Will a breast screening programme change the workload and referral practice of general practitioners?

STUDY OBJECTIVE--The aim of the study was to consider possible changes in the clinical activities of general practitioners whose patients are registered in a breast cancer screening programme. DESIGN--The study was a survey based on completion of forms recording breast consultations carried out by participating general practitioners during a four week period. SETTING--One of three intervention centres and one of three comparison centres in the national trial of early detection of breast cancer was selected. The intervention centre was in Guildford; the comparison centre in Stoke on Trent. PARTICIPANTS--The participants were general practitioners in the selected centres. In Guildford, 64 of 99 general practitioners approached took part (65%); in Stoke on Trent, 81 of 177 took part (46%). The proportion of male and female participants in the two centres was similar. Doctors in Stoke on Trent were older and worked in smaller practices than in Guildford. RESULTS--A comparison of workloads showed that in the screening centre there was less demand for doctor consultations from those in the screened age group, but those excluded from screening made more use of the general practitioners' services. A difference in referral practice was also apparent, with doctors in the screening centre referring more frequently for specialist advice. CONCLUSIONS--The evidence suggests that no significant change in the overall use of general practice resources can be expected with the introduction of national screening, but there may be greater pressure on assessment services.     

Further evidence of benefits of a (non-randomised) breast cancer screening programme: the DOM project.

STUDY OBJECTIVE--The aim was to demonstrate the benefits of breast cancer screening on mortality. DESIGN--The study was an evaluation of a breast cancer screening programme by means of different approaches: (1) a case-control study, breast cancer deaths being the cases; (2) comparing the numbers of breast cancer deaths in screened and unscreened women; (3) comparing breast cancer mortality before and after start of the programme; (4) comparing breast cancer mortality in different large cities; (5) comparing screening activity with mortality reduction. SETTING--The setting was a breast cancer screening programme in the city of Utrecht, the DOM project, for women aged 50-64 years old at intake, birth cohort 1911-1925. The programme started in 1974, and there were five screening rounds up to 1984. Participation rate in the first round was 72% (14,697 women). MAIN RESULTS--(1) Screening was protective against dying from breast cancer, odds ratio 0.52, with a stronger effect in older women and no evidence of confounding; (2) risk ratio of dying from breast cancer for women in the response group was the same as the odds ratio, 0.52; (3) breast cancer death rate after the start of the project was nearly 20% lower than before the project started; after correcting for women who could not have benefited from screening the reduction was 33%; (4) a rise in breast cancer mortality in birth cohort 1911-1925 seen in other large cities without a screening programme due to aging of the cohort was not seen in the city of Utrecht; (5) mortality reduction followed the screening activity with a time lag of approximately 5 years. CONCLUSIONS--Early diagnosis of breast cancer by mammography reduces breast cancer mortality in women 50-64 years old at intake; different approaches to the evaluation of the project give different estimates of the screening effect, making clear that the effect depends on the intensity of the programme.     

Secondary prevention: screening for breast cancer

Screening healthy women in order to detect the earliest signs of breast cancer may offer a possibility of curing many breast cancer patients who would be incurable if left until they developed symptoms. However, the natural history of breast cancer is very variable, probably indicating a wide spectrum of different growth rates of the tumour. Therefore it cannot necessarily be assumed that cancers detected by screening at an apparently early stage will behave in the same way as symptomatic cancers at that stage. To prove that screening enables cancer to be cured one needs to compare the number of deaths in a group of women who have been offered screening with those in a comparable group who have not. Unlike the situation in clinical trials of different treatments, comparison of the survival of screen-detected cancers with symptom-detected cancers is inadequate proof, because of selection bias, lead-time bias and length-bias. One randomized controlled trial of screening for breast cancer has so far been published and this shows that women in the group who were offered screening suffered one third fewer deaths from breast cancer than women in the control group, the difference persisting for up to 14 years from the first screening invitation. Further trials are now under way in Canada and various European countries, hoping to confirm this finding and to explore various other issues. Of the screening test methods currently available mammography seems the most sensitive and specific and its radiation hazard is now of almost negligible proportions provided that regular careful monitoring of the equipment is carried out. However it may have the disadvantage of overdiagnosing cases of borderline non-invasive neoplasia which might not progress to invasive cancer within the woman's lifetime. Clinical examination of the breasts is a less satisfactory test in older women but it may be useful in premenopausal women in whom mammography is less sensitive. The validity of self-examination of the breasts by women themselves is still largely unknown, but it is unlikely that compliance with regular breast self-examination will be as high as women's acceptance of screening. Further research is required into the optimal frequency of screening and into its cost-effectiveness.     

