Screening women aged less than 50 years with a family history of breast cancer

Family history is an important breast cancer risk factor and is a common reason for referral to specialist breast clinics for consideration of breast screening. The aims of this study were to determine cancer detection rates and prognostic features of breast cancers identified in women aged less than 50 years at increased risk of breast cancer who attend a Family History Breast Screening Clinic (FHC). Between January 1988 and December 1995, 1371 asymptomatic women aged less than 50 years underwent annual clinical breast examination and biennial mammography due to a family history of breast cancer. A total of 29 cancers (23 invasive and 6 in situ) were detected or presented as interval cancer during a mean follow-up of 22 months (range 0-96 months). This gave a relative risk for invasive breast cancer in this high-risk group of 5 when compared with an age-matched female population in the U.K. The cancer screening detection rates were similar to those of women aged 50 years or over undergoing population screening in the NHS Breast Screening Programme (NHSBSP)--FHC prevalent screen 8 per 1000 screening visits versus NHSBSP 6.5 per 1000, FHC incident screen 3.3 per 1000 screening visits versus NHSBSP 3.8 per 1000. A higher proportion of in situ cancers were detected in the FHC screened group compared with cancers identified in symptomatic patients from an age-matched risk group (21% versus 4%). No differences were demonstrated for invasive tumour size, grade or lymph node stage between symptomatic and screened women. The early results of this study suggests that young women at risk of breast cancer due to a family history may benefit from regular breast screening due to the early detection of in situ lesions.     

The Gothenburg Breast Cancer Screening Trial: preliminary results on breast cancer mortality for women aged 39-49

We carried out a randomized trial of invitation to screening mammography in the city of Gothenburg, Sweden, to estimate the effect of screening on breast cancer mortality in women under age 50 years. A total of 11,724 women aged 39-49 were randomized to the study group, which was invited to mammographic screening every 18 months; 14,217 women in the same age range were randomized to a control group, which was not invited to screening until the fifth screen of the study group. Breast cancers diagnosed in both groups between randomization and immediately after the first screen of the control group were followed up for death from breast cancer to the end of December 1994. There was a significant 44% reduction in mortality from breast cancer in the study group compared to the control group (relative risk [RR] = 0.56, P = 0.042, 95% confidence interval [CI]: 0.32-0.98). A conservative estimate based on removal of the cancers detected at the first screen of the control group gave an RR = 0.59 (P = 0.069, 95% CI: 0.33-1.05). The true answer is likely to lie between the two estimates. These data suggest that mammographic screening can reduce breast cancer mortality in women under age 50, particularly if high-quality mammography is used and a short interscreening interval is adhered to.     

Knee position error detection in closed and open kinetic chain tasks during concurrent cognitive distraction

OBJECTIVES: To estimate the number of breast cancer deaths induced by low dose radiation in breast cancer screening programmes compared with numbers prevented. METHODS: A computer simulation model on the natural history of breast cancer was combined with a model from BEIR-V on induced breast cancer mortality from low levels of radiation. The improvement in prognosis resulting from screening was based on the results of the Swedish overview of the randomised screening trials for breast cancer and the performance of screening in the Netherlands. Different scenarios (ages and intervals) were used to explore the objectives. Sensitivity analyses were carried out for latency period, dose of mammography, sensitivity of the screening test, early detection by screening of induced breast tumours, and new 1996 risk estimates by Howe and McLaughlin. RESULTS: For a screening programme, age group 50-69, two year interval, 2 mGy per view, the balance between the number of deaths induced versus those prevented was favourable: 1:242. When screening is expanded to the age group 40-49 with a one or two year interval the results may be less favourable, that is, 1:66 and 1:97. According to these scenarios and with the Dutch scenario as reference, one breast cancer death from radiation may be expected to occur to save eight extra deaths from breast cancer. If screening was equally effective in young women as in women aged 50-69, the marginal value was 1:+/- 30. Assuming detection of induced cancers by screening could influence the ratios by about 30%, but did not substantially change the conclusions. The new risk estimates by Howe and McLaughlin resulted in five times to eight times favourable ratios breast cancer deaths induced to prevented. Besides age group of screening, dose of mammography is the other determinant of risk. CONCLUSIONS: For screening under the age of 50, the balance between the number of breast cancer deaths prevented by screening compared with the number induced by radiation seem less favourable. Credibility intervals were however wide, because of many uncertainties of radiation risk at very low doses.     

