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The daily administered dose of progestin in continuous-combined estrogen-progestin therapy is provided to counteract the proliferative effect of estrogen on the postmenopausal endometrium. However, there remains some uncertainty as to whether use of such a combined regimen, over the long term, is associated with an altered risk of endometrial cancer. We pooled data from four population-based case-control studies of endometrial cancer in western Washington State. Cases, ages 45-74, were diagnosed between 1985 and 2005. Using logistic regression with the adjustment for confounding factors, women who had exclusively used continuous-combined estrogen-progestin therapy (90 endometrial cancer cases, 227 controls) were compared with women who had never used any type of hormone therapy (774 cases, 1,116 controls). Associations with duration and recency of use were evaluated overall and within strata defined by body mass index. Long-term use of continuous-combined estrogen-progestin therapy (≥10 years) was associated with a reduced risk of endometrial cancer (OR = 0.37, 95% CI: 0.21-0.66). This association was most pronounced in women with a body mass index ≥30 kg/m(2) (OR = 0.19, 95% CI: 0.05-0.68). Associations did not differ according to recency of use. These results suggest that long duration of use of continuous-combined estrogen-progestin therapy is associated with a reduced risk of endometrial cancer.

As part of a prospective case-control study of newly diagnosed rheumatoid arthritis (RA) in women, we identified all cases of probable, definite, or classic RA diagnosed in 1987-1989 in 18-64-year-old women who were members of a health maintenance organization based in the Seattle, Washington area. Using both the 1958 and the 1987 American Rheumatism Association criteria for the diagnosis of RA and enrollment data from the health maintenance organization, we calculated the incidence by age and diagnostic class. Rates of RA incidence in women increased steadily with age. The incidence of probable, definite, or classic RA ranged from 13.1 per 100,000 person-years at risk for 18-29-year-old women to 82.1 per 100,000 person-years for 60-64-year-old women. The overall incidence rate, age-adjusted to the 1980 US female population, was 27.9/100,000 person-years. The overall incidence rate for definite/classic RA, age-adjusted to the 1980 US female population, was 23.9 per 100,000 person-years. When compared with adjusted rates of incidence of definite RA in Rochester, Minnesota, in 1950-1974, the incidence rates we found were 44.7% lower. Methodologic differences, changes in diagnostic criteria, and a declining incidence of RA among women over time may all be partial explanations for these results. The possible effects of reproductive factors, including oral contraceptives use, are discussed.

Limited data exist to inform clinicians and patients as to the likelihood of long-term endometrial hyperplasia response to progestin therapy, especially for atypical hyperplasia. We evaluated women with complex and atypical endometrial hyperplasia, comparing those prescribed progestin with those not prescribed progestin.This retrospective cohort study was conducted in 1985-2005 among women aged 18-88 years at an integrated health plan in Washington State. Women were ineligible if they achieved an outcome (endometrial carcinoma, hysterectomy, or both) within 8 weeks of hyperplasia diagnosis. Exposure was progestin use for at least 14 days by duration and recency. Outcomes included rate of 1) endometrial carcinoma, 2) hysterectomy, or 3) both. Analyses performed included Kaplan-Meier, incident rate ratios, and Cox proportional hazard ratios.One thousand four hundred forty-three eligible women were identified. One thousand two hundred one had complex (n=164 no progestin) and 242 had atypical (n=62 no progestin) hyperplasia. During follow-up, a median of 5.3 years (range 8 weeks to 20.8 years), 71 women were diagnosed with endometrial carcinoma (35 complex, 36 atypia) and 323 underwent hysterectomy (216 complex, 107 atypia). Among women with complex and atypical hyperplasia, rates of endometrial carcinoma among progestin users were 3.6 and 20.5 per 1,000 woman-years, respectively (compared with women who did not use progestin, 10.8 and 101.4). Among women with complex and atypical hyperplasia, rates of hysterectomy among progestin users were 23.3 and 61.4 per 1,000 woman-years, respectively (compared with women who did not use progestin, 55.1 and 297.3).Endometrial carcinoma risk is diminished approximately threefold to fivefold in women diagnosed with complex or atypical endometrial hyperplasia and dispensed progestin; hysterectomy risk is also decreased.II.

To document incidence rates of vulvar cancer, specifically invasive vulvar cancer, from 1973 to 2004 in the United States.Nine US cancer registries from the Surveillance, Epidemiology, and End Results (SEER) databases were used to identify women aged 15-84 years, who were first diagnosed with vulvar cancer during 1973-2004. Age-adjusted incidence rates and annual percentage changes were calculated for different time periods, stage of the disease, age, race, and geographic area.During 1973-2004, the incidence of in situ vulvar tumors increased by an average of 3.5% per year (95% CI: 2.9%, 4.1%), while the incidence of invasive tumors increased 1.0% per year (95% CI: 0.6%, 1.4%). An increasing incidence was observed for localized and regional invasive tumors. To at least some degree, the rise of incidence rates of incidence tumors was evident in every age category, race, and geographic region.Incidence rates of invasive vulvar cancer have increased in the United States during the last three decades. The reasons for this increase are unknown.

Purpose We sought to examine the relationship between recent use of oral contraceptives and hormone therapy and endometrial hyperplasia (EH) risk. Methods Cases comprised women diagnosed with complex EH ( n = 289) or atypical EH ( n = 173) between 1985 and 2003. One age-matched control was selected for each case; excluded were women with a prior hysterectomy or diagnosis of EH or endometrial cancer. Hormone use in the 6 months prior to the date of the case's first symptoms was ascertained using a pharmacy database and medical records. Odds ratios (OR) and 95% confidence intervals (CI) were calculated. Results Three (1.1%) cases had used oral contraceptives, compared to 16 (6.0%) controls (OR = 0.2, 95% CI: 0.0–0.6). Fifty-one (16.8%) cases had taken estrogen-only hormone therapy, in contrast to two (0.7%) controls (OR = 37.6, 95% CI: 8.8–160.0). The risk of EH among estrogen plus progestin hormone users did not differ from that of non-users (OR = 0.7, 95% CI: 0.4–1.1). Conclusions This study suggests that previous findings of the association of estrogen-only hormone therapy with increased risk of EH and the lack of an association between estrogen plus progestin hormone therapy and EH risk are likely to apply to both complex EH and atypical EH. Further examination of the association between oral contraceptives and EH, with greater numbers of OC users, is warranted.

Current World Health Organization classification of endometrial hyperplasia is problematic because of poor diagnostic reproducibility. We sought to determine factors that cause diagnostic disagreement in a review of 2601 endometrial specimens. Blinded random specimens of normal endometrium, hyperplasias, and carcinoma were reviewed by 2 pathologists, with review by a third pathologist in cases with disagreement. All cases of endometrial hyperplasia or carcinoma were scored for degree of glandular crowding, architectural complexity, and cytologic atypia. Sample adequacy, hyperplasia volume, presence of metaplasia, or endometrial polyp were also scored. The overall kappa for agreement was 0.71, with a lower kappa of 0.36 when cases called "no hyperplasia" were excluded. The percent specific agreement was 90.3% for no hyperplasia, 31.1% for simple hyperplasia, 51.1% for complex hyperplasia, 49.8% for atypical hyperplasia, and 57.5% for adenocarcinoma. Cases categorized as "low volume hyperplasia" had more diagnostic disagreement than "high volume," (62% vs. 39%, P=0.003). Similarly, cases called "scant" had more diagnostic disagreement than "not scant" (65% vs. 57%, P=0.013). The histologic feature associated with the most diagnostic disagreement was cytologic atypia (P