Cigarette smoking and the risk of breast cancer

The authors examined the relation between cigarette smoking and breast cancer in the Centers for Disease Control Cancer and Steroid Hormone Study, a multicenter, population-based case-control study. The study compared 4,720 women aged 20-54 years with newly diagnosed breast cancer identified through population-based tumor registries with 4,682 women randomly selected from the same geographic areas. Women who reported ever smoking cigarettes had a risk of breast cancer of 1.2 (95 percent confidence interval 1.1-1.3) compared with never smokers. There was no consistent dose-response pattern with any measure of smoking (pack-years of smoking, average number of cigarettes per day, or total years smoked) and little difference in risk between current and former smokers. There was some variation in risk by age, with slightly higher risk estimates for younger women than for older women. Although current smokers had an earlier natural menopause than did never smokers, the authors found no evidence of a protective effect of cigarette smoking on breast cancer risk. These findings suggest that the risk of breast cancer in women who smoke is the same as, or perhaps slightly higher than, women who have never smoked.     

Lactation in relation to postmenopausal breast cancer.

A modest inverse association between lactation and breast cancer risk has most consistently been observed in premenopausal women, and certain breastfeeding patterns, such as prolonged duration and early age at first lactation, may be important determinants of risk. However, these associations have not generally been observed in relation to postmenopausal breast cancer. As part of a multicenter population-based case-control study, the authors examined postmenopausal breast cancer risk according to breastfeeding characteristics. Breast cancer patients aged 50-79 years were identified from statewide tumor registries in Massachusetts, New Hampshire, and Wisconsin from July 1992 through July 1995. Similarly aged control women were randomly selected from population lists. Information regarding lactation history and breast cancer risk factors was obtained through telephone interviews. This analysis included only data on parous postmenopausal women (3,633 cases and 3,790 controls). After adjustment for age, parity, age at first birth, and other breast cancer risk factors, breastfeeding for at least 2 weeks was associated with a slightly reduced risk of breast cancer in comparison with women who had never lactated (relative risk = 0.87, 95% confidence interval 0.78-0.96). There was only a modest suggestion that increasing cumulative duration of lactation was inversely associated with breast cancer risk; the relative risk for women who had breastfed for > or =24 months was 0.73 (95% confidence interval 0.56-0.94) (p-trend for duration = 0.10). Age at first lactation was not consistently associated with risk. Modest inverse associations appeared to persist even up to 50 years since first lactation. Use of hormones to suppress lactation was not associated with postmenopausal breast cancer, nor was inability to breastfeed related to risk. These results suggest that lactation may have a slight and perhaps long-lasting protective effect on postmenopausal breast cancer risk.     

Case-control evaluation of breast cancer screening efficacy

The feasibility and validity of using case-control methods to evaluate the efficacy of breast cancer screening were investigated using data from the Health Insurance Plan of Greater New York Breast Cancer Screening Trial. Women who died of breast cancer were compared with individually matched controls of the same age who had equal or greater survival times. To minimize the effects of self-selection bias, most analyses focused on the 95 cases and 380 matched controls who had been screened at least once and for whom covariate data were available. A statistically significant effect for being screened more than once versus being screened once, uncorrected for healthy-screenee bias, was found (odds ratio = 0.13, p less than 0.001). After correction for healthy-screenee bias, the effect was not statistically significant (odds ratio = 0.54, p = 0.15). Possible explanations for this statistical nonsignificance are: 1) correction for healthy-screenee bias entails loss of power and 2) the correction procedure used may, under some circumstances, result in bias toward the null hypothesis. Further research into means of eliminating healthy-screenee bias is needed to improve the applicability of case-control methods to the evaluation of screening efficacy.     