Quality assurance and cancer detection rates in a provincial screening mammography program. Work in progress

In 1990, a provincial screening program was inaugurated in Alberta, a Canadian province of 2.4 million people. The goal of the program is to decrease the number of deaths from breast cancer by 30% in women aged 50-69 years. In the first 18 months of program operations, efforts were concentrated on high levels of quality assurance in all areas of program activities. In particular, the abnormality referral rates, cancer detection rates, and size and stage of mammographically detected cancers were evaluated. Of the 9,553 women seen, 8,524 were between the ages of 50 and 69 years. Reported abnormality rates were initially more than 16%, but were brought down steadily to less than 5%. Cancer detection rates increased with age, ranging from 1.9 cancers detected per 1,000 women aged 40-49 years to 14.1 cancers per 1,000 women aged 70 years and older. Forty-one of the 61 cancers detected (67%) were less than 1.5 cm in diameter. Forty-three of the 52 cancers (83%) in which the nodal status was known were node negative. At the conclusion of the first 18 months of operation, interpretation parameters were within the target zones expected for a population-based screening program.     

Relation between the incidence of invasive cervical cancer and the screening interval: is a five year interval too long?

OBJECTIVE: To examine the incidence of invasive cervical cancer per 100,000 women years at risk and relative risk according to screening history among eligible women aged 25-69 in Southampton and South West Hampshire during the three years after completion of the first round of comprehensive screening. RESULTS: There was a significantly higher incidence of invasive cervical cancer in women who had not been screened during the preceding 0.5-5.5 years than in those who had been screened (relative risk (RR) 2.6; 95% confidence interval (CI) 1.6 to 4.3). Among the latter group of women (with interval cancers) there was a significantly higher incidence in those with a long interval of 3.5-5.5 years since their most recent smear than in those with a short interval of 0.5-3.5 years (RR 2.2; 95% CI 1.3 to 3.8). Among women with non-interval cancers, there was a significantly higher incidence among those who had no cytology record than among those who had been screened but were overdue for a smear (RR 3.0; 95% CI 1.2 to 7.3). When screen detected cancers were excluded from the figures the relative risks for all the comparative groups described above were greater, though the 95% confidence limits were wider because the numbers were smaller. The most pronounced difference in incidence was between symptomatic cancers in women with a short screening interval (5.8 per 100,000 women years at risk) and in women with no cytology record (71.3 per 100,000 years at risk). Most cancers were interval cancers (76%) because of the high screening coverage: 89.2% of eligible women aged 25-69 had been screened during the preceding 0.5-5.5 years. The overall incidence per 100000 women years at risk approached that of interval cancers, and was nearer to that observed in the short than the long interval because 74.7% of women had been screened within 3.5 years. CONCLUSION: The results confirm the effectiveness of screening but suggest that a five year screening interval may be too long, at least during the early rounds of screening.     

