Early menarche predicts incidence of asthma in early adulthood

The present study explores the effect of age at menarche on the incidence of asthma during early adulthood. The analysis was based on Canadian girls followed up from 8-11 to 18-21 years of age during the first 6 cycles (1994-2005) of the National Longitudinal Survey of Children and Youth. Early menarche was defined as 1 standard deviation less than the average age at menarche. Asthma occurrence after menarche was measured as asthma that was diagnosed by a health care professional. The authors used logistic regression to investigate the association between early menarche and incidence of asthma, adjusting for possible confounders. A total of 1,176 girls weighted to represent 352,345 Canadian girls were analyzed. The incidence of asthma after menarche was 11.2% (95% confidence interval: 8.3, 14.0). The onset of early menarche (<11.56 years of age) predicted postmenarcheal incidence of asthma; girls who matured early had more than twice the risk of developing asthma during early adulthood than did girls who matured at an average age (odds ratio, 2.34, 95% confidence interval: 1.19, 4.59). The present study provides partial insight into the worldwide rapid increase in asthma rates that coincides with the declining trends in menarcheal timing. Further studies within different contexts are warranted to assess the generalizability of these Canadian findings.     

Childhood growth and breast cancer

Adult height is known to be positively associated with breast cancer risk. The mechanism underlying this association is complex, since adult height is positively correlated with age at menarche, which in turn is negatively associated with breast cancer risk. The authors used prospective data from a British cohort of 2,547 girls followed from birth in 1946 to the end of 1999 to examine breast cancer risk in relation to childhood growth. As expected, adult height was positively associated with age at menarche and breast cancer. In childhood, cases were taller and leaner, on average, than noncases. Significant predictors of breast cancer risk in models containing all components of growth were height velocity at age 4-7 years (for a one-standard-deviation increase, odds ratio (OR) = 1.54, 95% confidence interval (CI): 1.13, 2.09) and age 11-15 years (OR = 1.29, 95% CI: 0.97, 1.71) and body mass index velocity (weight (kg)/height (m)(2)/year) at age 2-4 years (OR = 0.63, 95% CI: 0.48, 0.83). The effects of these variables were particularly marked in women with early menarche (age <12.5 years). These findings suggest that women who grow faster in childhood and reach an adult height above the average for their menarche category are at particularly increased risk of breast cancer.     

Age at menarche in relation to maternal use of tobacco, alcohol, coffee, and tea during pregnancy

To investigate the potential effects of common early life exposures on age at menarche, the authors examined data collected in a follow-up study of pregnancies that occurred during the 1960s in California. Among 994 female offspring interviewed as adolescents, 98% had started their menstrual periods at a mean age of 12.96 years. After adjustment, the mean age at menarche was a few months earlier among girls whose mothers smoked a pack or more of cigarettes daily during pregnancy compared with unexposed girls (difference = -0.22 years, 95% confidence interval (CI): -0.49, 0.05) and more so among girls who were not White (difference = -0.52 years, 95% CI: -1.1, 0.08). Girls with both high prenatal and childhood passive smoke exposure had an adjusted mean age at menarche about 4 months earlier than those unexposed. The daughter's mean age at menarche varied little by maternal prenatal alcohol consumption. Daughters of tea consumers had a later mean age (difference = 0.41 years at >/= 3 cups (0.7 liter)/day, 95% CI: 0.03, 0.80) and were more likely to start menarche later (>13 years) (odds ratio = 1.7, 95% CI: 0.91, 3.2), but daughters of coffee consumers did not. These suggestive findings, which merit further investigation, may be related to hormonal effects.     

