Quantitative measures of estrogen receptor expression in relation to breast cancer-specific mortality risk among white women and black women.

INTRODUCTION: The association of breast cancer patients' mortality with estrogen receptor (ER) status (ER + versus ER-) has been well studied. However, little attention has been paid to the relationship between the quantitative measures of ER expression and mortality. METHODS: We evaluated the association between semi-quantitative, immunohistochemical staining of ER in formalin-fixed paraffin-embedded breast carcinomas and breast cancer-specific mortality risk in an observational cohort of invasive breast cancer in 681 white women and 523 black women ages 35-64 years at first diagnosis of invasive breast cancer, who were followed for a median of 10 years. The quantitative measures of ER examined here included the percentage of tumor cell nuclei positively stained for ER, ER Histo (H)-score, and a score based on an adaptation of an equation presented by Cuzick and colleagues, which combines weighted values of ER H-score, percentage of tumor cell nuclei positively stained for the progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) results. This is referred to as the ER/PR/HER2 score. RESULTS: After controlling for age at diagnosis, race, study site, tumor stage, and histologic grade in multivariable Cox proportional hazards regression models, both percentage of tumor cell nuclei positively stained for ER (Ptrend = 0.0003) and the ER H-score (Ptrend = 0.0004) were inversely associated with breast cancer-specific mortality risk. The ER/PR/HER2 score was positively associated with breast cancer-specific mortality risk in women with ER + tumor (Ptrend = 0.001). Analyses by race revealed that ER positivity was associated with reduced risk of breast cancer-specific mortality in white women and black women. The two quantitative measures for ER alone provided additional discrimination in breast cancer-specific mortality risk only among white women with ER + tumors (both Ptrend ≤ 0.01) while the ER/PR/HER2 score provided additional discrimination for both white women (Ptrend = 0.01) and black women (Ptrend = 0.03) with ER + tumors. CONCLUSIONS: Our data support quantitative immunohistochemical measures of ER, especially the ER/PR/HER2 score, as a more precise predictor for breast cancer-specific mortality risk than a simple determination of ER positivity.

Mortality risk of black women and white women with invasive breast cancer by hormone receptors, HER2, and p53 status.

BACKGROUND: Black women are more likely than white women to have an aggressive subtype of breast cancer that is associated with higher mortality and this may contribute to the observed black-white difference in mortality. However, few studies have investigated the black-white disparity in mortality risk stratified by breast cancer subtype, defined by estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) status. Furthermore, it is not known whether additional consideration of p53 protein status influences black-white differences in mortality risk observed when considering subtypes defined by ER, PR and HER2 status. METHODS: Four biomarkers were assessed by immunohistochemistry in paraffin-embedded breast tumor tissue from 1,204 (523 black, 681 white) women with invasive breast cancer, aged 35-64 years at diagnosis, who accrued a median of 10 years' follow-up. Multivariable Cox proportional hazards regression models were fit to assess subtype-specific black-white differences in mortality risk. RESULTS: No black-white differences in mortality risk were observed for women with triple negative (ER-negative [ER-], PR-, and HER2-) subtype. However, older (50-64 years) black women had greater overall mortality risk than older white women if they had been diagnosed with luminal A (ER-positive [ER+] or PR+ plus HER2-) breast cancer (all-cause hazard ratio, HR, 1.88; 95% confidence interval, CI, 1.18 to 2.99; breast cancer-specific HR, 1.51; 95% CI, 0.83 to 2.74). This black-white difference among older women was further confined to those with luminal A/p53- tumors (all-cause HR, 2.22; 95% CI, 1.30 to 3.79; breast cancer-specific HR, 1.89; 95% CI, 0.93 to 3.86). Tests for homogeneity of race-specific HRs comparing luminal A to triple negative subtype and luminal A/p53- to luminal A/p53+ subtype did not achieve statistical significance, although statistical power was limited. CONCLUSIONS: Our findings suggest that the subtype-specific black-white difference in mortality risk occurs mainly among older women diagnosed with luminal A/p53- breast cancer, which is most likely treatable. These results further suggest that factors other than subtype may be relatively more important in explaining the increased mortality risk seen in older black women.

Estrogen-related genes and their contribution to racial differences in breast cancer risk.