Effect of different mammographic radiation exposures on predicted benefits of screening for breast cancer

The benefits and risks of screening for breast cancer, including both mammographic and clinical examinations, are analysed by means of a probabilistic model. The model, applied to previously unpublished data provided by the HIP (Health Insurance Plan of Greater New York) breast cancer screening project, permits more precise stratification by age than previous analyses and allows for incorporation of oncogenic risks due to mammography. It is assumed that, from the tenth year of screening onward, radiation induces 6 cases of breast cancer per year per million women screened per rad delivered to the breast tissue per exam. The predicted pattern of breast cancer cases and deaths is commensurate with that actually observed in the first nine years of the HIP study. In extrapolation to lifetime experience, the model predicts an ultimate decrease in the probability of dying of breast cancer only for women over age fifty at initial screening and an increase in life expectancy for the entire screened group, at an exposure level of three rads per exam. Had radiation dosage been one rad or less per exam, which is within the range now possible with modern equipment and procedures, the radiation risk would not offset even a modest benefit such as is predicted for the younger women, either in number of deaths or years of life expectancy.     

Body size and breast cancer risk assessed in women participating in the Breast Cancer Detection Demonstration Project

In a case-control study that included 2,560 breast cancer cases and 2,679 controls, the authors examined the association between body size and breast cancer with the use of measured height and weight of white US women. The subjects were women aged 26-93 years recruited between 1973 and 1975 for participation in the Breast Cancer Detection Demonstration Project, a nationwide breast cancer screening program. After controlling for the effect of potential confounders, the relative risks of breast cancer across increasing quartiles of height were 1.00, 1.07, 1.15, and 1.27 (p = 0.001, test for trend). The effect of weight independent of height was evaluated using indices of relative weight (e.g., weight/height1.5, weight/height2), and the authors identified excess weight as a risk factor for breast cancer among women who had experienced natural menopause and among women aged 50 years or older at diagnosis. Among women aged 50 years or older, for example, the relative risks of breast cancer for increasing quartiles of weight/height1.5 were 1.00, 1.04, 1.40, and 1.29 (p = 0.0006, test for trend). An inverse association between relative weight and breast cancer risk was suggested for women younger than age 50 years at diagnosis. However, the apparent protective effect of high relative weight was restricted to women with small tumors, suggesting a detection bias.     

The evidence base for breast cancer screening

The history of breast cancer screening is littered with controversy. With 10 trials spanning 4 decades, we have a substantial body of evidence, but with different aims and flaws. Combined analysis of the intention-to-treat results gives an overall relative reduction in breast cancer mortality of 19% (95% CI 12%-26%), which, if adjusted for non-attendance gives an approximate 25% relative reduction for those who attend screening. However, given that 4% of all-cause mortality is due to breast cancer deaths, this translates into a less than 1% reduction in all-cause mortality.An emerging issue in interpretation is the improvements in treatment since these trials recruited women. Modern systemic therapy would have improved survival (models suggest between 12% and 21%) in both screened and non-screened groups, which would result in a lesser difference in absolute risk reduction from screening but probably a similar, or slightly smaller, relative risk reduction. However benefits and harms, particularly over-diagnosis, need to balanced and differ by age-groups. The informed views of recipients of screening are needed to guide current and future policy on screening.     

The Swedish two county trial of mammographic screening for breast cancer: recent results and calculation of benefit.

