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.

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.

Fifty years of "the pill": risk reduction and discovery of benefits beyond contraception, reflections, and forecast.

Widely regarded as a revolutionary drug in its early years, "the pill" may be considered the first designer or lifestyle drug. Approximately 85% of women in the United States will use an oral contraceptive (OC) for an average of 5 years. Since the introduction of OCs in the 1960s, both health benefits and safety concerns have been attributed to their use. Widespread use of OC formulations by women throughout their reproductive life cycle gave rise to concerns about the effects of OCs on risk factors for cardiovascular disorders and cancer. In most instances, the noncontraceptive benefits of OCs outweigh the potential risks. As with many first in class drugs, lessons can be learned from its development and use. Indeed, "the pill" played a significant role in reshaping the regulatory process for new drugs during the second half of the 20th century. The birth control pill celebrates its 50th birthday this year, as women and men celebrate five decades of this revolutionary method of family planning. Recent scientific and technological advances in genomics, proteomics, new materials, and new drug delivery systems, along with a new understanding of reproductive biology, offer the promise of new, safe, and effective forms of contraception. In addition to the history of OC therapeutic advances and unintended side effects, the noncontraceptive health benefits that women experience beyond pregnancy prevention are discussed. This article summarizes a symposium presented at the 50th Anniversary of the Society of Toxicology National Meeting, held from 6 to 10 March 2011 in Washington, DC.

Oral contraceptive formulation and risk of breast cancer.

BACKGROUND: While evidence on the association between oral contraceptive (OC) use and breast cancer generally suggests little or no increased risk, the question of whether breast cancer risk varies by OC formulation remains controversial. Few studies have examined this issue because large samples and extensive OC histories are required. STUDY DESIGN: We used data from a multicenter, population-based, case-control investigation. Women aged 35-64 years were interviewed. To explore the association between OC formulation and breast cancer risk, we used conditional logistic regression to derive adjusted odds ratios, and we used likelihood ratio tests for heterogeneity to assess whether breast cancer risk varied by OC formulation. Key OC exposure variables were ever use, current or former use, duration of use and time since last use. To strengthen inferences about specific formulations, we restricted most analyses to the 2282 women with breast cancer and the 2424 women without breast cancer who reported no OC use or exclusive use of one OC. RESULTS: Thirty-eight formulations were reported by the 2674 women who used one OC; most OC formulations were used by only a few women. We conducted multivariable analyses on the 10 formulations that were each used by at least 50 women and conducted supplemental analyses on selected formulations of interest based on recent research. Breast cancer risk did not vary significantly by OC formulation, and no formulation was associated with a significantly increased breast cancer risk. CONCLUSIONS: These results add to the small body of literature on the relationship between OC formulation and breast cancer. Our data are reassuring in that, among women 35-64 years of age, we found no evidence that specific OC formulations increase 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.

Making it work: successful collaborative practice.

There are three major examples of collaborative programs between certified nurse-midwives (CNMs) and obstetrician-gynecologists at Baystate Medical Center in Springfield, Massachusetts, within the Department of Obstetrics and Gynecology. One program is a midwifery practice that serves a diverse population in a hospital-based office, four neighborhood health centers, and a correctional facility. Another program provides a triage function for patients who present to the hospital with obstetric or gynecologic problems. The third program introduces a team approach to the education of residents with a CNM having primary responsibility for teaching normal obstetrics to first-year residents and medical students in collaboration with attending physicians. Keys to success include an understanding of the principles of collaborative practice, the use of a detailed practice agreement between midwives and attending physicians, keeping open lines of communication, understanding and accepting differing philosophies of practice, and, most importantly, maintaining trust across all levels of providers.

Obesity and survival among black women and white women 35 to 64 years of age at diagnosis with invasive breast cancer.

PURPOSE: To evaluate the effect of obesity on survival among black women and white women with invasive breast cancer and to determine whether obesity explains the poorer survival of black women relative to white women. PATIENTS AND METHODS: We observed 4,538 (1,604 black, 2,934 white) women who were 35 to 64 years of age when diagnosed with incident invasive breast cancer between 1994 and 1998. Multivariate Cox regression models were used to examine the effect of body mass index (BMI, in kilograms per square meter) 5 years before diagnosis on risk of death from any cause and from breast cancer. RESULTS: During a median of 8.6 years of follow-up, 1,053 women died (519 black, 534 white), 828 as a result of breast cancer (412 black, 416 white). Black women were more likely to die than white women (multivariate-adjusted relative risk [RR], 1.33; 95% CI, 1.16 to 1.53). Compared with women with BMI of 20 to 24.9 kg/m(2), those who were obese (BMI ≥ 30 kg/m(2)) had a greater risk of all-cause mortality (RR, 1.23; 95% CI, 1.04 to 1.47) and breast cancer-specific mortality (RR, 1.20; 95% CI, 0.99 to 1.46). These associations were observed among white women (all-cause RR, 1.54; 95% CI, 1.21 to 1.96; breast cancer RR, 1.46; 95% CI, 1.11 to 1.92), but not among black women (all-cause RR, 1.03; 95% CI, 0.81 to 1.29; breast cancer RR, 1.02; 95% CI, 0.79 to 1.33). CONCLUSION: Obesity may play an important role in mortality among white but not black patients with breast cancer. It is unlikely that differences in obesity distributions between black women and white women account for the poorer survival of black women.