Racial differences in breast cancer risk, including the risks of hormone receptor subtypes of breast cancer, have been previously reported. We evaluated whether variation in genes related to estrogen metabolism (COMT, CYP1A1, CYP1B1, CYP17A1, CYP19A1, ESR1, GSTM1, GSTP1, GSTT1, HSD17B1, SULT1A1, and UGT1A1) contributes to breast cancer risk and/or racial differences in risk within the CARE study, a multi-centered, population-based case-control study of breast cancer. Genetic variation was assessed as single nucleotide polymorphisms (SNPs), haplotypes, and SNP-hormone therapy (HT) interactions within a subset of 1,644 cases and 1,451 controls, including 949 Black women (493 cases and 456 controls), sampled from the CARE study population. No appreciable associations with breast cancer risk were detected for single SNPs or haplotypes in women overall. We detected SNP-HT interactions in women overall within CYP1B1 (rs1800440; p (het) = 0.003) and within CYP17A1 (rs743572; p (het) = 0.009) in which never users of HT were at a decreased risk of breast cancer, while ever users were at a non-significant increased risk. When investigated among racial groups, we detected evidence of an SNP-HT interaction with CYP1B1 in White women (p value = 0.02) and with CYP17A1 in Black women (p value = 0.04). This analysis suggests that HT use may modify the effect of variation in estrogen-related genes on breast cancer risk, which may affect Black and White women to a different extent.

Breast cancer risk and ovariectomy, hysterectomy, and tubal sterilization in the women's contraceptive and reproductive experiences study.

Removal or impairment of ovaries before menopause may affect a woman's breast cancer risk by altering her cumulative exposure to ovarian hormones. The Women's Contraceptive and Reproductive Experiences Study, a population-based, multicenter case-control study of incident invasive breast cancer, recruited women aged 35-64 years (4,490 cases and 4,611 controls) who provided data on ovariectomy, hysterectomy, and tubal sterilization during in-person interviews. Controls were frequency-matched to cases by age, race, and study site. Unconditional logistic regression analysis was used. Women who had not undergone premenopausal reproductive surgery were the referent group. Bilateral ovariectomy was associated with reduced breast cancer risk overall (odds ratio (OR) = 0.59, 95% confidence interval (CI): 0.50, 0.69) and among women <45 years of age (ORs ranged from 0.31 to 0.52), but not among those who were older at surgery. It was also associated with a reduced risk for estrogen and progesterone receptor-positive tumors (OR = 0.63, 95% CI: 0.52, 0.75) but not receptor-negative tumors. Hysterectomy with ovarian conservation (OR = 0.83, 95% CI: 0.72, 0.96) and hysterectomy with partial ovary removal (OR = 0.73, 95% CI: 0.59, 0.91) were also associated with lower risk. No association with breast cancer risk was observed with tubal sterilization only or partial ovariectomy without hysterectomy. Reproductive organ surgeries may alter ovarian hormone levels, thereby affecting breast cancer risk.

Does antidepressant use attenuate the risk of a major depressive episode in pregnancy?

BACKGROUND: Many women become pregnant while undergoing antidepressant treatment and are concerned about continuing antidepressant medication. However, antidepressant discontinuation may increase the risk of a new episode of major depressive disorder. We sought to estimate differences in the risk of developing a new major depressive episode among pregnant and postpartum women with recurrent illness who either did or did not use antidepressants. METHODS: Participants were recruited from obstetrical settings; we analyzed a subgroup of 778 women with a history of a depressive disorder. Diagnoses were determined by the Composite International Diagnostic Interview administered twice in pregnancy and once after delivery. We used Cox Regression to model onset of a major depressive episode with a time-dependent predictor of antidepressant use. RESULTS: There was no clear difference in risk of a major depressive episode between women who took antidepressants and women who did not (hazard ratio [HR] = 0.88; 95% CI = 0.51-1.50). After accounting for antidepressant use, clearly hazardous factors included 4 or more depressive episodes before pregnancy (HR = 1.97; 95% CI = 1.09-3.57), black race (HR = 3.69; 95% CI = 2.16-6.30), and Hispanic ethnicity (HR = 2.33; 95% CI = 1.47-3.69). CONCLUSIONS: Failure to use or discontinuation of antidepressants in pregnancy did not have a strong effect on the development of a major depressive episode. Women with 4 or more episodes before pregnancy were at high risk of a major depressive episode, independent of antidepressant use. Black and Hispanic women also were at high risk of a major depressive episode, but it is possible that this effect is attributable to unmeasured factors.