Exposure to estrogens is a likely cause of endometrial cancer, but the means by which estrogens exert this effect are not entirely clear. One hypothesis is that certain estrogen metabolites bind to the DNA, forming bulky adducts that damage the DNA and initiate carcinogenesis. A woman's reduced capacity to repair such damage may increase her risk of endometrial cancer. We conducted a population-based case-control study in western Washington State to address the role of variation in nucleotide excision repair genes on the risk of endometrial cancer. Case women (n = 371), ages 50 to 69 years, were diagnosed with invasive endometrial cancer between 1994 and 1999. Control women (n = 420) were selected using random-digit dialing (ages 50-65 years) and by random selection from Health Care Financing Administration data files (ages 66-69 years). Genotyping assays were done for ERCC1, ERCC2 (XPD), ERCC4 (XPF), ERCC5 (XPG), XPA, and XPC. No appreciable differences between cases and controls were observed in the genotype distributions of ERCC1 (c8092a and c19007t), ERCC2 (D312N, K751Q, and c22541a), ERCC4 (R415Q and t30028c), or ERCC5 (D1104H). Carriage of at least one variant allele for XPA G23A was associated with decreased risk of endometrial cancer [odds ratio (OR), 0.70; 95% confidence interval (95% CI), 0.53-0.93]. Carriage of at least one XPC A499V variant allele was associated with a modest decrease in risk (OR, 0.79; 95% CI, 0.59-1.05). Women with variant alleles at both XPC A499V and K939Q had 58% of the risk of women with no XPC variant alleles (OR, 0.58; 95% CI, 0.35-0.96). Our data suggest that interindividual variation in XPA and XPC influences a woman's risk of endometrial cancer.

2-Hydroxylated metabolites of estrogen have been shown to have antiangiogenic effects and inhibit tumor cell proliferation, whereas 4-hydroxylated metabolites have been implicated in carcinogenesis. We examined whether polymorphisms in certain genes involved in estrogen metabolism are associated with endometrial cancer risk in a population-based case-control study with 371 cases and 420 controls. Based on previously published genotype-phenotype correlation studies, we defined variant alleles thought to increase estrogen 2-hydroxylation as presumptively low-risk (CYP1A1 m1 T6235C and m2 Ile462Val) and those thought to increase estrogen 4-hydroxylation as high-risk (CYP1A1 m4 Thr461Asn, CYP1A2 A734C, and CYP1B1 Leu432Val). Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated using unconditional logistic regression. Carrying at least one CYP1A1 m1 or m2 variant allele was associated with a decreased risk of endometrial cancer [ORs (95% CIs), 0.64 (0.44-0.93) and 0.54 (0.30-0.99), respectively]. No strong alteration in risk was observed among women with any of the putative high-risk alleles. When CYP1A1, CYP1A2, and CYP1B1 genotypes were combined and ranked by the number of putative low-risk genotypes carried, women with four or five low-risk genotypes had a reduced risk of endometrial cancer (OR, 0.29; 95% CI, 0.15-0.56) compared with women with one or none. No appreciable alteration in risk was observed among women carrying two or three low-risk genotypes. Some of our findings are consistent with the hypothesis that increased estrogen 2-hydroxylation is associated with decreased endometrial cancer risk, but replication of these results is required before any firm conclusions can be reached.

Progestogens are given to diminish the risk of endometrial cancer (ECA) observed with postmenopausal estrogen therapy. The pattern of progestogen administration and number of days that the progestogen is given per month appear to affect ECA risk. We studied the impact of dose of progestogen, specifically medroxyprogesterone acetate (MPA), on ECA risk in a population-based case control study of 647 cases and 1,209 controls, ages 45–74 years. Among women who took a combined hormone regimen with MPA for less than 10 days/mo, the overall adjusted risk of ECA (relative to that of hormone non-users) was 4.2 [95%, Confidence Interval (CI) 2.0, 8.9] in those with an MPA dose less than 70 mg/mo; and the adjusted risk of ECA was 2.8 (95%, CI 0.9, 8.6) in those with a higher monthly MPA dose. Among women who took MPA cyclically for 10–24 days/mo or as continuous combined therapy, the risk of ECA was similar to non-users, irrespective of the monthly dose. Our findings showed that among the combined hormone regimens most commonly used by postmenopausal women in the USA today, monthly dose of MPA bears little or no relation to risk of ECA.

BACKGROUND There have been several epidemiologic studies investigating the association between circulating levels of insulin-like growth factor I (IGF-I), insulin-like growth factor binding protein 3 (IGFBP-3), and insulin in relation to the risk of prostate carcinoma, with conflicting results. To examine this issue further, the authors conducted a nested case–control study within the Cardiovascular Health Study cohort. METHODS In men who were diagnosed with prostate carcinoma (cases) between 1990 and 1999 (n = 174), the levels of IGF-I, IGFBP-3, and insulin were measured on blood samples that were obtained 1–9 years prior to diagnosis (mean, 3.4 years). Similar measurements were made on 174 male participants without prostate carcinoma (controls) who were matched to cases based on the year blood was drawn, survival until the date of diagnosis, race, and age. RESULTS Relative to the men with IGF-I levels in the first (lowest) quartile of the distribution, the risk of prostate carcinoma for men in the second, third, and fourth (upper) quartiles were 0.77 (95% confidence interval [95% CI], 0.43–1.38), 0.73 (95% CI, 0.41–1.30), and 0.67 (95% CI, 0.37–1.25), respectively. The results were influenced little by adjustment for levels of IGFBP-3 or, instead, by evaluating the molar IGF-I/IGFBP-3 ratio. An analysis that was restricted to men who had plasma prostate-specific antigen levels < 4 ng/mL at the time of the blood draw yielded similar results. The corresponding relative risks for IGFBP-3 were 0.91 (95% CI, 0.49–1.68), 0.47 (95% CI, 0.25–0.94), and 0.65 (95% CI, 0.35–1.20), respectively. The distribution of serum insulin levels in cases and controls were nearly identical. CONCLUSIONS The IGF-I level was not associated positively with the risk of prostate carcinoma; however, an increase in the IGFBP-3 level was associated with a modest decrease in risk. Cancer 2005. © 2004 American Cancer Society.

Objective: We examined breast cancer risk related to lifetime exposure to oral contraceptives (OCs) and hormone replacement therapy (HRT) in postmenopausal women. Methods: The Women's Contraceptive and Reproductive Experiences (CARE) Study was a population-based case–control study that included 1847 postmenopausal women with incident invasive breast cancer, and 1932 control subjects, identified using random digit dialing. Results: 45% of cases and 49% of controls used both OCs and HRT. OC users were not at increased risk regardless of subsequent HRT exposure. HRT users who had used OCs previously did not have a higher risk of breast cancer than women with no exposure to OCs. We observed a negative interaction (p-value: 0.032) of combined hormone replacement therapy (CHRT) and past OC use. The increase in risk with CHRT was stronger in women who had never used OCs in the past (odds ratio: 1.05; 95% confidence interval: 1.01–1.10 per year of exclusive CHRT use) than in women who had used OCs (odds ratio: 1.00; 95% confidence interval: 0.97–1.03). Conclusions: We found no indication that adverse effects of exposure to OCs or HRT appeared only in the presence of the other hormone or were exacerbated by exposure to the other hormone.

