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.     

The quality and interpretation of mammographic screening trials for women ages 40-49

Using MEDLINE and the bibliographies of retrieved articles and reviews, we identified and systematically reviewed the quality and results of all randomized trials of mammographic screening that included women less than 50 years of age. Eight randomized trials were identified, 7 of which included women less than 50. Identified trials were assessed for the following design features: (a) method of randomization, (b) documented comparability of baseline data, (c) standardized criteria for breast cancer death, (d) blinded review of cause of death, (e) completeness of follow-up, and (f) use of an "intention to treat analysis." The quality of trials was generally high, with a total of almost 160,000 women randomized. In women aged 40-49 at entry, the overall, absolute risk difference between those invited and those not was 0.0004 (95% CI: 0 to 0.0009). Yet, what does this mean to a 40-year-old women considering screening? If 10,000 women aged 40-49 years were screened regularly, then after a decade there would be about 4 less breast cancer deaths? Is that worthwhile? This is a difficult question, and it needs to be weighed against the problems arising from false positives and ductal carcinoma in situ. We recommend that women in this age group intending to be screened should be fully informed of these results in terms of absolute benefit.     

Benefit of screening mammography in women aged 40-49: a new meta-analysis of randomized controlled trials

Eight randomized controlled trials (RCTs) of screening mammography have been conducted involving women aged 40-49 at entry. Current data are now available from these trials at 10.5 to 18 years of follow-up (average follow-up time: 12.7 years). Meta-analysis has been performed using a Mantel-Haenszel estimator method to combine current follow-up data from the eight RCTs of mammography that included women aged 40-49 at entry, including new follow-up data presented at the NIH Consensus Development Conference held January 21-23, 1997. Combining the most recent follow-up data on women aged 40-49 at entry into all eight RCTs yields a statistically significant 18% mortality reduction among women invited to screening mammography (relative risk: 0.82; 95% confidence interval: 0.71-0.95). Combining all current follow-up data on women aged 40-49 at entry into the five Swedish RCTs yields a statistically significantly 29% mortality reduction among women invited to screening (relative risk: 0.71; 95% confidence interval: 0.57-0.89). Meta-analysis including the most recent follow-up data from all eight RCTs involving women aged 40-49 at entry demonstrates for the first time a statistically significant mortality reduction due to regular screening mammography in women of this age group.     

Cost-effectiveness of extending screening mammography guidelines to include women 40 to 49 years of age

BACKGROUND: Screening mammography is recommended for women 50 to 69 years of age because of its proven efficacy and reasonable cost-effectiveness. Extending screening recommendations to include women 40 to 49 years of age remains controversial. OBJECTIVE: To compare the cost-effectiveness of screening mammography in women of different age groups. DESIGN: Cost-effectiveness analysis done using Markov and Monte Carlo models. PATIENTS: General population of women 40 years of age and older. INTERVENTIONS: Biennial screening from 50 to 69 years of age was compared with no screening. Screening done every 18 months from ages 40 to 49 years, followed by biennial screening from ages 50 to 69 years, was compared with biennial screening from ages 50 to 69 years. MEASUREMENTS: Life-expectancy, costs, and incremental cost-effectiveness. RESULTS: Screening women from 50 to 69 years of age improved life expectancy by 12 days at a cost of $704 per woman, resulting in a cost-effectiveness ratio of $21,400 per year of life saved. Extending screening to include women 40 to 49 years of age improved life expectancy by 2.5 days at a cost of $676 per woman. The incremental cost-effectiveness of screening women 40 to 49 years of age was $105,000 per year of life saved. On the basis of a multiway sensitivity analysis, there is a 75% chance that screening mammography in women 50 to 69 years of age costs less than $50,000 per year of life saved, compared with a 7% chance in women 40 to 49 years of age. CONCLUSION: The cost-effectiveness of screening mammography in women 40 to 49 years of age is almost five times that in older women. When breast cancer screening policies are being set, the incremental cost-effectiveness of extending mammographic screening to younger women should be considered.     

