Stage, age, comorbidity, and direct costs of colon, prostate, and breast cancer care.

PURPOSE: This study was conducted to evaluate the effect of stage at diagnosis, age, and level of comorbidity (presence of other illness) on the costs of treating three types of cancer among members of a health maintenance organization. METHODS: Among 388,000 members enrolled anytime during 1990 and 1991 in Group Health Cooperative (GHC) of Puget Sound (Washington State), we estimated the total and net direct costs of medical care for colon, prostate, and breast cancers, including both incident (290, 554, and 645 patients, respectively) and prevalent (1046, 1295, and 2299 patients, respectively) cases. We summarized costs for initial, continuing, and terminal phases of care. Net costs were the difference between the costs of the care of each case subject and the average costs of the care for all enrollees without the cancer of interest who were of the same sex and in the same 5-year age group. Differences in estimated total and net costs by stage at diagnosis, age, and comorbidity were separately evaluated using multivariate regression modeling. All P values were two-sided. Comorbidity was based on a score calculated from 1988 pharmacy data. RESULTS: Total costs of initial care increased with stage at diagnosis for colon (P = .0013) and breast (P < .0001) cancer cases, but not for prostate cancer cases. Total initial costs decreased with age for prostate (P = .0225) and breast (P = .0002) cancers but did not change with degree of comorbidity for any of the three cancers. Total continuing medical care costs increased with stage at diagnosis for colon (P < .0001) and breast (P < .0001) cancer cases but not for prostate cancer cases. Total terminal care costs were similar by stage for all three cancers. Net initial costs differed with stage for all three cancers (P < .05). Net continuing care costs increased with stage (P < .0001) and decreased with age (P < .001) for colon and breast cancers but not for prostate cancer. Net continuing care costs decreased with comorbidity for all three cancers (P = .004, P = .011, and P < .0001 for colon, prostate, and breast cancers, respectively). Among regional stage cancers, continuing care costs decreased with age for colon (P < .0017) and breast (P = .033) cancers but not for prostate cancers. CONCLUSIONS: The results show that total costs vary by stage at diagnosis and age, but the patterns of variation differ for each cancer. Costs of cancer are not simply additive to costs of other conditions. IMPLICATIONS: More needs to be done to explore the reasons and implications of age-related cost differences. Cost-effectiveness analyses of cancer control interventions that shift cancer stage distributions may need to consider both the age and comorbidity of the target populations.

Variation in mammographic breast density by time in menstrual cycle among women aged 40-49 years.

BACKGROUND: Mammography is less effective for women aged 40-49 years than for older women, which has led to a call for research to improve the performance of screening mammography for younger women. One factor that may influence the performance of mammography is breast density. Younger women have greater mammographic breast density on average, and increased breast density increases the likelihood of false-negative and false-positive mammograms. We investigated whether breast density varies according to time in a woman's menstrual cycle. METHODS: Premenopausal women aged 40-49 years who were not on exogenous hormones and who had a screening mammogram at a large health maintenance organization during 1996 were studied (n = 2591). Time in the menstrual cycle was based on the woman's self-reported last menstrual bleeding and usual cycle length. RESULTS: A smaller proportion of women had "extremely dense" breasts during the follicular phase of their menstrual cycle (24% for week 1 and 23% for week 2) than during the luteal phase (28% for both weeks 3 and 4) (two-sided P = .04 for the difference in breast density between the phases, adjusted for body mass index). The relationship was stronger for women whose body mass index was less than or equal to the median (two-sided P<.01), the group who have the greatest breast density. CONCLUSIONS/IMPLICATIONS: These findings are consistent with previous evidence suggesting that scheduling a woman's mammogram during the follicular phase (first and second week) of her menstrual cycle instead of during the luteal phase (third and fourth week) may improve the accuracy of mammography for premenopausal women in their forties. Breast tissue is less radiographically dense in the follicular phase than in the luteal phase.

Breast density as a predictor of mammographic detection: comparison of interval- and screen-detected cancers.