Hormone replacement therapy (HRT) has increased in the United States over the past 2 decades in response to reports of long-term health benefits. A relationship between HRT and breast cancer risk has been observed in a number of epidemiological studies. In 2002, the Women's Health Initiative Randomized Controlled Trial reported an association between continuous combined HRT and breast cancer risk. The objective of this study was to examine the association between breast cancer risk and HRT according to regimen and duration and recency of use.A multicenter, population-based, case-control study was conducted in five United States metropolitan areas from 1994 to 1998. Analyzed were data from 3823 postmenopausal white and black women (1870 cases and 1953 controls) aged 35-64 years. Odds ratios (ORs) were calculated as estimates of breast cancer risk using standard, unconditional, multivariable logistic regression analysis. Potential confounders were included in the final model if they altered ORs by 10% or more. Two-sided P values for trend were computed from the likelihood ratio statistic. Continuous combined HRT was associated with increased breast cancer risk among current users of 5 or more years (1.54; 95% confidence interval 1.10, 2.17). Additionally, a statistically significant trend indicating increasing breast cancer risk with longer duration of continuous combined HRT was observed among current users (P =.01). There were no positive associations between breast cancer risk and other HRT regimens. Our data suggest a positive association between continuous combined HRT and breast cancer risk among current, longer term users. Progestin administered in an uninterrupted regimen may be a contributing factor. Risk dissipates once use is discontinued.

Purpose: Racial differences in the incidence of squamous cell carcinoma of the bladder may provide insight into the pathogenesis of this disease. We determined the incidence of squamous cell carcinoma of the bladder according to race in the United States.Materials and Methods: Data obtained from the Surveillance, Epidemiology and End Results program from 1973 to 1997 were analyzed to determine the incidence of squamous cell carcinoma of the bladder in individuals 35 to 84 years old. Incidence rates by race and gender were then adjusted to the age distribution of the 1970 American population.Results: The average annual incidence of squamous cell carcinoma of the bladder was 1.20/100,000 in black and 0.60/100,000 in white Americans (relative risk 2.0, 95% CI 1.74 to 2.29). Black men were at increased risk compared with white men and black women were at increased risk compared with white women. The higher incidence in black versus white individuals existed in all age groups beyond 45 years and was pr...

Objective: Exercise has been hypothesized to influence cancer risk through a variety of mechanisms including hormonal, metabolic and immunologic effects, yet its relation with the risk of thyroid cancer has not been examined. We conducted a population-based case–control study in women aged 18–64 in three counties of western Washington State to assess the relation of recreational physical activity with risk of papillary thyroid cancer. Methods: Of 558 women with thyroid cancer of the follicular epithelium diagnosed during 1988–1994 who were identified as eligible, 468 (83.9%) were interviewed; this analysis was restricted to women with papillary histology (n = 410). Controls (n = 574) were identified by random digit dialing, with a response proportion of 73.6%. Logistic regression was used to calculate odds ratios (OR) and associated confidence intervals (CI) estimating the relative risk of papillary thyroid cancer associated with various aspects of recreational exercise. Results: Risk of thyroid cancer was reduced among women who reported that they engaged in regular recreational exercise during the 2 years before diagnosis relative to women who did not report exercise during that time period (OR = 0.76, 95% CI 0.59–0.98). A similar risk reduction was noted among women who reported having exercised regularly between ages 12 and 21 (OR = 0.83, 95% CI 0.64–1.1). However, no clear associations with aspects of recreational activity, including average hours exercised per week or weekly energy expenditure, were observed. Conclusions: These results provide some initial support for the hypothesis that physical activity may reduce risk of thyroid cancer.

OBJECTIVE: Postmenopausal women who receive sequential hormone replacement therapy with estrogen combined with progestogen for 10 to 24 d/mo for a prolonged period may have an elevated endometrial cancer risk relative to those who have never received hormone replacement therapy. We investigated whether daily use of estrogen and progestogen (continuous combined hormone replacement therapy) could diminish any excess endometrial cancer risk. STUDY DESIGN: A population-based study in Washington State obtained interview data from 969 women aged 45 to 74 years with endometrial cancer diagnosed during 1985 through 1991 or 1994 through 1995 and from 1325 age-matched control subjects selected primarily by random digit dialing. Women who had received only continuous combined hormone replacement therapy were compared with women who had only received another hormone replacement therapy regimen or who had never received hormone replacement therapy. RESULTS: The risk of endometrial cancer among users of continuous combined hormone replacement therapy (n = 9 case patients, n = 33 control subjects) relative to women who had never received hormone replacement therapy was 0.6 (95% confidence interval, 0.3-1.3); the risk relative to women who received hormone replacement that included progestogen for 10 to 24 d/mo was 0.4 (95% confidence interval, 0.2-1.1). Most continuous combined hormone replacement therapy use was short-term (

Background:Breast and thyroid cancer have been observed to occur more frequently than expected as multiple primary tumors in women. The study presented herein focuses on the effects of age at diagnosis and treatment for the first cancer on the development of the second cancer. Methods:This retrospective cohort study used a study population consisting of 38,632 women diagnosed with primary invasive breast cancer and 2189 women diagnosed with primary invasive thyroid cancer between 1974 and 1994. Cases were identified from records of the Cancer Surveillance System of western Washington and followed for subsequent cancer development through 1995. Results:Seventy-one women were diagnosed during their lives with both breast and thyroid cancers. Including cancers diagnosed during the same month as or after the initial cancer, the relative risk (RR) of breast cancer among women with thyroid cancer was 1.5 (95% confidence interval [CI] 1.1–2.0), and the RR of thyroid cancer among women with breast cancer was 1.5 (95% CI 1.1–2.2). Among women with thyroid cancer, risk of breast cancer was greatest when the latter cancer was diagnosed under 45 years of age (RR = 2.3, 95% CI 1.1–4.4). First course of treatment, including radiation or hormonal therapy to treat thyroid cancer, and radiation, chemotherapy, or hormonal therapy to treat breast cancer, did not alter a woman's risk of developing the second cancer. Conclusions:The data suggest that the incidence of breast and thyroid cancer may be related, and that in particular women with thyroid cancer may be at a moderately increased risk of developing breast cancer before age 45.

We analyzed data from a population-based case-control study of endometrial cancer. Our goal was to identify a subgroup of women in whom the additional cancer risk associated with unopposed estrogen use was sufficiently small so as to not be a deterrent to taking a hormone preparation of this type. Researchers interviewed women with endometrial cancer (N = 553) and controls (N = 752) regarding hormone use. The additional risk of endometrial cancer associated with unopposed estrogen use did not vary substantially in the presence or absence of hypertension, parity, oral contraceptive use, or smoking. The results suggest that, although heavier women may experience a greater risk of endometrial cancer associated with unopposed estrogen use (8.2 per 1,000 per year) than lighter women (4.2 per 1,000 per year), long-term users in the latter group nonetheless face a substantial absolute increase in risk. We conclude that subdividing women on the basis of the presence or absence of other known risk factors for endometrial cancer fails to delineate a subgroup that is exempt from the increased risk of this cancer associated with use of unopposed estrogens. 83.6% of estrogen users reported taking conjugated estrogens. (Epidemiology 1999;10:733–738)

Objectives: The reported mutagenic and carcinogenic effects of some chemicals present in hair dyes have raised concern that hair dye use could increase breast cancer risk. This case–control study evaluated how detailed aspects of hair coloring and hair spray application by reproductive-age women may affect breast cancer risk. Methods: Cases were white female residents of three counties of western Washington state 45 years of age or less, who were diagnosed with breast cancer between 1983 and 1990 (n = 844). A sample of similarly aged women residing in the same counties served as controls (n = 960). Information on hair coloring and hair spray use, as well as other exposures, was ascertained during in-person interviews. Results: Breast cancer cases were slightly more likely than controls to report ever having used some type of hair coloring application, including use of rinses, semi-permanent or permanent dyes, as well as bleaching then dyeing or frosting their hair (relative risk [RR] = 1.3, 95% CI = 1.0–1.6, adjusted for age, fullterm pregnancies, family history of breast cancer, and weight). In subgroup analyses, women with exclusive use of just one of these methods of hair coloring application had no elevation in risk (similarly adjusted RR = 1.1, 95% CI = 0.9–1.3), whereas women who used two or more of these methods did have an elevated risk (RR = 1.9, 95% CI = 1.4–2.5). Hair spray use was not related to the risk of breast cancer (ever versus never users: RR = 1.0, 95% CI = 0.8–1.3). Conclusion: The lack of an association between exclusive use of a single type of hair coloring application and breast cancer risk argues that hair coloring application does not influence breast cancer risk among reproductive-age women. Thus, the results of the present study, as well as negative ones from most (but not all) prior studies, are most consistent with the conclusion that neither hair coloring application nor hair spray application influences breast cancer risk.