A comparison of obstetric maneuvers for the acute management of shoulder dystocia.

OBJECTIVE: To assess the efficacy of obstetric maneuvers for resolving shoulder dystocia and the effect that these maneuvers have on neonatal injury when shoulder dystocia occurs. METHODS: Using an electronic database encompassing 206,969 deliveries, we identified all women with a vertex fetus beyond 34 0/7 weeks of gestation who incurred a shoulder dystocia during the process of delivery. Women whose fetuses had a congenital anomaly and women with an antepartum stillbirth were excluded. Medical records of all cases were reviewed by trained abstractors. Cases involving neonatal injury (defined as brachial plexus injury, clavicular or humerus fracture, or hypoxic-ischemic encephalopathy or intrapartum neonatal death attributed to the shoulder dystocia) were compared with those without injury. RESULTS: Among 132,098 women who delivered a term cephalic liveborn fetus vaginally, 2,018 incurred a shoulder dystocia (1.5%), and 101 (5.2%) of these incurred a neonatal injury. Delivery of the posterior shoulder was associated with the highest rate of delivery when compared with other maneuvers (84.4% compared with 24.3-72.0% for other maneuvers; P<.005 to P<.001) and similar rates of neonatal injury (8.4% compared with 6.1-14.0%; P=.23 to P=.7). The total number of maneuvers performed significantly correlated with the rate of neonatal injury (P<.001). CONCLUSION: Delivery of the posterior shoulder should be considered following the McRoberts maneuver and suprapubic pressure in the management of shoulder dystocia. The need for additional maneuvers was associated with higher rates of neonatal injury.

Characteristics associated with severe perineal and cervical lacerations during vaginal delivery.

OBJECTIVE: To characterize potentially modifiable risk factors for third- or fourth-degree perineal lacerations and cervical lacerations in a contemporary U.S. obstetric practice. METHODS: The Consortium on Safe Labor collected electronic medical records from 19 hospitals within 12 institutions (228,668 deliveries from 2002 to 2008). Information on patient characteristics, prenatal complications, labor and delivery data, and maternal and neonatal outcomes were collected. Only women with successful vaginal deliveries of cephalic singletons at 34 weeks of gestation or later were included; we excluded data from sites lacking information about lacerations at delivery and deliveries complicated by shoulder dystocia; 87,267 and 71,170 women were analyzed for third- or fourth-degree and cervical lacerations, respectively. Multivariable logistic regressions were used to adjust for other factors. RESULTS: Third- or fourth-degree lacerations occurred in 2,516 women (2,223 nulliparous [5.8%], 293 [0.6%] multiparous) and cervical lacerations occurred in 536 women (324 nulliparous [1.1%], 212 multiparous [0.5%]). Risks for third- or fourth-degree lacerations included nulliparity (7.2-fold risk), being Asian or Pacific Islander, increasing birth weight, operative vaginal delivery, episiotomy, and longer second stage of labor. Increasing body mass index was associated with fewer lacerations. Risk factors for cervical lacerations included young maternal age, vacuum vaginal delivery, and oxytocin use among multiparous women, and cerclage regardless of parity. CONCLUSION: Our large cohort of women with severe obstetric lacerations reflects contemporary obstetric practices. Nulliparity and episiotomy use are important risk factors for third- or fourth-degree lacerations. Cerclage increases the risk for cervical lacerations. Many identified risk factors may not be modifiable.

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.

A case-control study of body mass index and breast cancer risk in white and African-American women.