Updated overview of the Swedish Randomized Trials on Breast Cancer Screening with Mammography: age group 40-49 at randomization

The purpose of this overview is to estimate more precisely the long-term effect of mammography screening by adding four more years of follow-up to women aged 40-49 years in the four Swedish trials on mammography screening. Data from the four, trials were merged and linked to the Swedish Cancer and Cause of Death Register for 1958-1993 and 1951-1993 respectively to identify date of breast cancer diagnosis and cause and date of death. The invited and control groups comprised 48,569 and 40,247 women respectively. At the December 1993 follow-up, 602 and 482 breast cancer cases were identified in the two groups respectively, of which 104 and 111 had breast cancer as the underlying cause of death. This corresponds to a relative risk (RR) of 0.77 (95% CI: 0.59-1.01) for the two groups. In the 40-44 age group at randomization, 94% of breast cancer patients in the study and 89% in the control group were diagnosed before the age of 50; however, among breast cancer deaths in this age group, only two in the invited and five in the control group died after age 50. At follow-up of women 40-44 years at randomization 208 women in the invited and 184 in the control group were reported to the Cancer registry with breast cancer. Out of these 195 (94%) and 163 (89%) respectively were reported before the age of 50. Further, the relative risk for the age group 40-44 years at randomization by age at follow-up was 1.11, 0.51 and 0.46 for the age groups 45-49, 50-54, and 55-59 at follow-up. This study shows a 23% reduction in the breast cancer mortality in women 40-49 years at randomization achieved from a median trial time of 7.0 years, a median follow-up time of 12.8 years, and a screening interval of 18-24 months. Almost all of the effect in the 40-44 year age group at randomization was due to screening before the age of 50.     

CD1d-mediated recognition of an alpha-galactosylceramide by natural killer T cells is highly conserved through mammalian evolution

BACKGROUND: Although increasing rates of breast carcinoma incidence have been observed in Asian countries, appropriate strategies for detecting early stage breast carcinoma in such communities have been difficult to formulate, particularly because no large population screening trial specifically involving Asian women has been reported. The objective of this study was to evaluate the effectiveness and quality of mammography as a screening technique for Singaporean women, who are predominantly Chinese. METHODS: In this prospective study, 166,600 women in Singapore ages 50-64 years were randomized to either 2-view mammography without physical examination (67,656) or observation (97,294, controls) over 2 years. RESULTS: Of these women, 28,231 (41.7%) responded and were screened; they were more likely to be married, have more formal education, be working, be Chinese, and be in a higher socioeconomic group (P < 0.001 for all variables). To assess for response bias that could affect outcome, results were also evaluated for nonrespondents (n = 39,425). The incidence rate of cancers among nonrespondents (1 per 1000 woman-years) was less than the 1.3 in women not invited to have screening (P = 0.03, relative risk [RR], 1.3; 95% confidence interval [CI], 1.0-1.7). However, cancers arising from nonrespondents did not differ significantly in stage distribution when compared with cancers within the control group. For every 1000 women screened, 4.8 cancers were detected. The prevalence ratio (the number of cancers detected per 1000 women at first screening divided by the corresponding incidence rate in controls per year) was 3.6 for screened women and 2.4 for women invited to have screening. The majority of cancers detected through screening were early stage, with 64% as either ductal carcinoma in situ (26%) or Stage I disease (38%) and was significantly more than the corresponding 26% in women not invited to have screening (P < 0.001). When only invasive cancers were considered, screened women still had more early cancers, with 65% having no lymph node involvement, compared with 47% in the group not invited to have screening (P = 0.001; RR, 1.4; 95% CI, 1.2-1.7). Women who were screened had half the risk of having Stage II or later cancers (P < 0.0001; RR, 0.5; 95% CI, 0.4-0.7) when compared with women not invited to have screening. This higher detection rate of early cancers through screening was accomplished with acceptable recall rates of 8% for further mammographic films or physical examination and a biopsy rate of 1.0% (10 per 1000 women screened). The interval cancer rate was 2.1 per 10,000 women screened in the first year of follow-up. CONCLUSIONS: These positive results of intermediate measures suggest that, in Asian communities, screening mammography could be an important modality for detecting early stage breast carcinoma. However, the low compliance rates suggest that health education efforts must focus on issues related to acceptability if such programs are to succeed.     