Hormone therapy and fatal breast cancer.

PURPOSE: Among unanswered questions is whether menopausal use of estrogen therapy (ET) or estrogen-plus-progestin therapy (CHT) increases risk of developing fatal breast cancer i.e., developing and dying of breast cancer. Using a population-based case-control design, we estimated incidence rate ratios of fatal breast cancer in postmenopausal hormone therapy (HT) users compared to non-users by type, duration, and recency of HT use. METHODS: HT use prior to breast cancer diagnosis in 278 women who died of breast cancer within 6 years of diagnosis (cases) was compared with use in 2224 controls never diagnosed with breast cancer using conditional logistic regression. Measures taken to address potential bias and confounding inherent in case-control studies included collecting and adjusting for detailed data on demographic and other factors potentially associated both with HT use and breast cancer. RESULTS: Fifty-six per cent of cases and 68% of controls reported HT use. Among current 3+ year HT users, odds ratios and 95% confidence intervals for death were 0.83 (0.50, 1.38) and 0.69 (0.44, 1.09), respectively, for exclusive use of CHT or of ET, and were 0.94 (0.59, 1.48) and 0.70 (0.45, 1.07) for any use of CHT or of ET regardless of other hormone use. CONCLUSION: Point estimates suggest no increased risk of fatal breast cancer with HT use, although 50% increases in risk in longer-term current CHT users cannot be ruled out.

Timing of menarche and first full-term birth in relation to breast cancer risk.

Ages at menarche and first birth are established risk factors for breast cancer. The interval between these ages may also affect risk, since the breast is more susceptible to carcinogenic insults during this period than during the parous period. However, few investigators have studied this relation. Using logistic regression, the authors evaluated associations between the timing of reproductive events and breast cancer risk among 4,013 cases and 4,069 controls enrolled in a multicenter, population-based US case-control study of White and African-American women (1994-1998). For White, parous premenopausal and postmenopausal women, those who had an interval of > or =16 years between the ages of menarche and first birth had 1.5-fold (95% confidence interval (CI): 1.0, 2.2) and 1.4-fold (95% CI: 1.1, 1.8) increased risks of breast cancer, respectively, in comparison with those who had < or =5 years between these ages. Adjusting for age at first birth altered these risk estimates somewhat, to odds ratios of 1.5 (95% CI: 0.8, 2.9) and 1.0 (95% CI: 0.6, 1.5), respectively. These associations were stronger for lobular and hormone-receptor-positive tumors but were absent among premenopausal African-American women. The authors conclude that the interval between age at menarche and age at first birth is associated with the risk of hormonally sensitive types of breast cancer, particularly among White women.

Breast cancer risk and hormone receptor status in older women by parity, age of first birth, and breastfeeding: a case-control study.

BACKGROUND: Early age at first birth and multiparity reduce the risk of estrogen receptor-progesterone receptor (ERPR)-positive breast cancer, whereas breastfeeding reduces the risk of both ERPR-positive and ERPR-negative cancers. METHODS: We used multivariable logistic regression analysis to investigate whether age at first birth (<25 or > or =25 years) and breastfeeding (ever/never) modify the long-term effect of parity on risk of ERPR-positive and ERPR-negative cancer using 1,457 incident breast cancer cases and 1,455 controls ages > or =55 years who participated in the Women's Contraceptive and Reproductive Experiences Study. RESULTS: Women who gave birth before age 25 years had a 36% reduced risk of breast cancer compared with nulligravida that was not observed for women who started their families at an older age (P(heterogeneity) = 0.0007). This protective effect was restricted to ERPR-positive breast cancer (P(heterogeneity) = 0.004). Late age at first birth increased the risk of ERPR-negative cancers. Additional births reduced the risk of ERPR-positive cancers among women with an early first birth (P(trend) = 0.0001) and among women who breastfed (P(trend) = 0.004) but not among older mothers or those who never breastfed. In women with a late first birth who never breastfed, multiparity was associated with increased risk of breast cancer. CONCLUSIONS: These findings suggest that the effect of parity on a woman's long-term risk of breast cancer is modified by age at first full-term pregnancy and possibly by breastfeeding.