The Swedish two county trial of breast cancer screening is now in its tenth year. This paper presents detailed results on mortality from breast cancer and from all other causes, and on the population denominators at risk for each of the first 8 years of follow up, for each county separately. These data represent a two year update on the last major report. Results show an increasingly significant deficit in deaths from breast cancer among the 77,092 women invited to screening relative to the 56,000 not invited (RR = 0.68, p = 0.002), with no significant difference between the effects of screening in the two counties (p = 0.5). These results remain the same when adjusted for age. Analysis of all cause deaths shows no significant effect of screening (p = 0.5), nor was there any significant effect of screening on deaths from all causes other than breast cancer (p = 0.9). The rates of deaths from intercurrent illness in breast cancer cases were almost identical in the group invited to screening and the group not invited (p = 0.7). This result remained the same when adjusted for age. We calculate that in the age group 50-69 at entry, one breast cancer death was prevented per 4000 woman/years, per 1460 mammographic examinations, per 13.5 biopsies, and per 7.4 breast cancers detected.     

The validity of different control groups in a case-control study. Oral contraceptive use and breast cancer in young women

The possible selection bias due to the use of different series of controls in case-control studies has been analysed in the Norwegian part of a joint national case-control study in Sweden and Norway of oral contraceptive (OC) use and breast cancer in young women. A total of 105 cases diagnosed 1984-1985 were interviewed in addition to 210 population controls matched for age, 104 neighbourhood controls matched for age and postal address, and 96 hospitals controls matched for age. The relative risk was for each of the sets of controls 1.0 for 8 years and more of total use of OCs (adjusted for age at menarche, parity, age at first full term pregnancy, history of breast cancer in mother, history of benign breast biopsy). An additional questionnaire was sent to those who did not wish to participate (non-attenders). A slight selection bias was found for the population controls with more nulliparous never-users of OCs among the non-attenders than among interviewed controls.     

A case-control study of alcoholic beverage consumption and breast cancer

In many studies, moderate alcohol consumption has been associated with increases in the risk of breast cancer of about 50-100%. The authors examined recent alcoholic beverage consumption in relation to the risk of breast cancer in a case-control study of women aged less than 70 years, conducted in Toronto, Ontario, Canada, from 1982 to 1986: 607 breast cancer cases identified in a cancer hospital were compared with 1,214 controls matched to the cases on neighborhood and decade of age. The subjects were interviewed at home. Confounding factors were controlled by conditional logistic regression. The relative risk estimates for women who consumed alcohol, relative to women who drank less than one alcoholic beverage (drink) per month, were close to 1.0: for women who drank at least one alcoholic beverage per day, the multivariate estimate was 0.9 (95% confidence interval 0.6-1.2). Among subgroups of women, including those at low baseline risk, there was also no association. For a subset of cases compared with hospital controls, once again there was no association. The relative risk (RR) estimate was elevated for women who drank at least one beer daily (RR = 1.7) and reduced for women who drank at least one glass of wine daily (RR = 0.7), but neither estimate was statistically significant. The results suggest that recent alcohol consumption does not influence the risk of breast cancer. Selection bias cannot be ruled out, however. In addition, because determinants of alcohol use are not well understood, control of confounding may have been incomplete in the present study and in other observational studies of alcohol and breast cancer.     

Patterns and Determinants of Breast and Cervical Cancer Non-Screening Among Appalachian Women

Breast and cervical cancer account for nearly one-third of new cancer cases and one-sixth of cancer deaths. Cancer, the second leading cause of all deaths in the United States, will claim the lives of nearly 800,000 women this year, which is particularly unfortunate because effective modes of early detection could significantly reduce mortality from breast and cervical cancer. Researchers examined patterns of non-screening among Appalachian women. In-person interviews were conducted with 222 Appalachian women who fell outside of screening recommendations for timing of Pap tests and mammograms. These women, from six Appalachian counties, were participating in a group-randomized, multi-component trial aimed at increasing adherence to cancer screening recommendations. Results indicated that participants who were rarely or never screened for breast cancer were also likely to be rarely or never screened for cervical cancer. In addition, four key barriers were identified as independently and significantly associated with being rarely or never screened for both cervical and breast cancer. An improved understanding of cancer screening patterns plus the barriers underlying lack of screening may move researchers closer to developing effective interventions that facilitate women's use of screening.     