Campaign for cervical cancer screening with vaginal smears in women aged 50-69 years in Isère (France). Results of the first round (January 1991-June 1993)

The department of Isère, which is involved since 1990 in a breast cancer screening campaign concerning women aged 50 to 69, has managed to associate a cervical and colorectal cancers screening program. The target sample size is 98,000 individuals. Women are asked to refer their general practitioner or gynaecologist for cervicovaginal smears. Each woman is invited at a screening interval of 30 months. The results of the first invitation (November 1990-December 1992) are reported. Thus 29,570 women did referred, so that the screening uptake is 30% and 20,083 women (68%) had Pap smears inside the screening program. 1.1% of the smears were unsatisfactory and 1.2% of the tests showed abnormalities. Ninety-six percent of the women who had been referred for further examinations have been followed up. Thirty-eight women (representing 17% of smears with abnormalities) had surgery (conisation, hysterectomy, Wertheim). Among them, 5 cases of invasive cervical carcinoma and 25 in situ carcinoma were detected. The detected cancer prevalence per 1,000 women screened is 1.5/1000. An organised screening program for cervical cancer in association with breast cancer screening, seems to be an effective way of increasing smears realisation in women aged 50 to 69, and of involving general practitioners in cervical cancer screening.     

Progressive osseous heteroplasia: a case report

STUDY OBJECTIVE: To assess the impact of a breast clinic on a specific target population and evaluate early diagnosis performance indicators for breast cancer in the presence of a self referral policy. DESIGN: Women living in Florence between 1980 and 1989 who had undergone mammography at a self referral breast clinic were studied. Main outcome measures were the use of mammography in relation to age, symptoms, and the interval between two subsequent tests, and early diagnosis performance indicators were the detection rate (DR), the prevalence/incidence ratio, and the proportion of early detected cancers. Performance indicators were compared with those from formal screening programmes. SETTING: Florence, Italy. PATIENTS: All mammograms performed at the clinic from 1980-89 in 40-69 year old women living in Florence were examined (n = 42,226). Records included the date of birth and of the examination, the reason for testing (asymptomatic/presence of pain/presence of symptoms other than pain), and the TNM classification for breast cancer cases. MAIN RESULTS: The total number of mammograms performed per annum increased by 70% over the decade, but much of this was routine repeat mammography (54.1% in 1989). Rates of first examinations in asymptomatic women increased in the second half of the decade from 17 per 1000 in 1985 to 31 per 1000 in 1989. Mammographic coverage decreased with increasing age from 12.6% in 40-49 year olds to 6.0% in 60-69 years old. Performance indicators of the activity in asymptomatic women were comparable with those expected in service screening. The proportion of not advanced cancers detected in asymptomatic women was 62.3% with a DR of 5.3 per 1000, and the average prevalence/incidence ratio was 2.9. CONCLUSIONS: High quality mammography performed in a breast clinic in self referred asymptomatic women can achieve as good results as a formal invitation screening service. Only a few of these women will benefit, but those who do are likely to be younger (40-49 year old women).     

Glycation accelerates the oxidation of low density lipoprotein by copper ions

The American Cancer Society recommends periodic mammography, clinical breast examination and breast self-examination beginning at age 40 years for asymptomatic women at average risk of breast cancer. Although there is substantial evidence from meta-analyses and non-randomized studies to support these recommendations, individual randomized clinical trials of breast cancer screening have not demonstrated mortality reduction in women aged 40-49 years. The opportunity to study this issue further in the United States has been diminished by the high prevalence of screening already being conducted in that population of younger women. The International Union Against Cancer, the American Cancer Society and the National Cancer Institute of the United States have convened a series of workshops and planning meetings to consider the available data and outline plans for future research. Plans are being developed to conduct a randomized trial of mammography in women younger than 50 years in multiple European sites. Successful completion of this trial may provide critical data on efficacy of breast cancer screening in younger women.     