BACKGROUND: Screening mammography is the best method to reduce mortality from breast cancer, yet some breast cancers cannot be detected by mammography. Cancers diagnosed after a negative mammogram are known as interval cancers. This study investigated whether mammographic breast density is related to the risk of interval cancer. METHODS: Subjects were selected from women participating in mammographic screening from 1988 through 1993 in a large health maintenance organization based in Seattle, WA. Women were eligible for the study if they had been diagnosed with a first primary invasive breast cancer within 24 months of a screening mammogram and before a subsequent one. Interval cancer case subjects (n = 149) were women whose breast cancer occurred after a negative or benign mammographic assessment. Screen-detected control subjects (n = 388) were diagnosed after a positive screening mammogram. One radiologist, who was blinded to cancer status, assessed breast density by use of the American College of Radiology Breast Imaging Reporting and Data System. RESULTS: Mammographic sensitivity (i.e., the ability of mammography to detect a cancer) was 80% among women with predominantly fatty breasts but just 30% in women with extremely dense breasts. The odds ratio (OR) for interval cancer among women with extremely dense breasts was 6.14 (95% confidence interval [CI] = 1.95-19.4), compared with women with extremely fatty breasts, after adjustment for age at index mammogram, menopausal status, use of hormone replacement therapy, and body mass index. When only those interval cancer cases confirmed by retrospective review of index mammograms were considered, the OR increased to 9.47 (95% CI = 2.78-32.3). CONCLUSION: Mammographic breast density appears to be a major risk factor for interval cancer.

Breast tumor characteristics as predictors of mammographic detection: comparison of interval- and screen-detected cancers.

BACKGROUND: Although mammographic screening is useful for detecting early breast cancer, some tumors are detected in the interval between screening examinations. This study attempted to characterize fully the tumors detected in the two different manners. METHODS: Our study utilized a case-control design and involved a cohort of women undergoing mammographic screening within the defined population of a health maintenance organization (the Group Health Cooperative of Puget Sound). Women were classified as having "interval" or "interval-detected" cancers (n = 150) if their diagnosis was made within 24 months after a negative-screening mammogram or one that indicated a benign condition. Cancers were classified as "screen detected" (n = 279) if the diagnosis occurred after a positive assessment by screening mammography. Tumors from women in each group were evaluated for clinical presentation, histology, proliferative characteristics, and expression of hormone receptors, p53 tumor suppressor protein, and c-erbB-2 protein. RESULTS: Interval-detected cancers occurred more in younger women and were of larger tumor size than screen-detected cancers. In unconditional logistic regression models adjusted for age and tumor size, tumors with lobular (odds ratio [OR] = 1.9; 95% confidence interval [CI] = 0.9-4.2) or mucinous (OR = 5.5; 95% CI = 1.5-19.4) histology, high proliferation (by either mitotic count [OR = 2.9; 95% CI = 1.5-5.7] or Ki-67 antigen expression [OR = 2.3; 95% CI = 1.3-4.1]), high histologic grade (OR = 2.1; 95% CI = 1.2-4.0), high nuclear grade (OR = 2.0; 95% CI = 1.0-3.7), or negative estrogen receptor status (OR = 1.8; 95% CI = 1.0-3.1) were more likely to surface in the interval between screening examinations. Tumors with tubular histology (OR = 0.2; 95% CI = 0.0-0.8) or with a high percentage of in situ components (50%) (OR = 0.5; 95% CI = 0.2-1.2) were associated with an increased likelihood of screen detection. CONCLUSIONS: Our data from a large group of women in a defined population indicate that screening mammography may miss tumors of lobular or mucinous histology and some rapidly proliferating, high-grade tumors.

Mammography diffusion and trends in late-stage breast cancer: evaluating outcomes in a population.