Longitudinal study of depot medroxyprogesterone acetate (Depo-Provera) effects on bone health in adolescents: study design, population characteristics and baseline bone mineral density.

BACKGROUND: This analysis was conducted to assess the baseline data and design methodology within an observational longitudinal comparison of use vs. nonuse of the injectable (intramuscular) contraceptive depot medroxyprogesterone acetate (DMPA-IM) and its effect on bone mass in adolescent women. STUDY DESIGN: A prospective, observational, open-label, unmatched-cohort, safety study in females aged 11-18 years. Participants either self-selected DMPA-IM (Depo-Provera) 150 mg to be administered every 12 weeks for up to 240 weeks with a 120-week post-treatment follow-up or were nonusers (users of nonhormonal contraception or sexually abstinent) who were to be followed up for up to 360 weeks. As each participant entered the study, bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry at the lumbar spine, hip and femoral neck regions, along with total body bone mineral content; serum and urine specimens were obtained for assay of bone metabolism markers and participants' histories of parity and tobacco and alcohol use were obtained. RESULTS: A total of 389 participants were enrolled: 169 elected to begin DMPA-IM; 26 chose nonhormonal methods and 194 were abstinent. The baseline characteristics indicated significant disparities between DMPA-IM users and nonusers: compared with the nonusers, DMPA-IM users had more advanced chronologic and gynecologic ages, were more likely to have smoked, been pregnant and included more blacks. These factors would likely influence bone accretion rates independent of DMPA-IM exposure. Comparison of participant BMDs with standard reference data revealed that the study cohorts did not match reference populations closely enough to make a direct between-cohort comparative analysis feasible. CONCLUSIONS: The baseline differences in cohort characteristics preclude a meaningful comparison of mean BMD changes over time between DMPA-IM users and nonusers cohorts, and comparisons of changes in Z-scores between cohorts were also not appropriate. Therefore, within-participant BMD decreases from baseline were established as safety thresholds, and the proportion of individuals crossing those thresholds on a persistent or progressive basis was identified as the revised primary end point.

Oral contraceptives and the risk of breast cancer.

BACKGROUND: It is uncertain whether the use of an oral contraceptive increases the risk of breast cancer later in life, when the incidence of breast cancer is increased. We conducted a population-based, case-control study to determine the risk of breast cancer among former and current users of oral contraceptives. METHODS: We interviewed women who were 35 to 64 years old. A total of 4575 women with breast cancer and 4682 controls were interviewed. Conditional logistic regression was used to calculate odds ratios as estimates of the relative risk (incidence-density ratios) of breast cancer. RESULTS: The relative risk was 1.0 (95 percent confidence interval, 0.8 to 1.3) for women who were currently using oral contraceptives and 0.9 (95 percent confidence interval, 0.8 to 1.0) for those who had previously used them. The relative risk did not increase consistently with longer periods of use or with higher doses of estrogen. The results were similar among white and black women. Use of oral contraceptives by women with a family history of breast cancer was not associated with an increased risk of breast cancer, nor was the initiation of oral-contraceptive use at a young age. CONCLUSIONS: Among women from 35 to 64 years of age, current or former oral-contraceptive use was not associated with a significantly increased risk of breast cancer.

Transdermal hormonal contraception: benefits and risks.

Transdermal drug delivery systems have been available in the United States for >20 years. Since the introduction of the first transdermal patch (scopolamine) for the treatment of motion sickness, >35 transdermal patch products have been approved by the US Food and Drug Administration for a variety of indications that include hormone replacement therapy, nicotine replacement therapy, chronic pain (fentanyl), angina (nitroglycerin), hypertension (clonidine), and more recently, overactive bladder (oxybutynin), and contraception (ethinyl estradiol/norelgestromin). Clinical data demonstrated the efficacy and safety of the contraceptive patch; however, concerns regarding estrogen levels and reports of venous thromboembolism led to the development of 2 epidemiologic studies and, subsequently, revised product labeling. Despite this, the contraceptive patch may be an appropriate option for some patients.

The transdermal contraceptive patch: an updated review of the literature.