Alcoholic beverage consumption and breast cancer incidence

Recent case-control studies have suggested that alcohol consumption may be associated with breast cancer incidence. This report is a retrospective cohort study of over 95,000 women who were members of the Kaiser Foundation Health Plan of Northern California. The stated alcohol consumption of these women was recorded at a multiphasic screening examination taken from 1964 to 1972 prior to any diagnosis of breast cancer. The incidence of breast cancer in this cohort was greater for women who drank, and among these drinkers, incidence increased in an irregular trend with heavier alcohol consumption. Control for the effects of race, education, smoking, and reproductive variables related to breast cancer all but eliminated the overall increased relative risk of drinkers compared with that of nondrinkers. However, the relatively small group of women who stated that they had three or more alcoholic drinks per day (5.2 per cent of the total) had a significantly elevated relative risk of 1.4 (p = 0.035) compared with nondrinkers, despite control for all available confounding variables. No significant interaction effect of smoking and alcohol was found. Women who had less than three drinks per day had no increased relative risk over nondrinkers. The results of this study might be explained either by an unrecognized carcinogenic effect of alcohol on breast tissue or by the confounding effect of other factors associated with heavy alcohol use.     

Induced abortion and breast cancer risk

Results from case-control studies suggest that induced abortion may be associated with a small increase in risk of breast cancer. While risk estimates from cohort studies have generally not observed such an association, these studies have had limited information regarding abortion and possible confounding variables. Therefore, we conducted a study among a cohort of post-menopausal women from whom detailed information regarding pregnancy outcomes as well as risk factors for breast cancer had been collected. The study sample included 37,247 Iowa Women's Health Study participants, 55-64 years of age at baseline in 1986, who reported no history of breast, or other, cancer (except non-melanoma skin cancer), and for whom information regarding pregnancy outcomes (that is, live birth, stillbirth, spontaneous abortion, ectopic pregnancy or induced abortion) was available. We used linkage with records of the State Health Registry of Iowa, part of the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program, to estimate the incidence of breast cancer among cohort members through 1995. We calculated age-adjusted relative risks and 95% confidence intervals using Cox proportional hazards regression. Only 653 women (1.8%) reported an induced abortion. The age-adjusted relative risk of breast cancer among women with prior induced abortion compared with those without was 1.1 (95% CI = 0.8-1.6). Relative risks were higher among women whose age at first abortion was less than 20 or at least 30 years, for those whose abortion took place after their first birth or who never gave birth, and for those with early termination (0-2 months). These estimates varied from 1.3-1.7, but the confidence intervals around each were wide. Since most women in this cohort were beyond their reproductive years when abortion became legal in 1973, the low prevalence of induced abortion argues for a cautious interpretation.     

Breast cancer and oral contraceptives: patterns of risk among parous and nulliparous women--further analysis of the Swedish-Norwegian material

A Swedish-Norwegian case-control study comprising 473 women less than 45 years old with newly diagnosed invasive breast cancer diagnosed in 1984-85, and 722 age-matched control women, was reanalyzed to evaluate if nulliparous women who had used oral contraceptives (OCs) were at particular risk for breast cancer. The relative risk for nulliparous women who had used OCs for eight years or more was 4.3 (95% confidence interval, 1.4-13.1), and parous women with the same duration of use had relative risk 1.7 (0.7-4.2) as compared to nulliparous and parous women, respectively, who had never used OCs. Parous women who had used OCs for twelve years or more after their first full-term pregnancy had a relative risk of 3.0 (1.3-7.4). The findings from the study suggest that nulliparous women may be particularly susceptible to the risk for breast cancer with long-term OC use.     

Risk factors for breast cancer by mode of diagnosis: some results from a breast cancer screening study.