The purpose of this study was to assess mammography diffusion in a population offered an organized breast cancer screening program, using intervals of 1-3 years, and to evaluate its effect on the late-stage cancer (tumors > or = 3 cm2) rates compared to rates in the surrounding community. We measured "ever-use" of mammography (1986-1992) among women enrollees of a consumer-controlled health care organization (n > or = 60,000/year; ages > or = 40), Group Health Cooperative of Puget Sound (GHC). Among these same women and the surrounding community (n = > or = 745,000/year), we measured late-stage cancer rates. Using unconditional logistic regression, we compared annual rates of ever-use among GHC women ages 40-49 and > or = 50 (1986-1992) and late-stage breast cancer (1983/84-1991/92) among all women. Among all GHC women ages 40 to 49, and 50 years of age and older, 67.4 and 82.8%, respectively, ever-used mammography by 1992. By 1992, approximately one-third of the mammograms among GHC women occurred in each of the three previous years. The rate of late-stage tumors declined significantly in the GHC and non-GHC populations among women 50 years of age and older (P < 0.001) but not among women ages 40 to 49. In conclusion, implementing a system of automated reminders was not sufficient to maximize mammography use in a population. Reductions in late-stage disease occurred among women ages > or = 50, even when regular" was not synonymous with "annual."

The association of human papillomavirus antibodies with cervical cancer risk.

The association between viral human papillomavirus (HPV) DNA and cervical carcinoma has been well documented. However, less is known about the immune response to HPV infections and its relationship to cervical cancer risk. A higher prevalence of antibodies to HPV16 E7 among women with cervical cancer compared with controls has been reported, but reactivity to other antigens has not been systematically examined. Prevalence of serum IgG antibody reactivities to HPV6-encoded L1 and L2 and to HPV16- and HPV18-encoded E2, E4, E6, E7, L1, and L2 bacterial fusion proteins in a Western immunoblot assay were measured among cases with invasive cervical cancer (n = 69) and control women (n = 81). The intensities of the Western blot bands were graded as +1, +2, or +3 (0 = negative). Antibodies to HPV6 L1 and L2, HPV16 E7 and L2, and HPV18 L2 fusion proteins were observed among 39-62% of cases and 33-71% of controls. After systematic sampling for antibody reactivity to this range of fusion proteins, the sample was expanded to include 150 cases and 145 controls tested exclusively for reaction to HPV6 L1 and L2, HPV16 E7, and HPV16 and HPV18 L2. Relative risk was estimated for > or = +1, +1, and > or = +2 levels of reactivity after adjustment for confounding factors. Except for HPV16 E7, reactivity at the > or = +1 level did not distinguish cases from controls.(ABSTRACT TRUNCATED AT 250 WORDS)

The relationship of human papillomavirus-related cervical tumors to cigarette smoking, oral contraceptive use, and prior herpes simplex virus type 2 infection.

It has now been established that infection with human papillomavirus (HPV) is necessary for the development of most cervical cancers. HPV is not sufficient for the development of cancer. Other exposures or host factors are necessary for cancer to occur. As part of an ongoing, population-based case-control study of invasive cervical cancer, we investigated the role of cigarette smoking, oral contraceptive (OC) use, and herpes simplex virus type 2 (HSV-2) as potential cofactors with HPV in the development of cervical cancer. Residents of three counties in western Washington State who were diagnosed with invasive squamous cell cervical cancer (n = 314) from January 1986 through December 1992 were interviewed about their sexual, reproductive, contraceptive, and cigarette smoking histories. Similar information was obtained from control women identified through random digit dialing (n = 672). The sera from 206 cases and 522 controls were tested for both HPV 16 capsid antibodies and HSV-2 antibodies. PCR was used to test paraffin-embedded tumor tissues for the presence of HPV DNA types 6, 16, 18, 31, 33, 35, and 39. Women with cervical cancer were more likely to be current smokers at diagnosis than population controls [relative risk (RR), 2.5; 95% confidence interval (CI), 1.8-3.4]. The risk associated with smoking was present to a similar extent among women positive and negative for HPV as measured by HPV 16 capsid antibodies and HPV DNA in the tumor tissue (cases). OC use was only important if first use was at an early age, particularly ages < or = 17 years (RR, 2.3; 95% CI, 1.4-3.8). There was only a slight risk for cervical cancer associated with antibodies to HSV-2 (RR, 1.2; 95% CI, 0.9-1.7). However, when we stratified by markers of HPV exposure, we found a significant increase in risk associated with HSV-2 among women negative for HPV 16 antibodies (RR, 2.0; 95% CI, 1.3-3.0), which was strengthened when we confined our analysis to cases whose tumors were HPV DNA negative (RR, 3.6; 95% CI, 1.6-8.0). There was no indication that cigarette smoking, OC use, or HSV-2 infection influence the ability of HPV infection to cause invasive cervical cancer. OC use may only be important in the etiology of invasive squamous cell cervical tumors if the use occurs at a critical time in the development of a woman's reproductive tract, at ages < or = 17 years. The majority of risk associated with HSV-2 was confined to HPV-negative tumors, indicating a possible separate pathway to disease that may account for 5-10% of invasive cervical cancers.