Objective: To examine demographic and behavioral factors related to perineal application of powders. Methods: Controls from three case-control studies ( N = 1206) were asked identical questions about the use of genital powders by direct perineal application. The relationship of perineal powder application with demographic factors, reproductive factors, body mass index (BMI), douching, and alcohol and tobacco use was assessed. Data were analyzed by multiple logistic regression. Results: Women who douched (prevalence odds ratio [prevalence OR] 2.0, 95% confidence interval [CI] 1.0, 3.9), drank alcohol (prevalence OR 1.8, 95% CI 1.2, 2.8), smoked cigarettes (prevalence OR 1.3, 95% CI 1.0, 1.8), or were in the highest BMI quartile were more likely to engage in perineal use of powder (prevalence OR 1.6, 95% CI 1.1, 2.6). There appeared to be a close response relationship between the number of perineal applications of powder and BMI ( P Conclusion: Body mass index might confound the relationship between perineal powder application and the development of ovarian cancer. Other factors, such as alcohol and tobacco use and douching, are related to perineal use of powder and may represent similar behavioral characteristics.

Objective To determine whether a low dosage (0.3 mg/day) of unopposed conjugated estrogens can be used without incurring an elevated risk of endometrial cancer. Methods In this case-control study, cases ( n = 484) consisted of women diagnosed with endometrial cancer between 1985 and 1991 in three counties in Western Washington. Controls ( n = 780) were identified using random digit dialing within the same three counties. Subjects were interviewed in person to obtain basic demographic and medical history information, as well as specific information about hormone use. Result Eighteen cases and eight controls had taken 0.3 mg/day of unopposed conjugated estrogens and no other dose or preparation of estrogens (risk relative to that of women who had not taken postmenopausal hormones = 5.4, 95% confidence interval [CI] 2.3,13.0). The risk was particularly high in women whose use of this dose was both current and of more than 8 years' duration (odds ratio = 9.2, 95% CI 2.9, 29.0). The elevation in risk in users of 0.3 mg/day was similar in size to that associated with the daily unopposed use of 0.625 mg of conjugated estrogens. Conclusion The Result suggest that a dosage of 0.3 mg per day of unopposed conjugated estrogens is associated with an increased risk of endometrial cancer.

Objectives: Greater incidence of thyroid cancer in women than men, particularly evident during the reproductive years, has led to the suggestion that female hormones may increase risk of this disease. We conducted a population-based case-control study in women aged 18 to 64 years in three counties of western Washington State (United States) to assess the relation of use of exogenous hormones, including oral contraceptives (OC) and hormone replacement therapy (HRT), to risk of papillary thyroid cancer.

Summary Background Postmenopausal oestrogen therapy reduces the risk of osteoporosis and cardiovascular diseases but is associated with an increased risk of endometrial cancer. We have assessed the impact of a regimen of oestrogen with cyclic progestagen on risk of endometrial cancer for postmenopausal women. Methods We did a population-based case-control study of women aged 45–74 years in western Washington State, USA Cases were identified from a regional cancer registry as having histologically confirmed endometrial cancer during 1985–91. 832 (72%) of 1154 eligible cases completed interviews. Controls were identified by random digit dialling, screened for intact uterus, frequency matched for age and county, and randomly assigned a reference date within 1985–91. Interviews with 1114 (73%) of 1526 eligible controls were done. The women provided information about use of hormone replacement therapy, and reproductive and medical history before diagnosis date (cases) orreference date (controls). Findings Relative to women who had never used hormones (for >6 months), women who had taken unopposed oestrogen had a four-fold increase (95% CI 3·1–5·1) in risk of endometrial cancer. Women who used a combined therapy of oestrogen with cyclic progestagen (eg, medroxyprogesterone acetate) had a relative risk of 1·4 (1·0–1·9). Among women with fewer than 10 days of added progestagen per month, the relative risk was 3·1 (1·7–5·7), whereas that for women with 10–21 days of added progestagen was 1·3 (0·8–2·2). The use of these combined regimens for 5 or more years was associated with risks of 3·7 (1·7–8·2) and 2·5 (1·1–5·5), respectively, relative to non-users of hormones. Interpretation Postmenopausal women who use combined therapy of oestrogen with cyclic progestagen on a long-term basis have an increased risk of endometrial cancer compared with those who are not on hormone replacement, even when progestagen is added for 10 or more days per month. This increase is much smaller than that associated with unopposed oestrogen, but needs to be confirmed.

Data from a population-based case-control study were used to evaluate the risk of endometrial cancer among women who have used an intra-uterine device (IUD). Incident cases were identified between 1985 and 1991 among women aged 45-74 years who were residents of one of 3 counties in Washington State. Controls were selected by random digit dialing, and both groups of subjects received an in-person detailed interview. In this study population, women who had ever used an IUD were estimated to have a risk of endometrial cancer that was 0.61 times that of other women (95% CI 0.41-0.89). The reduction in cancer risk was not found to be dependent on duration of IUD use. There was a suggestion that women who had used intra-uterine contraception relatively late in reproductive life experienced a greater reduction in risk than those whose use was more distant or at a younger age. The relative risk among the small number of women who were currently using an IUD was 0.49 (95% CI 0.12-2.80). These results apply to the use of inert and copper IUDs as there was no use of progestin-releasing IUDs among women in the study population. The data from this and several other studies of the question support the hypothesis that use of an IUD has a favorable effect on the subsequent risk of endometrial cancer. The reason(s) for such a reduced risk is unclear.

Premature rupture of the amniotic membranes (PROM) occurs in up to 20% of all births. Although many studies have examined risk factors for PROM and, in particular, preterm PROM (PPROM, if less than 37 weeks' gestation), the aetiology of PROM recurrence has not been examined as closely. This study investigated factors that may increase the risk of PROM among women who have already experienced one PROM birth. Maternally linked Washington State birth certificates from 1984 to 1993 identified 208 women with consecutive PROM births. Controls were a random sample (n = 848) of women who had one birth on record complicated by PROM, but whose subsequent birth was not. Among women with a prior term PROM, increased risk for PROM recurrence (term PROM or PPROM) was associated with an intervening fetal death at less than 20 weeks' gestation (OR = 2.4, 1.3-4.5) and with parity of two or more (OR = 2.0, 1.3-3.4). None of the factors assessed significantly increased the risk of recurrence of PROM (term PROM or PPROM) among women with a prior PPROM. Other potential risk factors for PROM recurrence were evaluated within the two PROM groups (PPROM or term PROM at first birth) by stratifying among the cases according to gestational length at subsequent birth.