We have investigated factors affecting the probability that a woman with breast cancer participating in a mammographic screening programme will be diagnosed by the screen. Data from a large American case-control study, with subjects drawn from women participating in an annual screening programme, were used. During the screening programme, 409 cases were identified, the mode of diagnosis being screen detection for 331 and interval detection for 78. No significant relationships were found between mode of diagnosis and age, age at menarche, oral contraceptive use, age at first live birth, age at menopause or history of maternal breast cancer. There was a non-significant trend for particular mammographic patterns to be associated with interval detection. However relative risk of breast cancer and probability of interval detection were observed to increase about the time of the menopause. These results suggest that the 3 yearly mammography programme being introduced in the UK might be improved if an extra examination was included around the time of the menopause.     

Breast cancer screening among relatives of women with breast cancer.

BACKGROUND. National surveys indicate that only 15% to 30% of all women in the general population 50 years of age or older have an annual mammogram. METHODS. We studied first-degree female relatives of women with breast cancer, who are at elevated risk of disease, to describe the breast cancer screening practices of these relatives and to improve their practices through a program of intensive education. We report here the screening behaviors of 2471 relatives of women with breast cancer. RESULTS. Self-reported behaviors were as follows: 49% performed monthly breast self-examination and 70% had annual breast examinations by a medical professional. Of 983 women 50 years of age or older, 49% had had a mammogram, but only 14% have a mammogram annually. Of women 50 years of age or older who had never had a mammogram, 92% reported never having had one recommended by a medical professional. CONCLUSIONS. Our findings indicate that screening behaviors in relatives of breast cancer patients are not substantially different from those of women in the general population. Enhanced efforts both to educate medical professionals and to encourage women to demand screening mammography are necessary to reduce breast cancer mortality.     

Oral contraceptive use and premenopausal breast cancer in Sweden and Norway: possible effects of different pattern of use

Different use of oral contraceptives (OCs) in relation to reproductive histories and age might explain the conflicting results found in studies from different countries of OC use and premenopausal breast cancer. A population-based case-control study in Sweden and Norway has been analysed separately for the two countries. The study consists of 317 Swedish and 105 Norwegian cases diagnosed 1984-1985 with 317 Swedish and 210 Norwegian controls. The results for each country separately are consistent with the joint analysis showing increased risk for breast cancer with increased duration of OC use with the exception of that for women with more than 15 years since first use. The relative risk of breast cancer for more than four years of use among Norwegian women was 0.6 (95% confidence internal (Cl), 0.2-1.8). In both countries there was a non-significant higher risk associated with increasing duration of use before first full-term pregnancy. Analyses for surveillance bias show no evidence of bias as explanation for the association between total duration of OC use and breast cancer.     

Evaluating the survival of cancer cases detected by screening

Early detection of cancer by screening advances the date of diagnosis, but may or may not affect survival. To assess the survival benefit associated with early detection, one must estimate the distribution of time survived post lead-time, that is, after the unknown date when clinical diagnosis would have occurred in the absence of screening. One can then compare the adjusted survival of screen-detected cancer cases to other groups of cases not diagnosed by screening. This paper describes a model for the survival of screen-detected cases, with a hazard function that depends on an individual's lead time, the duration of preclinical disease, and the time since diagnosis. The model is fitted to the ten year survival data from the 132 screen-detected cases of breast cancer in the well-known HIP (Health Insurance Plan of Greater New York) study. Comparison with the survival of several groups of cancer cases not detected by screening (interval cases arising clinically in persons previously screened, cases among persons who refuse screening, and cases among randomized controls not offered screening) yields various estimates of benefit. Use of the interval cases for comparison gives an estimate of about 21 breast cancer deaths prevented among 20,166 women screened in the HIP study; use of the data from the randomized controls gives an estimate of about 25 prevented deaths. The former estimate derives from the screened group of women only, and so the same method of evaluation may also be applied to community screening programmes and other situations that do not entail randomization.