Variation in mammographic breast density by race.

PURPOSE: Because of the observed racial differences in risk of developing breast cancer, the authors conducted a study to determine the variation in breast density, a strong predictor of breast cancer risk, by race and age. METHODS: Study subjects were women enrolled in Group Health Cooperative of Puget Sound, Seattle, WA, aged 20-79 years, who had a screening mammogram between 6/1/96 and 8/1/97. Women with increased breast density (BI-RADS "heterogeneously dense" and "extremely dense") (n = 14,178) were compared to those with fatty breasts (BI-RADS "almost entirely fat" and "scattered fibroglandular tissue") (n = 14,323). Logistic regression was used with adjustment for age, parity, age at first birth, menopausal status, current use of hormone replacement therapy, and body mass index. RESULTS: The odds ratio (OR) for having dense breasts versus fatty breasts, comparing Asian to White women, increased from 1.2 [95% confidence interval (CI) 0.9-1.6] for women age <45 to 1.6 (95% CI 1.3-2.2) for women over 65. Conversely, the OR for Black compared to White women was highest for the women age 65 and younger (OR 1.7 (1.2-2.3), 1.3(1.0-1.7), and 1.7 (1.2-2.3) for women age <45, 46-55, and 56-65, respectively), whereas Black women over 65 had similar density as Whites. Hispanic women had similar density compared to Whites for all ages. CONCLUSIONS: These racial differences in breast density generally do not conform to differences in race and age-specific breast cancer incidence rates.

Cancer screening in HMOs: program development and evaluation.

INTRODUCTION: In many clinical settings, effective cancer control is hampered by barriers related to the acute-care orientation of most medical practices. These include: prioritization of medical problems on the basis of urgency; a problem-oriented medical record that provides no ongoing documentation mechanism for cancer screening; conflicting guidelines; and no method for identifying and targeting persons who are eligible for screening. In contrast, HMOs are uniquely suited to deliver effective cancer control as they have already established many of the linkages required for successful primary and secondary prevention. METHODS: This paper describes the principles of a population-based approach to cancer prevention and draws on the experience of Group Health Cooperative of Puget Sound, an HMO in western Washington with more than 20 years' experience in prevention and centralized cancer screening. Methods for selecting and determining priorities among cancer prevention issues, components of successful screening programs, and measures of short- and long-term evaluation are discussed through examples of screening for breast, prostate, cervix, and colorectal cancers. CONCLUSIONS: HMOs have provided leadership in the integration of health services and the promotion of continuity of care. Using a population-based approach, cancer prevention programs may be supported by existing automated information services to reduce morbidity and mortality through early detection.

Prostate-specific antigen for prostate cancer screening. Do physician characteristics affect its use?

PURPOSE: Screening for prostate cancer with the prostate-specific antigen (PSA) test remains controversial. This controversy is reflected in a lack of consensus in the medical literature and among professional and policy organizations regarding routine screening by PSA. It is not known how physicians respond when recommendations from experts are inconsistent. METHODS: A questionnaire was mailed to 1369 primary care physicians in active practice in Washington State in 1994. Response rate to the survey was 63%. Chi-square tests and multivariate logistic regression analysis were used to examine the effects of physician characteristics on physicians' self report of use of the PSA test for screening asymptomatic male patients, aged 50 to 80, for prostate cancer. RESULTS: Of the 714 physicians included in the analysis, 68% reported routine use of PSA. Use of PSA varied among physicians on the basis of practice setting, years since medical school graduation, and whether compensation was fee-for-service or salaried. Male physicians trained before 1974 and physicians receiving fee-for-service were significantly more likely than other physicians to recommend screening by PSA. CONCLUSIONS: Results suggest that physicians' personal characteristics such as year of medical school graduation, gender, and mode of reimbursement are related to self-reported PSA use.