BACKGROUND This study investigates whether a positive family history of breast carcinoma is associated with improved survival after invasive breast carcinoma among women ages 21 through 45. METHODS Subjects were 733 nonadopted women born after 1944 who were diagnosed with primary invasive breast carcinoma between January 1983 and April 1990 while residing in the metropolitan Seattle area and who provided information on family history of breast carcinoma. Information on clinical characteristics and survival was obtained from a population-based cancer registry. Subjects were followed for survival through 1994. Cox proportional hazards models were used to estimate the relative risk (RR) of dying in relation to family history of breast carcinoma, adjusting for selected clinical characteristics, age and year of diagnosis, and prior mammograms. RESULTS The risk of dying among women with a first-degree family history of breast carcinoma was half that of women with no family history of breast carcinoma (RR = 0.5; 95% confidence interval [CI], 0.3–0.9). There was no evidence of a reduction in the risk of dying among women with only a second-degree family history of breast carcinoma (RR = 1; 95% CI, 0.6–1.4). These associations were adjusted for age and year of diagnosis, stage of disease, tumor size, bilaterality, and mammogram history. These findings were not further influenced by adjustment for initial treatment or the numbers and ages of relatives at risk for breast carcinoma. CONCLUSIONS Compared with women with neither a first- nor second-degree family history of breast carcinoma, the authors found that women who had a first-degree family history experienced increased survival. This finding did not appear to be attributable to differences in screening or treatment. To the extent that this difference is attributable to underlying biologic mechanisms, new insights into the natural history and treatment of breast carcinoma could result. Future studies should investigate whether specific susceptibility genes are associated with differential survival from breast carcinoma. Cancer 1996;78:1417-25.

Some researchers have hypothesized that omega-3 fatty acids, found primarily in fish oils, may protect against the development of rheumatoid arthritis. We conducted a population-based case-control study in women, comparing 324 incident rheumatoid arthritis cases with 1,245 controls. We used a food frequency questionnaire to ascertain diet during a 1-year period 5 years before a reference date (first physician visit for joint-symptoms). Consumption of broiled or baked fish, but not of other types of fish, was associated with a decreased risk of rheumatoid arthritis. The adjusted odds ratios (OR) for 1-2 servings andor = 2 servings of broiled or baked fish per week, compared with1 serving, were 0.78 [95% confidence interval (CI) = 0.53-1.14] and 0.57 (95% CI = 0.35-0.93). Other analyses showed associations with protein as a percentage of calories (adjusted OR for the top quartile as compared with the bottom quartile = 0.65; 95% CI = 0.46-0.94) and total calories (adjusted OR for the top quartile = 1.62; 95% CI = 1.15-2.28). The associations with broiled or baked fish, protein, and calories became stronger when we restricted our analysis to cases positive for rheumatoid factor. These results support the hypothesis that omega-3 fatty acids may help prevent rheumatoid arthritis.

The authors analyzed data from a population-based case-control study of breast cancer in middle-aged women residing in King County, Washington, to examine the relation between occupation and breast cancer risk. A total of 537 cases and 492 controls completed in-person interviews. Subjects provided job titles and years of employment for their three main occupations since age 18. While there were case-control differences in the frequency with which certain jobs were reported, all were within the limits of chance, given no true association. Also, few additional increases in risk were associated with long-term employment. Relative risk (RR) estimates were elevated for women working in precision textile and apparel jobs (six cases and one control, RR = 5.2). To a lesser extent, RR estimates were also elevated for receptionists, cosmetologists, and the category of painters/sculptors/printmakers. A slight increase in risk was associated with several occupations, including nursing and teaching.

Certain events of reproductive life, especially completed pregnancies, have been found to influence a woman's risk of breast cancer. Prior studies of the relationship between breast cancer and a history of incomplete pregnancies have provided inconsistent results. Most of these studies included women beyond the early part of their reproductive years at the time induced abortion became legal in the United States.We conducted a case-control study of breast cancer in young women born recently enough so that some or most of their reproductive years were after the legalization of induced abortion to determine if certain aspects of a woman's experience with abortion might be associated with risk of breast cancer.Female residents of three counties in western Washington State, who were diagnosed with breast cancer (n = 845) from January 1983 through April 1990, and who were born after 1944, were interviewed in detail about their reproductive histories, including the occurrence of induced abortion. Case patients were obtained through our population-based tumor registry (part of the Surveillance, Epidemiology, and End Results Program of the National Cancer Institute). Similar information was obtained from 961 control women identified through random digit dialing within these same counties. Logistic regression analysis was used to estimate odds ratios and confidence intervals (CIs).Among women who had been pregnant at least once, the risk of breast cancer in those who had experienced an induced abortion was 50% higher than among other women (95% CI = 1.2-1.9). While this increased risk did not vary by the number of induced abortions or by the history of a completed pregnancy, it did vary according to the age at which the abortion occurred and the duration of that pregnancy. Highest risks were observed when the abortion was done at ages younger than 18 years--particularly if it took place after 8 weeks' gestation--or at 30 years of age or older. No increased risk of breast cancer was associated with a spontaneous abortion (RR = 0.9; 95% CI = 0.7-1.2).Our data support the hypothesis that an induced abortion can adversely influence a woman's subsequent risk of breast cancer. However, the results across all epidemiologic studies of this premise are inconsistent--both overall and within specific subgroups. The risk of breast cancer should be reexamined in future studies of women who have had legal abortion available to them throughout the majority of their reproductive years, with particular attention to the potential influence of induced abortion early in life.Epidemiologists compared data on 845 white women who were diagnosed with breast cancer between January 1983 and April 1990, were born after 1944, and lived in King, Pierce, or Snohomish counties in Washington State with data on 961 white women with no breast cancer from the same counties. They wanted to determine whether induced abortion increases the risk of breast cancer. Restricting cases to women born after 1944 allowed the researchers to focus only on legal induced abortions. When the researchers limited the analysis only to women who had been pregnant at least once, the risk of developing breast cancer in women who had had at least 1 induced abortion was 50% greater than those who had not had an induced abortion. This risk differed depending on the age at which the women underwent the induced abortion and the duration of that pregnancy. A gestational age (at the time of the first aborted pregnancy) of 9-12 weeks carried the highest risk of breast cancer (RR = 1.9 vs. 1.4 for =or 8 weeks and =or 13 weeks). Further, the breast cancer risk was greatest among women who underwent the induced abortion when they were less than 18 years old (relative risk [RR] = 2.5). It was especially high for women who were less than 18 years old and who had the abortion between 9 and 24 weeks of gestation (RR = 9). It was also high for those who were at least 30 years old at the time of the abortion (RR = 2.1). Spontaneous abortion was not associated with an increased risk (RR = 0.9). Neither the number of induced abortions nor the history of a completed pregnancy were associated with an increased risk of breast cancer. These findings suggest that an induced abortion during the last month of the first trimester increases the risk of breast cancer and that women who were at a very young age at the time of the first induced abortion face an increased risk of breast cancer.