OBJECTIVE: Large body size has been associated with decreased risk of breast cancer in premenopausal women but with increased risk in postmenopausal women. Limited information is available about African-American women and differences by estrogen and progesterone receptor status. METHODS: We analyzed data from the Women's Contraceptive and Reproductive Experiences Study among 3,997 white and African-American breast cancer case patients diagnosed in 1994 to 1998 and 4,041 control participants ages 35 to 64 years. We calculated multivariate odds ratios (OR) as measures of relative risk of breast cancer associated with self-reported body mass index (BMI) at age 18 and 5 years before diagnosis (recent BMI). RESULTS: Risk tended to decrease with increasing BMI at age 18 years in all women [OR(BMI > or = 25 kg/m(2) versus < 20 kg/m(2)) = 0.76; 95% confidence interval (CI), 0.63-0.90; P(trend) = 0.005] and with recent BMI in premenopausal women (OR(BMI > or = 35 kg/m(2) versus < 25 kg/m(2)) = 0.81; 95% CI, 0.61-1.06; P(trend) = 0.05), unmodified by race. Among postmenopausal white but not African-American women, there was an inverse relation between recent BMI and risk. High recent BMI was associated with increased risk of estrogen receptor- and progesterone receptor-positive tumors among postmenopausal African-American women (OR(BMI > or = 35 kg/m(2) versus < 25 kg/m(2)) = 1.83; 95% CI, 1.08-3.09; P(trend) = 0.03). CONCLUSION: Among women at age 35 to 64 years, BMI at age 18 years is inversely associated with risk of breast cancer, but association with recent BMI varies by menopause status, race, and hormone receptor status. IMPACT: Our findings indicate that studies of BMI and breast cancer should consider breast cancer subtypes.

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.

Use of four biomarkers to evaluate the risk of breast cancer subtypes in the women's contraceptive and reproductive experiences study.

Epidemiologic studies suggest that some hormone-related risk factors in breast cancer differentially influence risk for disease subtypes classified by the status of the estrogen and progesterone receptors (ER/PR). However, it remains unclear whether human epidermal growth factor receptor 2 (HER2) or p53 expression status further differentiates these exposure-risk group associations. We evaluated the associations of oral contraceptive (OC) use and reproductive factors with incident invasive breast cancer subtypes among 1,197 population-based cases and 2,015 controls from the Los Angeles County or Detroit components of the Women's Contraceptive and Reproductive Experiences Study. Case-control comparisons by ER/PR/HER2/p53 status were conducted by multivariable polychotomous unconditional logistic regression methods. We found that OC use was not associated with any breast cancer subtype as defined by ER/PR/HER2/p53 status, except for a 2.9-fold increased risk of so-called triple-negative tumors (ER(-)/PR(-)/HER2(-)) among women of 45 to 64 years of age who started OC use before age 18. Parity was associated with a decreased risk of luminal A (ER(+) or PR(+), HER2(-)), luminal B (ER(+) or PR(+)/HER2(+)), and ER(-)/PR(-)/HER2(+) tumors. Age at first full-term pregnancy was positively associated with luminal A tumors among older women. Neither of these reproductive factors was associated with triple-negative tumors. Long duration of breast-feeding lowered the risk of triple-negative and luminal A tumors. p53 status did not define further differential risk patterns. Our findings offer evidence of differences in the hormone-related risk factors between triple-negative cancers and other ER/PR/HER2-defined subtypes of breast cancer.

Cycle control with a 21-day compared with a 24-day oral contraceptive pill: a randomized controlled trial.

OBJECTIVE: To compare bleeding patterns between a 21/7-day triphasic norgestimate/ethinyl estradiol (E2) 25-microgram oral contraceptive pill (OCP) and a 24/4-day drospirenone/ethinyl E2 20-microgram OCP. METHODS: In a three-cycle, open-label, multicenter study, healthy, sexually active women were assigned randomly to a 21/7-day (norgestimate/ethinyl E2) or 24/4-day (drospirenone/ethinyl E2) OCP regimen. Randomization was stratified to assure a balanced distribution between regimens for "fresh starts" and "switchers." Bleeding data were collected daily using an interactive voice-response system. Bleeding was defined according to the 2007 U.S. Food and Drug Administration's Reproductive Health Drug Advisory Committee-endorsed criteria. RESULTS: Across the three cycles, the 21/7-day OCP group (n=165) reported fewer unscheduled bleeding days than did the 24/4-day OCP group (n=167) (mean 4.6 compared with 6.1 days, P=.003). Women using the 21/7-day OCP had significantly fewer episodes of unscheduled bleeding than did those using the 24/4-day OCP (mean 1.47 compared with 2.01, P=.001). Moreover, women using the 21/7-day OCP had a significantly lower absence of scheduled bleeding at each cycle (P<.001). Both regimens were well-tolerated. CONCLUSION: A 21-day norgestimate/ethinyl E2 25-microgram regimen results in less unscheduled bleeding and more scheduled bleeding than does a 24-day drospirenone/ethinyl E2 20-microgram regimen. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.ClinicalTrials.gov, NCT00745901. LEVEL OF EVIDENCE: I.