Colorectal cancer screening participation by older women.

OBJECTIVE: Although recent screening guidelines recommend annual fecal occult blood testing (FOBT) for adults aged > or = 50, a number of studies report that these tests are underused. Systematic efforts to increase awareness of colorectal cancer (CRC) and to promote screening participation are needed to meet national objectives for CRC control. METHODS: This study examined CRC-screening practices and evaluated factors related to recent participation in screening by FOBT in a sample of women aged 50 to 80 who were surveyed about their use of clinical preventive services at Group Health Cooperative, a managed care organization in western Washington State. RESULTS: Of the 931 women eligible for analysis, 75% reported ever having been screened by FOBT and 48% reported having been screened within 2 years before the survey. Participation in screening did not vary by demographic characteristics or by perceived or actual risk of CRC. Women with a positive attitudes toward CRC screening had sevenfold greater odds of recent screening by FOBT (odds ratio=7.1; 95% confidence interval, 4.4 to 11.6). Only 58% of study women reported that their physicians encouraged CRC screening, but this factor was strongly related to participation (odds ratio=12.7; 95% confidence interval, 6.6 to 24.4). CONCLUSIONS: We identified several areas in which understanding of CRC risk may be low. As a whole, these findings suggest that effective strategies to control CRC may include efforts to improve knowledge of risk and prevention, but must also appeal directly to primary care physicians to identify and address their barriers to screening recommendations.

Does provider prevention orientation influence female patients' preventive practices?

BACKGROUND: Health care provider encouragement for particular preventive behaviors is associated with patient adherence, but it is unclear whether a provider's overall prevention approach influences whether patients engage in recommended preventive measures. We examined whether older women who perceived that their health care provider encouraged a particular preventive behavior were more likely to follow that recommendation if they also perceived that the provider encouraged other preventive behaviors. DATA AND METHODS: The sample included 1119 women aged 50 to 79 enrolled in a health maintenance organization. We examined associations of reported provider encouragement for post-menopausal hormone use, physical activity, fecal occult blood testing (FOBT), and flexible sigmoidoscopy with one another and with adherence to these measures according to recommended guidelines. RESULTS: Among women reporting provider encouragement for physical activity, the likelihood of reporting regular physical activity was greater among women who reported encouragement for one other (odds ratio [OR]=1.99; confidence interval [CI]=1.35 to 2.95) and at least two other (OR=2. 38; 95% CI=1.62 to 3.48) preventive measures compared with women who reported no other encouragement. The likelihood of reporting adequate counseling for post-menopausal hormone use was greater among women reporting encouragement for at least two other preventive measures compared with those reporting no other encouragement. The likelihood of having had an FOBT or sigmoidoscopic examination was related to encouragement for those procedures, but not with greater encouragement for other preventive measures. CONCLUSIONS: Patient perceptions of a provider's overall preventive practice approach may influence whether patients engage in recommended preventive practices, particularly for lifestyle factors.

Principles of cancer screening for clinicians.

This chapter has outlined some principles of tumor growth, test characteristics, and the evaluation of screening technologies. We have emphasized that test specificity is the critical parameter in the evaluation of technologies because it is the healthy people who will suffer the most from the adverse effects of screening. We have also emphasized that the efficacy of a test is best evaluated by examining mortality reductions in comparable populations. The purpose has been to assist clinicians with their interpretation of the literature. Busy clinicians may not always have the time or inclination to do this themselves. In those cases they need to examine how organizations who make recommendations are coming to their conclusions because it is physicians, not organizations that will do the screening. In particular, it is important to ask the following: (1) Were criteria followed to justify the recommendations being made? (2) If so, what were they, and can the organization demonstrate that they are being met? (3) What perspectives and biases do the organizations bring to the judgments they inevitably have to make? (4) Do you share those perspectives? and (5) When the recommendation is adopted, can you guarantee that it will "first do no harm."

Use of antidepressant medications in relation to the incidence of breast cancer.