The transdermal contraceptive patch which contains ethinyl estradiol and norelgestromin has an efficacy similar to current oral contraceptives (OCs). The major advantages include transdermal application and maintenance of adequate hormonal levels for at least 7 days. Side effects are similar to OC except for breast tenderness in the first 2 months of use and skin irritation at the application site. Although concern has been raised about a possible increased risk of venous thromboembolism, current available data comparing the patch to a norgestimate-containing OC ranges from no increase in risk to a 2.4-fold increase.

Effects of low-dose oral contraceptives on body weight: results of a randomized study of up to 13 cycles of use.

OBJECTIVE: To compare the effect of 2 oral contraceptives (OCs) on body weight. STUDY DESIGN: A randomized, parallel-group, multicenter study of 1,723 women taking an OC with norgestimate (NGM) 180/215/250 microg/ethinyl estradiol (EE) 25 microg vs. 1,171 women taking on OC with norethindrone acetate 1 mg/EE 20 microg for 6-13 cycles was performed. Body weight changes between baseline and cycle 6 and baseline and cycle 13 were analyzed. Analysis included not only changes in mean body weight but also the distribution of changes that were within 5% of baseline weight, 5-10% of baseline weight and > 10% of baseline weight. Only the 10% change was felt to be clinically significant. RESULTS: The distribution of body weight changes did not statistically differ between the 2 OC groups for any parameter measured. The mean weight change after 6 months for the NGM/EE and norethindrone acetate/EE groups was +0.71 kg and +0.57 kg, respectively. At 13 cycles for the NGM/EE and norethindrone acetate/ EE groups, the mean body weight change was +0.93 kg and +0.62 kg, respectively. Only 0.3% of subjects in both OC groups experienced a 10% change in weight. CONCLUSION: Use of OCs does not substantially affect body weight for most women.

Relationship between established breast cancer risk factors and risk of seven different histologic types of invasive breast cancer.

BACKGROUND: Important differences in the contributions of certain exposures to the risks of ductal versus lobular breast carcinomas have been observed, but few studies have evaluated the relationships between established breast cancer risk factors and other histologic types. METHODS: Information on family history of cancer and reproductive, hormonal, anthropometric, and lifestyle characteristics were collected in a multicenter population-based case-control study consisting of 3,463 ductal, 274 lobular, 261 ductal-lobular, 91 medullary, 77 tubular, 70 comedo, and 61 mucinous invasive breast carcinoma cases (ages 35-64 years, newly diagnosed 1994-1998) and 4,682 controls. Associations between each of these histologic types and various exposures were evaluated using polytomous regression. RESULTS: Heterogeneity in the risks of different histologic types of breast cancer was observed for three exposures: menopausal hormone use, body mass index (BMI), and alcohol consumption. Specifically, current use of unopposed estrogen was associated with a reduced risk of ductal carcinoma and increased risk of comedocarcinoma, and current use of estrogen and progestin was associated with elevated risks of ductal-lobular and tubular carcinomas. Among postmenopausal women, BMI was only inversely related to risk of ductal-lobular carcinoma, and alcohol use was only positively related to risk of lobular carcinoma. CONCLUSIONS: Variations in the associations between known breast cancer risk factors and risk of different breast cancer histologies were observed. Although these findings require confirmation, and the analyses of some histologic groups were limited by small sample sizes, they provide some insight into the different etiologies of various histologic subtypes of breast cancer.

The Evolving Role of Midwives as Laborists.

This article examines the history and present state of the midwife as laborist. The role of the midwife and obstetrician laborist/hospitalist is rapidly evolving due to the need to improve patient safety and provide direct care due to reduced resident work hours, as well as practice demands experienced by community providers and other factors. Models under development are customized to meet the needs of different communities and hospitals. Midwives are playing a prominent role in many laborist/hospitalist practices as the first-line hospital provider or as part of a team with physicians. Some models incorporate certified nurse-midwives/certified midwives as faculty to residents and medical students. The midwifery laborist/hospitalist practices at Baystate Medical Center in Springfield, Massachusetts, are presented as an example of how midwives are functioning as laborists. Essential components of a successful midwife laborist program include interdisciplinary planning, delineation of problems the model should solve, establishment of program metrics, clear practice guidelines and role definitions, and a plan for sustained funding. This article is part of a special series of articles that address midwifery innovations in clinical practice, education, interprofessional collaboration, health policy, and global health.