Radiation risk from screening mammography of women aged 40-49 years

Although direct evidence of carcinogenic risk from mammography is lacking, there is a hypothetical risk from screening because excess breast cancers have been demonstrated in women receiving doses of 0.25-20 Gy. These high-level exposures to the breast occurred from the 1930s to the 1950s due to atomic bomb radiation, multiple chest fluoroscopies, and radiation therapy treatments for benign disease. Using a risk estimate provided by the Biological Effects of Ionizing Radiation (BEIR) V Report of the National Academy of Sciences and a mean breast glandular dose of 4 mGy from a two-view per breast bilateral mammogram, one can estimate that annual mammography of 100,000 women for 10 consecutive years beginning at age 40 will result in at most eight breast cancer deaths during their lifetime. On the other hand, researchers have shown a 24% mortality reduction from biennial screening of women in this age group; this will result in a benefit-to-risk ratio of 48.5 lives saved per life lost and 121.3 years of life saved per year of life lost. An assumed mortality reduction of 36% from annual screening would result in 36.5 lives saved per life lost and 91.3 years of life saved per year of life lost. Thus, the theoretical radiation risk from screening mammography is extremely small compared with the established benefit from this life-saving procedure and should not unduly distract women under age 50 who are considering screening.     

Effects of various phosphodiesterase-inhibitors, forskolin, and sodium nitroprusside on porcine detrusor smooth muscle tonic responses to muscarinergic stimulation and cyclic nucleotide levels in vitro

The Gail model is being used increasingly to determine individual breast cancer risk and to tailor preventive health recommendations accordingly. Although widely known to the medical and biostatistical communities, the risk factors included in the model may not be salient to the women to whom the model is being applied. This study explored the relationship of the individual Gail model risk factors to perceived risk of breast cancer and prior breast cancer screening among women with a family history of breast cancer. Data from baseline interviews with 969 women found a striking disparity between the objective risk factors included in the model and the accuracy of perceived risk and screening behaviors of this population, particularly among women over the age of 50 years. Risk perception accuracy was unrelated to all of the Gail model risk factors for all age groups. Reported mammography adherence was only associated with having had a breast biopsy in both age groups. Breast self examination (BSE) practice was independent of all measured factors for both age groups. These findings support the need for further research to identify additional determinants of risk perception and motivators of screening behavior.     

Efficacy of screening mammography among women aged 40 to 49 years and 50 to 69 years: comparison of relative and absolute benefit

In randomized controlled trials, screening mammography has been shown to reduce mortality from breast cancer about 25% to 30% among women aged 50 to 69 years after only five to six years from the initiation of screening. Among women aged 40 to 49 years, trials have reported no reduction in breast cancer mortality after seven to nine years from the initiation of screening; after 10 to 14 years there is a 16% reduction in breast cancer mortality. Given that the incidence of breast cancer for women aged 40 to 49 years is lower and the potential benefit from mammography screening smaller and delayed, the absolute number of deaths prevented by screening women aged 40 to 49 years is much less than in screening women aged 50 to 69 years. Because the absolute benefit of screening women aged 40 to 49 years is small and there is concern that the harms are substantial, the focus should be to help these women make informed decisions about screening mammography by educating them of their true risk of breast cancer and the potential benefits and risks of screening.     

Role and evaluation of mammography and other imaging methods for breast cancer detection, diagnosis, and staging

Mammographic screening of women age 40 and older can reduce breast cancer deaths by at least 30% to 40%. However, not all cancers are detected by mammography. Although a new supplementary modality for screening could, in theory, fill in this detection gap, such utilization must be based on rigorous demonstration of its ability to consistently and frequently find early cancers missed by mammography, such as those occurring in dense breasts or rapidly growing interval cancers that surface clinically between mammographic screens. After an abnormality is found at mammographic screening, supplementary mammographic views and/or ultrasound are now used to match the finding with an ACR BIRADS final diagnostic assessment category to indicate the relative likelihood of a normal, benign, or malignant diagnosis so that routine screening, short interval follow-up, or biopsy can then be advised. Appropriate categorization will maximize early cancer detection and minimize false-positive biopsies. Application of a new imaging method to this type of diagnostic evaluation requires well-designed studies to determine its effectiveness for this purpose.     