Although associations have been reported between antidepressant use and risk of breast cancer, the findings have been inconsistent. We conducted a population-based case-control study among women enrolled in Group Health Cooperative (GHC), a health maintenance organization in Washington State. Women with a first primary breast cancer diagnosed between 1990 and 2001 were identified (N = 2904) and five controls were selected for each case (N = 14396). Information on antidepressant use was ascertained through the GHC pharmacy database and on breast cancer risk factors and screening mammograms from GHC records. Prior to one year before diagnosis of breast cancer, about 20% of cases and controls had used tricyclic antidepressants (adjusted odds ratio = 1.06, 95% CI 0.94-1.19) and 6% of each group had used selective serotonin reuptake inhibitors (OR = 0.98, 95% CI 0.80-1.18). There also were no differences between cases and controls with regard to the number of prescriptions filled or the timing of use. Taken as a whole, the results from this and other studies to date do not indicate an altered risk of breast cancer associated with the use of antidepressants overall, by class, or for individual antidepressants.

A record-based evaluation of induced abortion and breast cancer risk (United States).

OBJECTIVE: Previous studies of induced abortion and breast cancer may have been limited by differential reporting of abortion history. We conducted a population-based case-control study to evaluate abortion (both induced and spontaneous) and breast cancer risk. METHODS: All study subjects were aged 20-69 years and members of Group Health Cooperative of Puget Sound (GHC). Incident invasive breast cancer cases (n = 138) were identified from the linkage between the GHC enrollment file and the Seattle-Puget Sound SEER Cancer Registry. Controls (n = 252) were randomly selected from GHC enrollment files and matched to cases on age and enrollment period. All subjects had to have been enrolled at GHC for the 2 years preceding diagnosis (cases) or reference (controls) date. The unified medical record of each case was abstracted for pregnancy history, including prior induced and spontaneous abortions, menopause status, height and weight, screening practices, and other risk factors. RESULTS: Compared to all women who had never had an induced abortion, the multivariate adjusted relative risk of breast cancer in women with an induced abortion was 0.9 (95% confidence interval 0.5-1.6). This risk was similar in parous women, and nulliparous women. There was no association between spontaneous abortion and breast cancer risk. CONCLUSIONS: These results do not support a relation between induced abortion and breast cancer incidence.

Low birth weight in relation to multiple induced abortions.

BACKGROUND: Most studies report that a single induced abortion does not increase risk for delivering a low birth weight infant in a subsequent pregnancy. However, the effect of multiple abortions has not been adequately evaluated. METHODS: This relationship was studied in 6541 White women who delivered their first child between 1984 and 1987. We compared the frequencies of low birth weight (less than 2500 g) among infants born to 1999 women without prior induced abortion and 1999 women with one abortion with the frequencies of low birth weight among infants born to women with two (n = 1850), three (n = 520), and four or more (n = 173) prior induced abortions. RESULTS: After adjustment for confounding variables, we found no linear relationship in risk of low birth weight among women with one (relative risk [RR] = 1.2, 95% confidence interval [CI] = 0.9-1.5), two (RR = 1.5, 95% CI = 1.1-2.0), three (RR = 1.3, 95% CI = 0.8-1.9), or four or more (RR = 1.6, 95% CI = 0.9-2.9) prior induced abortions. CONCLUSIONS: These findings confirm earlier reports of little or no evidence of harmful effects on birth weight by one or by two or more induced abortions. We further report that risk is not significantly elevated even in women with three, four, or more prior terminations of pregnancy when compared with women with one or two abortions.

PSA screening: a public health dilemma.

Screening for prostate cancer with serum prostate specific antigen (PSA) is one of the most controversial practices in health care today and guidelines from professional and policy organizations are contradictory. Prostate cancer is unique because of a wide discrepancy between prevalent asymptomatic cancer and clinical disease and an uncertain natural history. Proponents and critics of mass screening agree that PSA can detect early cancer and that definitive data that PSA reduces prostat cancer mortality are not available. Differences in screening recommendations reflect distinct viewpoints regarding what constitutes screening benefit and what level of evidence is needed to endorse a screening practice. This review describes what is known about the areas most relevant to the conflicting perspectives: the epidemiology and natural history of prostate cancer, the ability of PSA to detect disease and operational characteristics of PSA as a screening test, and the efficacy of treatment of early disease.