Breast cancer in women who undergo screening mammography: relationship of hormone replacement therapy to stage and detection method

PURPOSE: To compare the breast cancer stages and detection methods in screened women who receive hormone replacement therapy (HRT) with those in screened women who do not receive HRT to determine whether HRT affects the stage or mammographic detection of malignancy. MATERIALS AND METHODS: One hundred fifteen cases of breast cancer in women (age range, 55-65 years) in whom at least one screening mammogram had been obtained at least 24 months before diagnosis and in whom the history regarding HRT could be determined were reviewed retrospectively. Statistical analysis was performed with CHI-2 analysis and the Fischer exact test. RESULTS: The cancer stages in the 58 women who received HRT were stage 0 in 15 (26%), stage I in 28 (48%), stage II in 13 (22%), and stage III in two (3%) women. The stages in the 57 women who did not receive HRT were stage 0 in 19 (33%), stage I in 24 (42%), stage II in 11 (19%), stage III in two (4%), and stage IV in one (2%) woman. Cancers in 38 (67%) of the women who did not receive HRT and in 38 (66%) of those who did receive HRT were detected with mammography alone; false-negative mammograms were obtained in five (9%) women in the non-HRT group and in four (7%) women in the HRT group (P = .89). CONCLUSION: Among screened women who developed breast cancer, there were no significant differences in cancer stages or in the number of mammographically detected cancers or false-negative mammograms between the HRT group and the non-HRT group.     

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.     

The breast cancer screening controversy and the National Institutes of Health Consensus Development Conference on Breast Cancer Screening for Women Ages 40-49

PURPOSE: Unaccustomed exercise is associated with an elevated plasma creatine kinase (CK), myofibrillar inflammation, and delayed onset muscle soreness (DOMS). Nonsteroidal antiinflammatory drugs (NSAID) may attenuate DOMS and indirect indices of inflammation in humans. METHODS: We studied the effects of an NSAID (naproxen sodium (500 mg, 2 times a day for 48 h)) taken before and after resistance exercise in eight healthy, moderately trained men in a randomized, double-blind trial. The exercise consisted of unilateral knee concentric/eccentric weight lifting with 6 sets x 10 repetitions at 80-85% of the 1 repetition maximal contraction. Muscle biopsies of each vastus lateralis (EX = exercised/REST = control) were taken 24 h after exercise for immunohistochemical staining of inflammatory cells (leukocyte common antigen). At 24 and 48 h postexercise, we also determined DOMS, plasma CK activity, and knee extensor muscle torque. RESULTS: Exercise resulted in an increased CK activity at +24 and +48 h (vs preexercise: P < 0.01), with no treatment effect. There were no treatment effects for any of the measured variables except for a return of voluntary knee extension torque to baseline by +48 h postexercise for NSAID treatment (P < 0.05). CONCLUSIONS: NSAID administration did not alter CK rise, muscle force deficit at 24 h postexercise, nor perceived muscle pain. In addition, the increased CK at 24 h postexercise was not associated with an acute myofibrillar inflammatory cell infiltrate in moderately trained men after resistance exercise.     

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.     

Breast cancer screening among women in their forties: an overview of the issues

This article summarizes the issues prompting a recent NIH Consensus Conference on mammography screening for women in their forties. To date, eight randomized controlled trials of breast cancer screening have been conducted, and a reduction in breast cancer mortality has emerged after 10 to 15 years of follow-up among women offered screening in their forties. No effect appears for at least eight years, and the reason for the delay, compared to that seen in women aged 50-69, is not clear. Two possibilities include cancer-stage shift due to screening in younger women and the aging of women into their fifties during the course of screening. Possible adverse effects of screening include radiation risk, although this is low, false-negative and false-positive screening tests, and overdiagnosis due to detection of ductal carcinoma in situ (DCIS). In order to make appropriate decisions regarding mammography, women need age-related information about both the benefits and potential risks of screening.     

Update: cancer screening in women

Current cancer screening recommendations for women have been reviewed. Controversies have been identified. Many additional references are available upon request.     

The Gothenburg breast screening trial: first results on mortality, incidence, and mode of detection for women ages 39-49 years at randomization

BACKGROUND: The effect of mammography screening on breast carcinoma mortality in women ages < 50 years remains unclear. METHODS: A randomized trial of invitation to breast carcinoma screening with mammography was performed in the city of Gothenburg, Sweden. The purpose was to estimate the effect of mammographic screening on breast carcinoma mortality in women ages < 50 years. Randomization was initially by day-of-birth cluster (18% of subjects), and subsequently by individual (82% of subjects). Between September 1983 and April 1984, 11,724 women ages 39-49 years were randomized to the study group. This group was invited to mammographic screening every 18 months. Two-view mammography was used at each screen unless the density of the breast at the previous screen indicated that single view was adequate. Fourteen thousand two hundred and seventeen women in the same age range were randomized to a control group that was not invited to undergo screening until the fifth screen of the study group (between 6 and 7 years after randomization). Women with breast carcinoma diagnosed up to the time immediately after the first screen of the control group were followed for death from breast carcinoma until the end of December 1994. RESULTS: A 45% reduction in mortality from breast carcinoma was observed in the study group compared with the control group (relative risk [RR] = 0.55, P = 0.035, 95% confidence interval [CI], 0.31-0.96). A conservative estimate based on removal of the tumors detected at the first screen of the control group gave a mortality reduction of 44% (RR = 0.56, P = 0.046, 95% CI, 0.31-0.99). In both cases, the effect was statistically significant. CONCLUSIONS: Mammographic screening can reduce mortality from breast carcinoma in women ages < 50 years. The mortality reduction can be substantial if high quality mammography is used and an 18-month interscreening interval is strictly adhered to.     