The health status of adult survivors of cancer in childhood

Based on an extensive cost-effectiveness analysis, the Dutch nation-wide breast cancer screening programme started in 1990, providing a biennial screen examination to women aged 50 to 69 years. The programme is monitored by the National Evaluation Team, which annually collects tabulated regional evaluation data to determine performance indicators. This study presents (trends in) the outcomes of initial and subsequent screening rounds, 1990-1995, and compares them to the predictions of the cost-effectiveness-analysis. Up to 1996, 88% of the target population was covered by the programme and more than 2.4 x 10(6) women were invited. The overall attendance rate was 77.5% with little differences between screening rounds and age groups; the highest rate was found in non-urbanised areas (82.4%). Of 1,000 initially (and 2 years thereafter) screened women, 13.4 (6.6) were referred for further investigation, 9.7 (4.4) were biopsied and 6.4 (3.4) had breast cancer. The positive predictive values of screen test and biopsy were 47% (51%) and 66% (78%), respectively. DCIS was diagnosed in 0.9 (0.5) and invasive cancers < or = 10 mm in 1.5 (1.0) per 1,000 screens. Lymph node metastases were found in 28% (24%) of the invasive cancers. Except the increasing attendance, which was much higher than expected, the results were fairly constant over the years. Contrary to initial screens, the results of subsequent screens did not fulfil expectations with regard to breast cancer detection and tumour size distribution. We conclude that the nation-wide screening programme is being implemented successfully. Given the results, the programme should contribute to a substantial breast cancer mortality reduction in the future. The discrepancy between observed and expected results in subsequent screens has to be watched carefully.     

Cutaneous gangrene secondary to metastatic calcification in end stage renal failure--a case report

The belief that oestrogens are involved in the pathogenesis both of testicular cancer in young men and of cancers of the endometrium and female breast has become widespread. In a search for possible hormonal links between these cancers, we investigated the cancer pattern in a cohort of women who had given birth to sons who developed testicular cancer. Particular focus, was given to oestrogen-related cancers. The present retrospective population-based cohort study is based on data from the Danish Cancer Registry. Mothers of 2,204 testicular-cancer patients were followed for the occurrence of cancer over a total of 70,063 person years. The ratio of observed cancers in the cohort over the expected numbers based on cancer incidence in the underlying female population served as measure of the relative risk (RR). The RR of developing breast cancer among mothers of testicular-cancer patients was 0.8 (95% confidence interval 0.6-1.1), the relative risk of endometrial cancer 0.6 (0.3-1.0) and of ovarian cancer 1.0 (0.6-1.6). Mothers of testicular-cancer patients are not at increased risk of developing oestrogen-related cancers.     

Long-term survival of experimental calves with a left ventricular assist impeller pump

Screening with mammography in order to detect early curable breast cancer has been widely used during the last 2-3 decades. Especially an overview of 4 randomised trials in Sweden has shown a convincing short-term relative reduction of the breast cancer mortality while the long-term absolute effect on this mortality has been impossible to study due to screening of the control groups after some years. There is, however, rather general consensus about the value of screening in women above 50 years of age whereas screening in the age group 40-49 is still controversial due to the low rate of mammographically demonstrable cancers and the high rate of recalls for supplementary mammography, clinical examinations and biopsies in relation to cancers found. Recent follow-up of the pooled Swedish randomised trials have shown an about 20% almost significant reduction of the breast cancer mortality in women aged 40-49 at randomisation but the design of these trials does not allow an adequate estimation of the extra benefit obtained by starting periodical screening at age 40 instead of at age 50. The author proposes that screening in the age group 40-49 should be regarded as experimental and subject to proper randomised trials of a type on-going in UK and planned within UICC.     