Relation of childhood height and later risk of breast cancer

The authors sought to examine the hypothesis that girls who were relatively tall during the prepubescent period (indicative of an affluent diet and good general health) were at increased risk of subsequent breast cancer. They conducted a case-control study of 214 long-term members who were diagnosed with breast cancer during 1973-1995 and who were age 12 years or younger when they first joined Kaiser Permanente and of 214 appropriately matched controls. Information was obtained from the medical records. While the authors observed the expected association of adult height with risk of breast cancer (height at age 15-18 years, tall-for-age vs. short-for-age: odds ratio = 2.2, 95% confidence interval: 1.1, 4.3), the association was no stronger earlier in life (height at age 9-11 years: odds ratio = 1.0, 95% confidence interval: 0.5, 1.8). The study does not support a relation between pubertal skeletal growth and adult risk of breast cancer. However, it is limited by the inclusion of few postmenopausal women.     

Childhood Abuse and Age at Menarche

PurposePhysical and sexual abuse are prevalent social hazards. We sought to examine the association between childhood physical and sexual abuse and age at menarche.MethodsAmong 68,505 participants enrolled in the Nurses' Health Study II, we investigated the association between childhood physical abuse and sexual abuse and menarche before age 11 years (early) or after age 15 years (late) using multivariate logistic regression analysis, mutually adjusting for both types of abuse.ResultsFifty-seven percent of respondents reported some form of physical or sexual abuse in childhood. We found a positive dose–response association between severity of sexual abuse in childhood and risk for early menarche. Compared with women who reported no childhood sexual abuse, the adjusted odds ratio (AOR) for early menarche in women who reported childhood sexual abuse was 1.20 (95% confidence interval [CI]: 1.10, 1.37) for sexual touching and 1.49 (95% CI: 1.34, 1.66) for forced sexual activity. Severe physical abuse predicted early menarche (AOR = 1.22, 95% CI: 1.10, 1.37). Childhood physical abuse had a dose–response association with late age at menarche: AOR 1.17 (95% CI: 1.04, 1.32) for mild, 1.20 (95% CI: 1.08, 1.33) for moderate, and 1.50 (95% CI: 1.27, 1.77) for severe physical abuse. Sexual abuse was not associated with late menarche.ConclusionsChildhood abuse was prevalent in this large cohort of U.S. women. Severity of childhood sexual abuse was associated with risk for early onset of menarche, and physical abuse was associated with both early and late onset of menarche.     

A prospective study of childhood social hardships and age at menarche

PurposeTo determine the role of type, timing, and cumulative childhood hardships on age at menarche in a prospective cohort study.MethodsA longitudinal analysis was undertaken of 4524 female participants of the National Child Development Study cohort (1958–2003). Six types of childhood hardships were identified with a factor analysis methodology. Paternal absence/low involvement in childhood was an a priori hardship. Retrospective reports of abuse in childhood also were explored in relation to age at menarche. Generalized logit regression analyses explored the impact of type, timing, and cumulative hardships on age at menarche (≤11, 12–13, ≥14 years).ResultsCumulative childhood hardships were associated with a graded increase in risk for later menarche with adjusted odds ratio [AOR] of 1.37 (95% confidence interval [95% CI], 1.10–1.70), 1.50 (95% CI, 1.18–1.91), and 1.58 (95% CI, 1.29–1.92) among those with two, three, and four or more adversities, respectively. More than two hardships in early life had the strongest association with late menarche (AOR, 2.32; 95% CI, 1.12–4.80). Sexual abuse was most strongly associated with early menarche (AOR, 2.60; 95% CI, 1.40–4.81).ConclusionsCumulative childhood hardships increased risk for later age at menarche. Child abuse was associated with both early and late menarche, although associations varied by type of abuse.     

Reproductive and menstrual risk factors for pancreatic cancer: a population-based study of San Francisco Bay Area women