Epidemiologic studies are consistent in finding that women who have had at least one birth are less likely to develop endometrial cancer. Less clear is whether timing of pregnancies during reproductive life influences risk, and the degree to which incomplete pregnancies are associated with a reduced risk.We evaluated pregnancy history in relation to endometrial cancer risk using data from a series of 4 population-based endometrial cancer case-control studies of women 45-74 years of age (1712 cases and 2134 controls) during 1985-2005 in western Washington State. Pregnancy history and information on other potential risk factors were collected by in-person interviews.Older age at first birth was associated with a reduced risk of endometrial cancer after adjustment for number of births and age at last birth (test for trend P = 0.004). The odds ratio comparing women at least 35 years of age at their first birth with those younger than 20 years was 0.34 (95% confidence interval = 0.14-0.84). Age at last birth was not associated with risk after adjustment for number of births and age at first birth (test for trend P = 0.830). Overall, a history of incomplete pregnancies was not associated with endometrial cancer risk to any appreciable degree.In this study, older age at first birth was more strongly associated with endometrial cancer risk than was older age at last birth. To date, there remains some uncertainty in the literature on this issue.

To determine whether pelvic damage is associated with positive Chlamydia trachomatis serology in women with tubal ectopic pregnancy.Cross-sectional retrospective study.A prepaid health maintenance organization.Two-hundred eighty-one women admitted with confirmed tubal ectopic pregnancy were interviewed for history of sexually transmitted diseases. Chlamydia serology was obtained for 135 subjects, and operative findings were available for 121 of these.None.Pelvic damage, as determined by review of operative findings of the pelvis at the time of ectopic surgery.Pelvic damage was associated with positive chlamydia serology with an adjusted odds ratio of 4.2 (95% confidence interval: 1.8 to 9.7). Moderate and severe pelvic damage were more strongly associated with positive serology than mild damage.Women with ectopic pregnancies and antibodies to C. trachomatis are more likely to have damaged pelves than women with ectopic pregnancies without such antibodies. Prevention or early treatment of C. trachomatis infection may reduce pelvic damage and, therefore, reduce incidence of ectopic pregnancy.

Using data from a population-based, case-control study, we assessed risk of tubal pregnancy associated with use of an intrauterine device (IUD) at the time of conception. Cases were 249 members of Group Health Cooperative of Puget Sound who experienced a tubal pregnancy between 1981 and 1986. Controls were 831 members at risk of ectopic pregnancy who were similar to cases with respect to age and county of residence, but otherwise selected at random. Risk of tubal pregnancy associated with current IUD use was compared separately to that among users of various other (or no) contraceptive methods. Tubal pregnancy was more likely to occur among IUD users than among women using oral contraceptives [relative risk (RR) = 3.8, 95% confidence interval (CI) = 1.5-9.9] or barrier methods (RR = 3.6, 95% CI = 1.6-8.1), or, to a lesser extent, among women who had been surgically sterilized (RR = 1.6, 95% CI = 0.8-3.5). In contrast, IUD users were much less likely to experience a tubal pregnancy (RR = 0.2, 95% CI = 0.1-0.4) than were women who were currently not contracepting. For most women, the decision to use an IUD occurs within the context of choosing among various contraceptive methods. Our results indicate that, for these women, the decision to use an IUD results in increased risk of ectopic pregnancy while the device is in use.In King County, Washington, health workers interviewed 249 members of Group Health Cooperative of Puget Sound who had had an ectopic pregnancy between October 1981 and September 1986 and 831 randomly selected, age- and county-matched controls who were at risk of ectopic pregnancy. Researchers wanted to examine the risk of ectopic pregnancy associated with IUD use at time of conception. The Copper 7 IUD was the most common IUD used (66.7% of cases and 65% of controls). Cases were more likely to have a positive titer for C. trachomatis than controls (33.8% vs. 17.6%). In comparison with users of oral contraceptives, barrier methods, and tubal sterilization, IUD use increased the risk of ectopic pregnancy (relative risk [RR] = 3.8, 3.6, and 1.6, respectively). On other hand, IUD users were less likely to experience ectopic pregnancy than women not using any contraception or using other contraceptive methods (RR = 0.2 and 0.6, respectively). All the aforementioned results did not change when the researchers only considered women using the Copper 7 IUD. The risk of ectopic pregnancy fell with increasing duration of IUD use among current users, but the numbers of women were small (e.g., odds ratio for 36-72 months = 0.6 and for 72 months = 0.4). These findings suggest that, for women in the midst of choosing a contraceptive, the risk of ectopic pregnancy is high when an IUD is in situ.

Objective. To examine fecundity prior to disease onset in women with rheumatoid arthritis (RA). Methods. Two hundred fifty-nine RA patients with an opportunity for pregnancy were compared with 1,258 control women as part of a prospective case-control study of recent-onset RA in women. Results. A 12-month or longer interval to pregnancy was found in 42% of RA cases compared with 34% of controls (odds ratio = 1.44, 95% confidence interval 1.10, 1.91). This difference was not accounted for by an older age when attempting to become pregnant among the RA cases compared with the controls. The result was unrelated to rheumatoid factor or HLA-DR4 status. Conclusion. Women with RA were found to have decreased fecundity prior to disease onset, compared with control women.

The usefulness of landline random digit dialing (RDD) in epidemiologic studies is threatened by the rapid increase in households with only cellular telephone service. This study assessed the feasibility of including cellular telephone numbers in RDD and differences between young adults with landline telephones and those with only cellular telephones. Between 2008 and 2009, a total of 9,023 cellular telephone numbers were called and 43.8% were successfully screened; 248 men and 249 women who resided in 3 Washington State counties, were 20-44 years of age, and used only cellular telephones were interviewed. They were compared with 332 men and 526 women with landline telephones interviewed as controls for 2 case-control studies conducted in parallel with cellular telephone interviewing. Cellular-only users were more likely to be college educated and less likely to have fathered/birthed a child than were their landline counterparts. Male cellular-only users were less likely to be obese and more likely to exercise, to be Hispanic, and to have lower incomes, while female cellular-only users were more likely to be single than landline respondents. Including cellular telephone numbers in RDD is feasible and should be incorporated into epidemiologic studies that rely on this method to ascertain subjects, although low screening rates could hamper the representativeness of such a sample.

Objective Previous studies have evaluated the correlation between rheumatoid arthritis (RA) risk and pregnancy history, with conflicting results. Fetal cells acquired during pregnancy provide a potential explanation for modulation of RA risk by pregnancy. The present study was undertaken to examine the effect of parity on RA risk. Methods We examined parity and RA risk using results from a population-based prospective study in Seattle, Washington and the surrounding area and compared women who were recently diagnosed as having RA (n = 310) with controls (n = 1,418). We also evaluated the distribution of parity in cases according to HLA genotype. Results We found a significant reduction of RA risk associated with parity (relative risk [RR] 0.61 [95% confidence interval 0.43–0.86], P = 0.005). RA risk reduction in parous women was strongest among those who were younger. Most striking was that RA risk reduction correlated with the time that had elapsed since the last time a woman had given birth. RA risk was lowest among women whose last birth occurred 1–5 years previously (RR 0.29), with risk reduction lessening progressively as the time since the last birth increased (for those 5–15 years since last birth, RR 0.51; for those >15 years, RR 0.76), compared with nulliparous women (P for trend = 0.007). No correlation was observed between RA risk and either age at the time a woman first gave birth or a woman's total number of births. Among cases with the highest genetic risk of RA (i.e., those with 2 copies of RA-associated HLA alleles), a significant underrepresentation of parous women versus nulliparous women was observed (P = 0.02). Conclusion In the present study, there was a significantly lower risk of RA in parous women that was strongly correlated with the time elapsed since a woman had last given birth. While the explanation for our findings is not known, HLA-disparate fetal microchimerism can persist many years after a birth and could confer temporary protection against RA.