Efficacy of bilateral prophylactic mastectomy in women with a family history of breast cancer

BACKGROUND: Options for women at high risk for breast cancer include surveillance, chemoprevention, and prophylactic mastectomy. The data on the outcomes for surveillance and prophylactic mastectomy are incomplete. METHODS: We conducted a retrospective study of all women with a family history of breast cancer who underwent bilateral prophylactic mastectomy at the Mayo Clinic between 1960 and 1993. The women were divided into two groups - high risk and moderate risk - on the basis of family history. A control study of the sisters of the high-risk probands and the Gail model were used to predict the number of breast cancers expected in these two groups in the absence of prophylactic mastectomy. RESULTS: We identified 639 women with a family history of breast cancer who had undergone bilateral prophylactic mastectomy: 214 at high risk and 425 at moderate risk. The median length of follow-up was 14 years. The median age at prophylactic mastectomy was 42 years. According to the Gall model, 37.4 breast cancers were expected in the moderate-risk group; 4 breast cancers occurred (reduction in risk, 89.5 percent; P<0.001). We compared the numbers of breast cancers among the 214 high-risk probands with the numbers among their 403 sisters who had not undergone prophylactic mastectomy. Of these sisters, 38.7 percent (156) had been given a diagnosis of breast cancer (115 cases were diagnosed before the respective proband's prophylactic mastectomy, 38 were diagnosed afterward, and the time of the diagnosis was unknown in 3 cases). By contrast, breast cancer was diagnosed in 1.4 percent (3 of 214) of the probands. Thus, prophylactic mastectomy was associated with a reduction in the incidence of breast cancer of at least 90 percent. CONCLUSIONS: In women with a high risk of breast cancer on the basis of family history, prophylactic mastectomy can significantly reduce the incidence of breast cancer.     

Population attributable fraction estimation for established breast cancer risk factors: considering the issues of high prevalence and unmodifiability

Established breast cancer risk factors, in addition to being relatively unmodifiable, are highly prevalent among US women. Previous reports of population attributable fraction for the established risk factors have used definitions that resulted in 75-100% of women in the source population labeled exposed. The practical value of such estimates has not been discussed; further, the estimates have frequently been misinterpreted. In the context of examining the interpretation and public health value of such estimates, the authors demonstrate the sensitivity of the population attributable fraction to changes in exposure cutpoints. They use data from the Carolina Breast Cancer Study, a case-control study of breast cancer conducted in North Carolina between 1993 and 1996. For the four established risk factors (menarche before age 14 years, first birth at age 20 years or later/nulliparity, family history of breast cancer, and history of benign breast biopsy), the estimated population attributable fraction was 0.25 (95% confidence interval 0.06-0.48). Over 98% of the source population was exposed to at least one of these risk factors. The population attributable fraction estimate was reduced to 0.15 when more restrictive definitions of early menarche (less than age 12 years) and late age at first full-term pregnancy (30 years or more) were used (proportion exposed, 0.62). Population attributable fractions for established breast cancer risk factors probably have little public health value because of both the high proportions exposed and the relative unmodifiability of the risk factor distributions.     

Recent results from the Swedish Two-County Trial: the effects of age, histologic type, and mode of detection on the efficacy of breast cancer screening

The effect of mammographic screening in reducing mortality from breast cancer is known to be smaller and more delayed in women aged 40-49 than in women over 50. In this study, we investigated how these phenomena relate to histology-specific breast cancer incidence and mortality. The data are from 2,468 women with breast cancer who participated in the Swedish Two-County Trial. The overall relative breast cancer mortality of invited to noninvited women aged 40-49 was 0.87, and the relative mortality from poorly differentiated (grade 3) ductal carcinoma was 0.95. These results were not statistically significant. The corresponding relative risks for invited women aged 50-74 were a statistically significant 0.65 and 0.61. We conclude that in this trial, with a two-year interscreening interval, the smaller and later effect of invitation to screening on breast cancer mortality in women 40-49 years old is due to the failure of screening to reduce mortality from grade 3 ductal carcinoma in this age group.