The Latina Breast Cancer Control Study, year one: factors predicting screening mammography utilization by urban Latina women in Massachusetts

The mechanisms underlying secondary or delayed cell death following traumatic brain injury (TBI) are poorly understood. Recent evidence from experimental models of TBI suggest that diffuse and widespread neuronal damage and loss is progressive and prolonged for months to years after the initial insult in selectively vulnerable regions of the cortex, hippocampus, thalamus, striatum, and subcortical nuclei. The development of new neuropathological and molecular techniques has generated new insights into the cellular and molecular sequelae of brain trauma. This paper will review the literature suggesting that alterations in intracellular calcium with resulting changes in gene expression, activation of reactive oxygen species (ROS), activation of intracellular proteases (calpains), expression of neurotrophic factors, and activation of cell death genes (apoptosis) may play a role in mediating delayed cell death after trauma. Recent data suggesting that TBI should be considered as both an inflammatory and/or a neurodegenerative disease is also presented. Further research concerning the complex molecular and neuropathological cascades following brain trauma should be conducted, as novel therapeutic strategies continue to be developed.     

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.     

Cervical cancer screening: knowledge of own screening status among women aged 20-29 years

BACKGROUND: Studies have shown that accuracy of self-reported screening for cervical cancer is not optimal. In order to improve women's knowledge of their screening status and in broader terms improve communication between patient and doctor the risk groups who require special attention with regard to information have to be identified. The purpose of this study was to identify lifestyle and socio-demographic determinants for denying screening when in fact it had been performed. METHODS: A case-control study among 7,763 women aged 20-29 years from Copenhagen. Data were obtained by means of a personal interview using a standardized questionnaire and from a computerized pathology registry. Determinants for not knowing own screening status were identified using multiple logistic regression analysis. RESULTS: In all, 13% of the women could not state correctly that they had been screened for cervical cancer. The major determinant was younger age (adjusted odds ratio: 5.8, for women aged 20-22 years compared with women aged 26-29 years). Other determinants included few Pap smears, increasing years since last Pap smear, no previous abnormal Pap smear, lower education, never having used oral contraceptives, and current smoking. CONCLUSIONS: Knowledge about own screening status is not optimal in Denmark. Our study shows that doctors have to be extra careful with information to the youngest women and to certain other groups.     

Increasing screening mammography in asymptomatic women: Evaluation of a second-generation, theory-based program.

Two theory-based programs to increase mammography screening rates among asymptomatic women were implemented and evaluated in the community. One program (E) was based on the Health Belief Model (HBM); the second program (EP) added exercises adapted from the social psychology of compliance. Program impact on screening among 295 primarily Caucasian, middle-class women was evaluated against untreated controls (C) over a 6-month period. Both programs led to increases in HBM components (Perceived Susceptibility, and Perceived Benefits) and Intentions to obtain a mammogram. Screening rates 2 to 3 times higher were observed in the EP and E over C conditions; EP and E did not differ. A mediational model of compliance illustrated the interplay of HBM components in the compliance process. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Breast cancer care in older women: sources of information, social support, and emotional health outcomes

BACKGROUND: The authors studied older women with breast cancer and asked: 1) where do older women get information regarding breast cancer care and how helpful do they perceive each of these sources to be? and 2) what aspects of social support are associated with older women's general and breast cancer specific emotional health outcomes? METHODS: To be eligible, women had to be at least 55 years of age and newly diagnosed with TNM Stage I or II breast cancer. Data were collected from women's surgical records and a 35-minute, computer-assisted telephone interview. RESULTS: Nearly all women rated information that was provided by their breast cancer physicians as very or somewhat helpful. Written materials provided by breast cancer physicians also were frequently rated as very or somewhat helpful. Women's marital status, religious service attendance, ratings of their physicians' technical and interpersonal care, and perceptions of their own abilities to communicate with their physicians were significantly associated with both general and breast cancer specific emotional health outcomes (all P < 0.05). CONCLUSIONS: Although older women obtained information regarding breast cancer from a variety of sources, they relied heavily on their physicians for information. To care most effectively for this group of patients, an increased understanding of the relation between the processes and outcomes of breast cancer care is needed Identifying older women with breast cancer at risk for poor emotional health outcomes and developing methods to enhance physician-patient communication in this setting may improve these outcomes.