This study examined the changes over time in the residential status of telephone numbers and the characteristics of households with telephone numbers that changed from nonresidential to residential. The authors determined the status in 1987 of all phone numbers (n = 9,107) that had been found to be nonresidential in six case-control studies conducted between 1979 and 1986 in Washington State. A telephone interview to obtain information on household characteristics was completed for 1,333 of the 1,901 phone numbers that had become residential by 1987. The interviews revealed that households with phone numbers that had previously been nonresidential differed from the general population with respect to household income, the age of household members, and the education of the head of the household. Data for the same area showed that the proportion of all phone numbers that were residential changed differentially according to the prefix (which roughly defines geographic area) during a 12-month period between 1987 and 1988, with some prefixes showing increases in residential phone numbers of more than 20%, while other prefixes decreased or stayed the same over the same period. We conclude that methods of random digit dialing that use two-stage designs or exclude previously dialed numbers may result in biased sampling unless changes over time are considered.

To determine whether maternal infertility treatment is associated with adverse outcomes.Population-based cohort study using linked birth certificate-hospital discharge data.Washington State.Live-born singleton infants conceived with infertility treatment between 2003 and 2006 (n = 2,182) and a random sample of live-born singleton infants conceived spontaneously, frequency matched by birth year (n = 10,989).None.Mantel-Haenszel adjusted relative risks (RRs) and 95% confidence intervals (CIs) were computed for low birth weight, delivery at37 weeks, small for gestational age infants, any malformation, placenta previa, and placenta abruptio.Women with infertility treatment were at increased risk of placental abnormalities, including placenta abruptio (RR, 1.6; 95% CI, 1.1-2.5) and placenta previa (RR, 3.0; 95% CI, 2.0-4.7). Their infants were more likely to be delivered at37 weeks (RR, 1.7; 95% CI, 1.4-1.9) or weigh2500 g (RR, 1.4; 95% CI, 1.1-1.7); however, they were not at increased risk of being small for gestational age. An increased risk of malformations was observed in infants born to older women with infertility treatment, but not to younger women.Women using infertility treatment are at increased risk for delivering preterm, placenta previa, and placenta abruptio. Studies with measurement of specific infertility treatments will help identify the mechanisms.

In a population-based study of ectopic pregnancy, a card-back system of initial subject contact yielded a positive response from 85.1% of potential cases and 65.0% of potential controls. We subsequently recontacted by telephone potential controls who had declined to participate and offered them $10 compensation for participation. We recontacted 205 of the 330 control women who had refused to participate. Twenty-eight were found to be ineligible, and 75.7% of the remaining 177 agreed to participate on recontact. The additional 125 women were not recontacted, 9 because of firm initial refusals and 116 because the study ended before contact could be sought or made. Controls who initially declined to participate but subsequently agreed differed from those who initially agreed on a number of demographic and reproductive characteristics, and estimates of ectopic pregnancy risk associated with induced abortion and tubal sterilization changed slightly with the inclusion of initial nonparticipants. We conclude that use of a card-back system of subject contact yields a low level of positive response among reproductive-aged women and that many initial nonparticipants can be converted into participants by personal contact and the offer of compensation.

Two hundred nine female enrollees of the Group Health Cooperative of Puget Sound who developed advanced-stage breast cancer during the period 1982-1988 were interviewed about their practice of breast self-examination (BSE), use of other breast cancer screening modalities, and medical and reproductive histories. Each subject's description of how she performed the examination was scored according to her mention of up to 10 recommended BSE techniques. A random sample of 433 women without advanced-stage breast cancer from the same population was interviewed for comparison. Relative to women not practicing BSE, the risk of advanced-stage breast cancer among BSE users was 1.15 (95% confidence interval, 0.73-1.81). Frequency of BSE did not differ between women with advanced-stage breast cancer and control subjects, whether in all subjects or in subgroups defined by age, use of mammography, or frequency of clinical breast examinations. While self-described proficiency in BSE was generally low in both case and control subjects, the small percentage of women reporting more thorough self-examinations, regardless of frequency, had about a 35% decrease in the occurrence of advanced-stage breast cancer compared to women who did not perform BSE. These results suggest that, while carefully performed BSE may avoid the development of some advanced-stage breast cancers, BSE as practiced by most Seattle-area women is of little or no benefit.

The authors sought to test the hypothesis that characteristics and exposures which influence the balance of estrogen and progesterone bear on the incidence of endometrial hyperplasia (EH), a noninvasive proliferation of the lining of the uterus. Cases included all female members of Group Health (Washington State) who were diagnosed with complex EH or EH with atypia during the period 1985-2003 and whose diagnoses were confirmed in a pathology review (n = 446). Controls were selected randomly from Group Health membership files and were matched to the cases by age and enrollment status at the reference date. An increased risk of EH was associated with increasing body mass index and nulliparity. There was a suggestion of a decreased risk of EH with atypia among current smokers. No association with diabetes or hypertension was found. The risk factors observed to be associated with EH in this study are similar to those associated with endometrial cancer. Whether these risk factors predispose women to cancer simply by increasing EH incidence or continue to augment cancer risk even after EH is present is currently unknown.

Combined estrogen and progestin hormone therapy (CHT) increases breast cancer risk, but this risk varies by breast cancer type. Several studies indicate that CHT is more strongly related to lobular carcinoma risk than to ductal carcinoma risk, but these studies have been limited in their assessments of recency and duration of use, and none included a centralized pathology review. We conducted a population-based case-control study consisting of 324 lobular, 196 ductal-lobular, and 524 ductal cases diagnosed from 2000 to 2004 and 469 controls ages 55 to 74 years old. Tissue specimens were centrally reviewed for 83% of cases. Associations between hormone use and breast cancer risk were evaluated using polytomous logistic regression. Current CHT users had 2.7-fold [95% confidence interval (95% CI), 1.7-4.2] and 3.3-fold (95% CI, 2.0-5.7) elevated risks of lobular and ductal-lobular carcinomas, respectively, regardless of tumor stage, size, or nodal status. Elevations in risk were observed only among users of CHT for ≥3 years. Among ductal-lobular cases, CHT increased risk of tumors that were ≥50% lobular (odds ratio, 4.8; 95% CI, 2.1-11.1) but not tumors that were

Random digit dialing is a method commonly used to select random population samples in epidemiologic research. Although random digit dialing is generally presumed to provide representative samples, coverage and nonresponse errors may affect the degree to which the sample is representative. The present investigation was undertaken to determine whether the geographic distributions of samples selected using variations of the basic random digit dialing technique accurately reflect the underlying population distribution, and if not, whether such samples tend to be either more or less dispersed than the populations from which they were selected. Data regarding control groups from three case-control studies conducted from 1983–1986 were utilized. The residence addresses of 998 controls were located and assigned an X-Y coordinate and census tract designation within a three-county geographic area in northwest Washington State. Initially, the spatial distributions of controls were examined graphically in relation to the age-sex structure of the underlying population. No differences in geographic pattern were apparent A more formal statistical evaluation was conducted based on centrographic techniques utilizing two measures to describe the spatial distribution of a set of points. Results indicate that the samples chosen were neither more nor less dispersed than the underlying populations. However, the geographic centers of samples selected using primary numbers tended to be shifted from the centers of their respective populations. Several possible explanations for such shifts are considered, and extensions of the analytical approach are suggested in relation to the further evaluation of population sampling and the investigation of space-time aggregations of disease.