Alcohol exposure and breast cancer: results of the women's contraceptive and reproductive experiences study.

OBJECTIVES: To explore associated biological outcomes and clarify the role of timing of exposure in the alcohol-breast cancer relationship. METHODS: In a population-based study of 4,575 women ages 35 to 64 years diagnosed with invasive breast cancer between 1994 and 1998 and 4,682 controls, we collected details of lifetime alcohol use and factors that could confound or modify the alcohol-breast cancer relationship. We used conditional logistic regression to compute the odds of breast cancer among drinkers relative to nondrinkers at all ages and at ages 35 to 49 and 50 to 64 years separately. RESULTS: Recent consumption (at reference age minus two) of >/=7 drinks per week was associated with increased risk [odds ratio (OR), 1.2; 95% CI, 1.01-1.3] and evidence of dose response was observed. Most of the excess was observed among women ages 50-64 years (OR 1.3; 95% CI, 1.1-1.6), although the test for age interaction was not statistically significant. Exposure later in life seemed more important than early exposure. Excess breast cancer associated with recent consumption was restricted to localized disease. When outcome was examined according to tumor hormone receptor status, highest risks were observed for estrogen receptor-positive/progesterone receptor-negative tumors (OR 1.6; 95% CI, 1.2-2.3). CONCLUSIONS: The effect of timing of alcohol exposure on breast cancer risk is complicated and will require additional study focused on this one issue. Further work is needed to explain how alcohol exposure, sex hormones, and tumor receptor status interact.

Do thyroid disorders increase the risk of breast cancer?

The objective of this study was to determine whether thyroid disorders or treatment of such disorders affects the risk of breast cancer. Subjects aged 35-64 years were participants in the National Institute of Child Health and Human Development Women's Contraceptive and Reproductive Experiences Study, a population-based, case-control study of invasive breast cancer that was carried out at five sites in the United States. In-person interviews were completed for 4575 women (cases) with breast cancer (2953 white and 1622 black) and 4682 control women (3021 white and 1661 black). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using multiple logistic regression methods. Models included adjustment for age (5-year age groups), race (white or black), and site. A history of any thyroid disorder (OR = 1.1, 95% CI = 0.9-1.2) was not associated with breast cancer risk. Only women with a history of thyroid cancer had an increased risk, but this was restricted to parous women (parous OR = 3.4, 95% CI = 1.5-8.1; nulliparous OR = 0.5, 95% CI = 0.04-5.1). Breast cancer risk was not associated with treatment for thyroid disorders. There was no statistical interaction between thyroid disorders, thyroid treatments, and race, menopausal status, or parity. We found no association between thyroid disorders or their associated treatments and the risk of breast cancer.

Association of regimens of hormone replacement therapy to prognostic factors among women diagnosed with breast cancer aged 50-64 years.

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.

The NICHD Women's Contraceptive and Reproductive Experiences Study: methods and operational results.

PURPOSE: This paper presents methods and operational results of a population-based case-control study examining the effects of oral contraceptive use on breast cancer risk among white and black women aged 35-64 years in five U.S. locations. METHODS: Cases were women newly diagnosed with breast cancer during July 1994 through April 1998. Controls were identified through random digit dialing (RDD) using unclustered sampling with automated elimination of nonworking numbers. Sampling was density-based, with oversampling of black women. In-person interviews were conducted from August 1994 through December 1998. Blood samples were obtained from subsets of cases and controls, and tissue samples were obtained from subsets of cases. A computerized system tracked subjects through study activities. Special attention was devoted to minimizing exposure misclassification, because any exposure-disease associations were expected to be small. RESULTS: An estimated 82% of households were screened successfully through RDD. Interviews were completed for 4575 cases (2953 whites; 1622 blacks) and 4682 controls (3021 whites; 1661 blacks). Interview response rates for cases and controls were 76.5% and 78.6%, respectively, with lower rates for black women and older women. CONCLUSIONS: The methodologic details of this large collaboration may assist researchers conducting similar investigations.

Hormone replacement therapy regimens and breast cancer risk(1).

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.