Study results regarding risks associated with reproductive characteristics and pancreatic cancer have been mixed. Using data from a population-based case-control study of pancreatic cancer, the authors assessed the role of menstrual factors, reproductive factors, and hormone use in the etiology of pancreatic cancer among women (241 cases, 818 controls). Rapid case ascertainment was used in six San Francisco Bay Area counties in California between 1995 and 1999. Controls were sampled by using random digit dialing. All statistical tests were two sided. Age at menopause (> or = 45 years vs. < 45 years) was associated with a 1.8-fold increased risk of pancreatic cancer (95% confidence interval: 1.2, 2.8). No association was found between age at menarche, parity, oral contraceptive use, estrogen replacement therapy (ERT), or history of oophorectomy and pancreatic cancer. The adjusted odds ratio for current smoking and pancreatic cancer was stronger for women who had never used oral contraceptives or ERT (odds ratio = 11.5, 95% confidence interval: 3.5, 38.1) than for those who reported using both (odds ratio = 1.7, 95% confidence interval: 0.56, 5.0). Other than a possible reduced risk estimate for smoking-related pancreatic cancer for users of exogenous hormones (oral contraceptives and ERT), results did not show a consistent pattern for reproductive factors, estrogen exposure, and risk of pancreatic cancer.     

Body mass index at age 18 years and during adult life and ovarian cancer risk

During the years 1994-1999, a nationwide ovarian cancer case-control study was conducted in Israel. The present analysis addresses the question: Is epithelial ovarian cancer associated with body mass index at age 18 years and/or with weight changes in body mass index between adolescence and adult life? The study is based on 1,269 women with epithelial ovarian cancer and 2,111 matched controls. A significant decrease in risk of ovarian cancer was observed with parity, oral contraceptive use, and postmenopausal status. A significant increase in risk with family history of ovarian/breast cancer was also found. No significant association with age at menarche or infertility was found. For body mass index at age 18 years, the odds ratio of the highest versus lowest body mass index quartile was 1.42 (95% confidence interval: 1.08, 1.85) and after adjusting for confounders was 1.54 (95% confidence interval: 1.17, 2.02). However, no statistically significant risk associated with change in weight from age 18 years to adult life was found. The authors conclude that, in their population, body mass index at age 18 years is an independent risk factor for ovarian cancer.     

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.     

Dieting and smoking initiation in early adolescent girls and boys: a prospective study

OBJECTIVES: This analysis tested the relation between dieting frequency and risk of smoking initiation in a longitudinal sample of adolescents. METHODS: From 1995 to 1997, 1295 middle school girls and boys participated in a nutrition and physical activity intervention study. The prospective association between dieting frequency at baseline and smoking initiation 2 years later was tested. RESULTS: Compared with girls who reported no dieting at baseline, girls who dieted up to once per week had 2 times the adjusted odds of becoming smokers (odds ratio = 2.0; 95% confidence interval = 1.1, 3.5), and girls who dieted more often had 4 times the adjusted odds of becoming smokers (odds ratio = 3.9; 95% confidence interval = 1.5, 10.4). CONCLUSIONS: Dieting among girls may exacerbate risk of initiating smoking, with increasing risk with greater dieting frequency.     

Effects of environmental tobacco smoke on lower respiratory system of children under 5 years of age

OBJECTIVE: To determine the effects of second-hand smoke in the respiratory system of children under 5 years old. METHODS: A cross sectional study of a total of 1,104 children under 5 years old. Information about respiratory symptoms and illness, family history of respiratory diseases, smoking habits of household members and housing conditions were assessed by home interviews with the children's parents. RESULTS: We studied 546 boys and 558 girls. Among 611 children exposed to second-hand smoke, 82% had respiratory problems (odds ratio = 1.64; 95% confidence interval: 1.21-2.20). Children whose parents were smokers at the time of the survey were more likely to experience wheezing than children of nonsmoking parents (odds ratio = 1.66; 95% confidence interval: 1.21-2.27), shortness of breath (odds ratio = 1.91; 95% confidence interval: 1. 36-2.67), morning and day time or night coughs (odds ratio = 1.58; 95% confidence interval: 1.09-2.28). The odds ratio for asthma, bronchitis and pneumonia was greater for children exposed to second-hand smoke (odds ratio = 1.60; 95% confidence interval: 1. 11-2.31). CONCLUSIONS: Maternal smoking, paternal smoking, family history of respiratory diseases, and housing conditions are considered risk factors for respiratory diseases in children.     