To determine whether risk of endometrial cancer among women with type 2 diabetes differs with respect to other endometrial cancer risk factors, the authors used data from a population-based case-control study (1,303 cases and 1,779 controls) conducted in western Washington State during 1985-1999. History of type 2 diabetes was associated with endometrial cancer (odds ratio (OR) = 1.7, 95% confidence interval (CI): 1.2, 2.3), more strongly among women with a recent diabetes diagnosis (5 years) (OR = 2.6, CI: 1.5, 4.7) than among those with a more distant diagnosis (or =5 years) (OR = 1.3, CI: 0.8, 1.9). Type 2 diabetes was associated with endometrial cancer among women with a body mass index (BMI) (weight (kg)/height (m)(2)) less than 35 but not among women with a BMI of 35 or more. The observed associations persisted after finer adjustment for BMI to control for residual confounding. History of diabetes was associated with a twofold increased risk of endometrial cancer among hypertensive women, but no association was observed among nonhypertensive women. The risk associated with type 2 diabetes appeared not to vary greatly with respect to other endometrial cancer risk factors. These results support the hypothesis that type 2 diabetes is associated with endometrial cancer irrespective of the presence of other risk factors for this disease, except possibly hypertension and extreme obesity.

It is unknown whether postmenopausal unopposed estrogen users are better off, in terms of endometrial cancer risk, switching to a combined estrogen–progestin regimen or stopping hormone use altogether. We analyzed data from a series of three population-based case–control studies in western Washington state during 1985–1999, comparing proportions of “switchers” and “stoppers” in cases and controls. We also assessed whether the risk of endometrial cancer in either group of former unopposed estrogen users returned to that of never users. After multivariate adjustment using unconditional logistic regression, women who switched to a combined regimen with a progestin added for at least ten days/month (37 cases, 47 controls) had half the risk of endometrial cancer of women who stopped hormone use altogether (86 cases, 78 controls) (adjusted odds ratio = 0.5, 95% confidence interval: 0.3–1.1). Most subgroups of former users, whether they switched or stopped, had some increased risk of endometrial cancer compared to never users. Results from this study suggest that unopposed estrogen users may reduce their risk of endometrial cancer more by switching to a combined regimen with progestin added for at least ten days/month than by stopping hormone use altogether.

We conducted a nested case-control study within a cohort of elderly Americans to examine the role of the insulin-like growth factor (IGF) signaling pathway in prostate cancer etiology. The distribution of genotypes of IGF-I (CA)n, IGF binding protein-3 (IGFBP-3) A-202C, and of the 2-bp deletion and (AGG)n polymorphisms in IGF-I receptor (IGF-IR) was compared between men with prostate cancer (n = 213) and equal number of controls matched on year of blood draw, survival until the date of diagnosis, race, and age. Among controls, the number of CA repeats in IGF-I was not correlated to any appreciable degree with plasma IGF-I concentration, whereas the IGFBP-3 CC genotype was associated with a relatively low level of plasma IGFBP-3. There was no association between prostate cancer risk and the number of CA repeats in IGF-I, IGFBP-3 genotype, or the presence of the 2-bp deletion in IGF-IR. There was a small increased risk among men who did not carry two copies of the (AGG)7 allele of IGF-IR. These results add to the evidence that the number of IGF-I CA repeats is not associated with prostate cancer risk. Our observation that men who do not carry two copies of the IGF-IR (AGG)7 allele are at increased risk of prostate cancer merits further investigation. (Cancer Epidemiol Biomarkers Prev 2006;15(12):2461–6)

There is a wide range of aggressiveness of endometrial tumors, some being indolent and easily treated while others metastasize and prove fatal. The authors used data from three population-based, case-control studies to determine if etiologic factors differ for aggressive disease. Interview data were obtained from 1,304 female residents of western Washington State who were 45-74 years of age and diagnosed with endometrial cancer during 1985-1991, 1994-1995, and 1997-1999 and from 1,779 controls who were of similar ages and selected primarily by random digit dialing. As a means of gauging aggressiveness, tumor characteristics were abstracted from the population-based cancer registry that serves western Washington State. The risk of endometrial cancer among long-term users (> or = 8 years) of unopposed estrogens was particularly high for the least aggressive tumors (odds ratio = 18.6, 95% confidence interval: 12.2, 28.6) but was elevated for moderate and highly aggressive tumors as well (odds ratios = 6.6 and 7.1, respectively). Women who were obese, had a history of diabetes, and had fewer than two children were also at increased risk, regardless of tumor aggressiveness, while oral contraceptive users were at decreased risk of only relatively more aggressive disease. In general, a woman's risk of endometrial cancer appears to be influenced by similar risk factors regardless of disease severity.

Objective. —To determine the risk of breast cancer in relation to the use of combined estrogen and progestin hormone replacement therapy (HRT). Design. —A population-based case-control study. Setting. —The general female population of King County in western Washington State. Participants. —Middle-aged (50 to 64 years) women, including 537 patients with incident primary breast cancer diagnosed between January 1,1988, and June 30, 1990, who were ascertained through the Seattle—Puget Sound Surveillance, Epidemiology, and End Results cancer registry and 492 randomly selected control women without a history of breast cancer. Main Outcome Measure. —Breast cancer risk in relation to use of menopausal hormones. Results. —Menopausal hormones of some type had been used by 57.6% of breast cancer cases and 61.0% of comparison women. The women who had ever taken combined estrogen-progestin HRT, representing 21.5% of cases and 21.3% of controls, were not at increased risk of breast cancer (relative odds [RO]=0.9; 95% confidence interval [CI], 0.7 to 1.3). Compared with nonusers of menopausal hormones, those who used estrogen-progestin HRT for 8 or more years had, if anything, a reduced risk of breast cancer (RO=0.4; 95% CI, 0.2 to 1.0). Conclusions. —On the whole, the use of estrogen with progestin HRT does not appear to be associated with an increased risk of breast cancer in middle-aged women. Nonetheless, since the use of combined estrogen-progestin HRT has only recently become prevalent, future investigations must assess whether breast cancer incidence is altered many years after estrogen-progestin HRT has been initiated, particularly among long-term users. (JAMA. 1995;274:137-142)

This study was conducted to assess the histopathological features of breast cancers in women diagnosed with breast cancer at 50-64 years of age who have and have not used hormone replacement therapy (HRT). A case-case analysis of the tumors from women aged 50-64 years who participated in a multicenter population-based case-control study of invasive breast cancer was conducted. In-person interviews collected a detailed history of all episodes of hormone use. Information was collected on selected tumor characteristics from 2346 women with breast cancer. Polytomous logistic regression was used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs), contrasting the histopathological characteristics of the tumors of women who used various regimens of HRT with those of women who have never used HRT. The tumors of cases who used each regimen of HRT were smaller and of earlier stage than those of non-HRT users. Adjustment for screening diminished the magnitude of the effect, and only cases who used estrogen alone (estrogen replacement therapy) had reduced odds of being diagnosed with later-stage disease (regional or distant) than cases who never used HRT (OR, 0.7; 95% CI, 0.6-0.9). Higher proportions of estrogen receptor (ER)- and progesterone receptor (PR)-positive tumors were seen in cases who used any regimen of HRT versus those who did not use HRT. However, after adjustment for age and race, only the tumors of cases who used continuous combined HRT remained more likely to be ER+ and PR+ [OR ER- = 0.6 (95% CI, 0.4-0.9) and OR PR- = 0.5 (95% CI, 0.4-0.7)]. The tumors of women with breast cancer who used HRT have some better prognostic factors than those of women who have not used HRT. However, with the exception of the results noted above, this advantage may be due to the racial and age differences in those who use the various regimens of HRT and the effect of more frequent screening among HRT users, leading to earlier diagnosis.