Reproductive and hormonal factors associated with mammographic breast density by age (United States).

OBJECTIVES: We determined the association of certain reproductive and hormonal factors with breast density over decades of life. METHODS: Subjects were women age 20-79 years who had a screening mammogram between 1 June 1996 and 1 August 1997, in Seattle, Washington. Women with increased breast density (upper two categories of BI-RADS terminology) (n = 14,432) were compared to those with fatty breasts (lower two categories (n = 14,552). Unconditional logistic regression was used with adjustment for age at mammogram, parity, age at first birth, menopausal status, current use of hormone replacement therapy (HRT), and body mass index. RESULTS: The association of nulliparity with density was evident for women at all ages (odds ratio (OR) and 95% confidence interval (CI) = 1.5 (1.3-1.7) and 1.6 (1.4-1.9) for women age < or = 45 and > 65, respectively). Older age at first birth was more strongly associated with density among women > 55 than among younger women. The association of current use of HRT with density, but not of former use, increased with age when compared to never users (OR = 1.4 (1.2-1.7) and 2.2 (2.0-2.5) for women age 46-55 and > 65, respectively). CONCLUSIONS: Results suggest that pregnancy at an early age has a permanent beneficial association with density, while HRT has a transitory adverse association.

Changes in breast density associated with initiation, discontinuation, and continuing use of hormone replacement therapy.

CONTEXT: Initiation of hormone replacement therapy (HRT) has been shown to increase breast density. Evidence exists that increased breast density decreases mammographic sensitivity. The effects on breast density of discontinuing and continuing HRT have not been studied systematically. OBJECTIVE: To examine the effects of initiation, discontinuation, and continued use of HRT on breast density in postmenopausal women. DESIGN, SETTING, AND PARTICIPANTS: Observational cohort study of 5212 naturally postmenopausal women aged 40 to 96 years and enrolled in a large health maintenance organization in western Washington State who had 2 screening mammograms between 1996 and 1998. MAIN OUTCOME MEASURES: Breast density, assessed using the clinical radiologists' BI-RADS 4-point scale, compared among women who did not use HRT before either mammogram (nonusers); who used HRT before the first but not before the second mammogram (discontinuers); who used HRT before the second but not before the first mammogram (initiators); and who used HRT prior to both mammograms (continuing users). RESULTS: Relative to nonusers, women who initiated HRT were more likely to show increases in breast density (relative risk [RR], 2.57; 95% confidence interval [CI], 2.12-3.08), while women who discontinued HRT use were more likely to show decreases in density (RR, 1.81; 95% CI, 1.06-2.98) and women who continued to use HRT were more likely to show both increases in density (RR, 1.33; 95% CI, 1.13-1.55) and sustained high density (RR, 1.45; 95% CI, 1.33-1.58). CONCLUSIONS: These results indicate that breast density changes associated with HRT are dynamic, increasing with initiation, and decreasing with discontinuation.

Primary and secondary prevention services in clinical practice. Twenty years' experience in development, implementation, and evaluation.

This article reviews lessons from 20 years of experience in development and provision of clinical preventive services at Group Health Cooperative of Puget Sound, a large health maintenance organization. Critical factors for enhancing service include the use of a population-based epidemiologic viewpoint coupled with specific evidence-based criteria to examine issues; involvement of practitioners in the process; a systems approach to implementation focused on predisposing factors of the practitioners and enabling factors in the practice, organizational, and community environments; feedback of program outcomes; and the use of automated clinical information systems. Outcome results from our clinical prevention efforts include a 32% decrease in late-stage breast cancer (1989 to 1990); 89% of 2-year-old children with complete immunizations (1994); decrease in adult smokers from 25% to 17% (1985 to 1994); and an increase in bicycle safety helmet use among children from 4% to 48% along with a 67% decrease in bicycle-related head injuries (1987 to 1992). Systematic population-based approaches to the development and provision of clinical preventive services targeting the one-to-one level of primary care and multiple infrastructure levels of care are forging a synthesis of clinical medicine and public health approaches. This approach will become pervasive as clinical information systems improve, risk information is captured routinely, and practitioners gain skills in the art of patient risk behavior change and population-based care.