefly to the inclusion of one county (Song Xian) in which there is a fairly high oesophageal mortality rate, an average nitrosation potential three times greater than that of any other county, and the lowest ascorbate index of any county. Further study of this county is planned.
Adult↗
Is a controlled trial of long-term oral anticoagulants in patients with stroke and non-rheumatic atrial fibrillation worthwhile?
A controlled randomised trial large enough to assess the value of anticoagulating stroke patients in atrial fibrillation would be difficult to conduct in the UK and the results would be applicable to only a small proportion of stroke patients. It would be more worthwhile to organise a trial that also assessed the value of other treatments that are simpler and applicable to all stroke patients. A trial that assessed the value of aspirin and beta-blockers against control in all stroke patients would not cost much more than one restricted to comparing anticoagulants against control in patients with stroke and atrial fibrillation but would provide information of more relevance to the management of patients with stroke in the UK.
Administration, Oral↗
Oral contraceptives and breast cancer. A prospective cohort study.
In 1976, information on oral contraceptive (OC) use as well as numerous risk factors for breast cancer was provided by 121,964 married female registered nurses aged 30 to 55 years. Ninety-two percent of women in the cohort completed follow-up questionnaires, and vital records were systematically searched to ascertain deaths among nonrespondents. After four years of follow-up, 592 incident cases of breast cancer were identified. Compared with never users, the age-adjusted relative risk (RR) of breast cancer, regardless of menopausal status, among all women who had ever used OCs was 1.0. Among premenopausal women compared with those who had never used OCs, the RR of breast cancer was 1.5 for current use of OCs in 1976 and 1.0 for past use. Among postmenopausal women, the RR for past use of OCs was 1.0. These estimates were essentially unaltered after controlling for other known risk factors for breast cancer in multiple logistic regression analysis. Furthermore, there was no modification of these effects by family history of breast cancer, age at first use, timing of the first birth, or other breast cancer risk factors. Data on past use of OCs provide substantial reassuring evidence that there is no large excess risk of breast cancer within a few years of cessation of pill use. The observed moderate elevation of breast cancer risk with current use was of borderline statistical significance. However, the observation was based on 29 cases and may reflect the effect of sampling variability, as most other studies have not observed a relationship between current use of OCs and breast cancer in women of this age.
Adult↗
Overview of cancer time-trend studies in relation to changes in cigarette manufacture.
The chief purpose of the present chapter is not to review lung cancer trends in general, but merely to consider the extent to which trends in national lung cancer rates can help assess any differences between the carcinogenic effects of different types of cigarette. For this limited purpose, the British data are uniquely informative, for British male lung cancer rates were already high but stable before the cigarette tar levels were halved, and British male cigarette consumption remained stable for some years thereafter. Against this apparently stable background, an otherwise unexplained decrease of about one-half in British male lung cancer mortality in early middle age has followed the decrease in cigarette tar deliveries, which is consistent with Stellman's conclusion (this volume), based on review of the case-control and prospective studies, that cigarette-induced lung cancer risks are approximately proportional to machine-measured tar deliveries. Lung cancer trends are also reviewed for males from the USA (where cigarette tar deliveries have been greatly reduced) and from the USSR (where they have not).
Adult↗
Influence of dose and duration of smoking on lung cancer rates.
Lung cancer risks depend far more strongly on the duration than on the daily dose-rate of cigarette smoking. For example, a three-fold increase in the daily dose-rate may produce only about a three-fold increase in effect, while a three-fold increase in duration might produce about a 100-fold increase in effect. Hence, a few decades after cigarette smoking becomes widespread, national lung cancer rates may remain very misleadingly low, even though they will eventually become extremely high.
Age Factors↗
Antihypertensive treatment in pregnancy.
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Female↗
Overview of randomised trials of diuretics in pregnancy.
Over the past 20 years at least 11 randomised trials of the prevention with diuretics of pre-eclampsia and its sequelae have been undertaken. Nine of these were reviewed. Reliable data from the remaining two were not available. The nine reviewed had investigated a total of nearly 7000 people. Significant evidence of prevention of "pre-eclampsia" was overwhelming, even when oedema was not included as a diagnostic criterion. But as the definitions of pre-eclampsia that had been used depended heavily on increases in blood pressure this evidence may simply have reflected the well known ability of diuretics to reduce blood pressure. When the data on perinatal death were reviewed a little difference was seen in postnatal survival. The incidence of stillbirths was reduced by about one third with treatment, but, perhaps owing to small numbers (only 37 stillbirths), the difference was not significant. Thus these randomised trials failed to provide reliable evidence of either the presence or the absence of any worthwhile effects of treatment with diuretics on perinatal mortality. The implications of this for current and future trials of beta blockers and other agents in the prevention of pre-eclampsia and its sequelae are that extremely large, ultra simple randomised trials are needed, of a size sufficient to permit direct assessment of the effects of treatment not on pre-eclampsia but on perinatal mortality itself. This may require the study of tens of thousands of pregnancies.
Blood Pressure↗
Control of tobacco-related disease.
As ways of discouraging tobacco consumption, the effects of increases in price and in quantitative information may have been under-emphasized. To decrease the hazards of tobacco, switches from cigarettes to pipes, cigars or 'smokeless' tobacco may be useful, as may a reduction in cigarette tar delivery. Indeed, the spread of existing tar level reductions from capitalist to socialist countries might prevent tens of thousands of lung cancer deaths each year in the early decades of the next century, and (perhaps by attempts to engineer cigarettes so that smokers of lower tar cigarettes are less likely to 'compensate' by taking more smoke) it should eventually also be possible to change cigarettes so as also to reduce their effects on heart and lung disease. Changes in consumption and in composition of tobacco products are complementary, not competing, strategies. If both are pursued effectively, then although the life expectancy of old people may not be much improved, the proportion of adults who die before reaching old age will decrease substantially.
Adult↗