Early-life soy exposure and age at menarche

This study examines the timing of menarche in relation to infant-feeding methods, specifically addressing the potential effects of soy isoflavone exposure through soy-based infant feeding. Subjects were participants in the Avon Longitudinal Study of Parents and Children (ALSPAC). Mothers were enrolled during pregnancy and their children have been followed prospectively. Early-life feeding regimes, categorised as primarily breast, early formula, early soy and late soy, were defined using infant-feeding questionnaires administered during infancy. For this analysis, age at menarche was assessed using questionnaires administered approximately annually between ages 8 and 14.5. Eligible subjects were limited to term, singleton, White females. We used Kaplan-Meier survival curves and Cox proportional hazards models to assess age at menarche and risk of menarche over the study period. The present analysis included 2920 girls. Approximately 2% of mothers reported that soy products were introduced into the infant diet at or before 4 months of age (early soy). The median age at menarche [interquartile range (IQR)] in the study sample was 153 months [144-163], approximately 12.8 years. The median age at menarche among early soy-fed girls was 149 months (12.4 years) [IQR, 140-159]. Compared with girls fed non-soy-based infant formula or milk (early formula), early soy-fed girls were at 25% higher risk of menarche throughout the course of follow-up (hazard ratio 1.25 [95% confidence interval 0.92, 1.71]). Our results also suggest that girls fed soy products in early infancy may have an increased risk of menarche specifically in early adolescence. These findings may be the observable manifestation of mild endocrine-disrupting effects of soy isoflavone exposure. However, our study is limited by few soy-exposed subjects and is not designed to assess biological mechanisms. Because soy formula use is common in some populations, this subtle association with menarche warrants more in-depth evaluation in future studies.     

Update on Age at Menarche in Italy: Toward the Leveling Off of the Secular Trend

PurposeTo update the information on age at menarche in the Italian population and to verify the influence of genetic, nutritional, and socioeconomic factors on menarcheal age. Recent studies suggest that the magnitude of the secular trend toward an earlier age at menarche is slackening in industrialized countries.MethodsThis multicenter study was conducted on a large, population-based sample of Italian high school girls (n = 3,783), using a self-administered questionnaire. The questionnaire was used to gather information on the girls, including demography, anthropometry, menarcheal date, regularity of menses, behavioral habits, and physical activity. The questionnaire was also used to gather information on parents, including demography and mothers' and sisters' menarcheal ages. The median age at menarche and its 95% confidence interval were estimated by means of Kaplan-Meier survival analysis. To identify the independent predictive factors of age at menarche, multivariate mixed-effects models were applied.ResultsThe median age at menarche of the subjects was 12.4 years (95% confidence interval: 12.34–12.46). The girls had their first menses approximately one-quarter of a year (median–0.13) earlier than did their mothers (p < .0001). Among all variables, parents' birth area, body mass index, family size, and the mother's menarcheal age were significantly and independently associated with age at menarche.ConclusionsThis study confirmed the reduction in the trend toward earlier menarche in Italy. The results also confirmed that genetic and nutritional factors are strong markers for early menarche. Currently, socioeconomic factors do not seem to play as significant a role as in the past.     

Antibiotic exposure by 6 months and asthma and allergy at 6 years: Findings in a cohort of 1,401 US children

Many studies have reported that antibiotic use may be associated with increased risk of childhood asthma. Respiratory tract infections in small children may be difficult to distinguish from early symptoms of asthma, and studies may have been confounded by "protopathic" bias, where antibiotics are used to treat early symptoms of asthma. These analyses of a cohort including 1,401 US children assess the association between antibiotic use within the first 6 months of life and asthma and allergy at 6 years of age between 2003 and 2007. Antibiotic exposure was associated with increased risk of asthma (adjusted odds ratio = 1.52, 95% confidence interval (CI): 1.07, 2.16). The odds ratio if asthma was first diagnosed after 3 years of age was 1.66 (95% CI: 0.99, 2.79) and, in children with no history of lower respiratory infection in the first year of life, the odds ratio was 1.66 (95% CI: 1.12, 3.46). The adverse effect of antibiotics was particularly strong in children with no family history of asthma (odds ratio = 1.89, 95% CI: 1.00, 3.58) (P(interaction) = 0.03). The odds ratio for a positive allergy blood or skin test was 1.59 (95% CI: 1.10, 2.28). The results show that early antibiotic use was associated with asthma and allergy at 6 years of age, and that protopathic bias was unlikely to account for the main findings.     