Breast cancer receptor status: do results from a centralized pathology laboratory agree with SEER registry reports?

We investigated the extent to which estrogen receptor (ER) and progesterone receptor (PR) status results from a centralized pathology laboratory agree with ER and PR results from community pathology laboratories reported to two Surveillance, Epidemiology and End Results (SEER) registries (Los Angeles County and Detroit) and whether statistical estimates for the association between reproductive factors and breast cancer receptor subtypes differ by the source of data. The agreement between the centralized laboratory and SEER registry classifications was substantial for ER (kappa = 0.70) and nearly so for PR status (kappa = 0.60). Among the four subtypes defined by joint ER and PR status, the agreement between the two sources was substantial for the two major breast cancer subtypes (ER-/PR-, kappa = 0.69; ER+/PR+, kappa = 0.62) and poor for the two rarer subtypes (ER+/PR-, kappa = 0.30; ER-/PR+, kappa = 0.05). Estimates for the association between reproductive factors (number of full-term pregnancies, age at first full-term pregnancy, and duration of breastfeeding) and the two major subtypes (ER+/PR+ and ER-/PR-) differed minimally between the two sources of data. For example, parous women with at least four full-term pregnancies had 40% lower risk for ER+/PR+ breast cancer than women who had never been pregnant [centralized laboratory, odds ratio, 0.60 (95% confidence interval, 0.39-0.92); SEER, odds ratio, 0.57 (95% confidence interval, 0.38-0.85)]; no association was observed for ER-/PR- breast cancer (both P(trend) > 0.30). Our results suggest that conclusions based on SEER registry data are reasonably reliable for ER+/PR+ and ER-/PR- subtypes.

Relationship between migraine history and breast cancer risk among premenopausal and postmenopausal women.

Both migraine and breast cancer are hormonally mediated diseases, and it is biologically plausible that women with a history of migraine may have a reduced breast cancer risk. However, this relationship has only been assessed in a single relatively small study that was unable to assess the effect of migraine triggers, which are also well-established breast cancer risk factors (e.g., use of alcohol and exogenous hormones), on the inverse association observed. Utilizing data on 4,568 breast cancer cases and 4,678 controls who participated in a multicenter population-based case-control study in the United States, we evaluated the association between migraine history and breast cancer risk using unconditional logistic regression. Migraine history data were obtained from structured in-person interviews. Women with a history of migraine had a reduced risk of breast cancer [odds ratio, 0.74; 95% confidence interval (CI), 0.66-0.82]. This risk did not differ by menopausal status, age at migraine diagnosis, use of prescription migraine medications, or when analyses were restricted to women who avoided various migraine triggers (including alcohol, exogenous hormones, and smoking). These data support a previous finding that a history of migraine may be associated with a reduced risk of breast cancer. It extends the prior report in observing that this relationship holds for both premenopausal and postmenopausal women and is independent of exposure to common migraine triggers.

Association between efficacy and body weight or body mass index for two low-dose oral contraceptives.

BACKGROUND: This analysis investigated the association of oral contraceptive efficacy with body weight and body mass index (BMI) for hypothesis-generating purposes. STUDY DESIGN: Data were from a randomized, parallel-group trial of 180/215/250 mcg of norgestimate (NGM)/25 mcg of ethinyl estradiol (EE) (given to 1671 women) and 1 mg of norethindrone acetate (NETA)/20 mcg of EE (given to 1139 women). Pregnancies were evaluated across BMI deciles and by BMI and body weight dichotomies. A Pearl index was calculated for each treatment group. The relative risk (RR) of pregnancy was calculated with a Cox proportional hazards model. RESULTS: The Pearl index for women who received NGM/EE was 2.36 [95% confidence interval (CI)=1.33-3.40]; for those who received NETA/EE, the Pearl index was 3.29 (95% CI=1.81-4.77). Consistent, weak positive associations between weight and pregnancy risk were found. Overall, for women with a BMI >or=25 kg/m(2) (compared with women with a BMI <25 kg/m(2)), the RR of pregnancy was 1.84 (95% CI=0.98-3.45); that for women who received NGM/EE was 1.39 (95% CI=0.57-3.40), whereas that for women who received NETA/EE was 2.49 (95% CI=1.01-6.13). For women with a body weight >or=70 kg (compared with women with a body weight <70 kg), the RR was 1.25 (95% CI=0.63-2.46); that for women who received NGM/EE was 1.41 (95% CI=0.56-3.54), whereas that for women who received NETA/EE was 1.12 (95% CI=0.40-3.12). CONCLUSION: Women in the higher body weight or BMI category showed a small increase in the risk of pregnancy with these oral contraceptives, but this increase was not statistically significant overall or for either formulation studied.