Reproductive characteristics and the age at inception of the perimenopause in a British National Cohort

Data from a British national cohort of women born in 1946 were used to investigate the hypothesis that the rate of depletion of oocyte numbers is associated with the age at which a woman reaches the inception of the perimenopause. Menopausal status was obtained using an annual questionnaire, sent to the cohort since the age of 47 years, and risk factor information from contacts with the survey throughout earlier life. Parous women entered the perimenopause later than nulliparous women. Those with the most children had the latest perimenopause, where the estimated hazard ratio for women having four or more children compared with those having none was 0.56 (95% confidence interval 0.39-0.81). Women who had a unilateral oophorectomy reached perimenopause earlier then those who had not (hazard ratio = 1.96, 95% confidence interval 1.15-3.35). There was some evidence that early age at menarche and short menstrual cycles were associated with an earlier perimenopause. No relation was observed with oral contraceptive pill use. Results provided some support for the hypothesis under consideration, while estimates of the median age at inception of the perimenopause due to these factors ranged from 46 to 50 years, which is an important variation with respect to later health.     

Management of cryptorchism and risk of testicular cancer

Cryptorchism is an established risk factor for testicular cancer, but the role of age at surgical correction is unclear. The authors investigated this relation using information obtained from comprehensive medical records dating to childhood. They conducted a case-control study of 183 Kaiser Permanente members, who were diagnosed with testicular cancer during 1973-1996 and who were 15 years or younger when they first joined the health plan, and 551 controls. Notes pertaining to the testes were reviewed up to the case's diagnosis date or comparable date among the controls. The odds ratio for the association of a history of cryptorchism with testicular cancer risk was 4.8 (95% confidence interval (CI): 1.9, 11.8). Compared with no history of cryptorchism, men with a history who had natural descent or successful orchiopexy by the 11th birthday were not at increased risk of testicular cancer (odds ratio = 0.6, 95% CI: 0.08, 5.4). However, successful treatment of cryptorchism only after the 11th birthday, or never, was related to a 32-fold increased risk (95% CI: 4, 250). Orchiopexy was performed before the 11th birthday on three men who developed testicular cancer but, in each, the procedure failed. In contrast, all four of the early orchiopexies performed on the controls were successful. Boys with failed orchiopexy should be considered for reoperative orchiopexy or orchiectomy to prevent testicular cancer.     

Low digit ratio predicts early age at menarche in colombian schoolgirls

Background: The ratio between the lengths of the second and fourth fingers (digit ratio: 2D : 4D), a purported negative correlate of prenatal androgen exposure, has been inversely related to age at menarche. However, a recent study found high digit ratios in carriers of a single variant in the LIN28B gene, which has been linked to delayed menarche. Methods: We investigated the association of digit ratio and age at menarche in 299 pre‐menarcheal girls aged 5–12 years who participated in a longitudinal cohort study in Bogotá, Colombia. Finger lengths were measured at baseline and the occurrence of menarche was periodically ascertained over a median 32 months of follow‐up. We used time‐to‐event analysis to estimate median ages at menarche as well as hazard ratios for menarche according to tertiles of the digit ratio for each hand. Results: Estimated median age at menarche was lower for girls in the lowest digit ratio tertile of the right hand compared with those in the highest (12.0 vs. 12.3 years; P‐value = 0.04). After adjustment for baseline age, height‐ and body mass index‐for‐age z‐scores, the hazard of menarche was 86% higher in girls of the lowest digit ratio tertile (hazard ratio 1.9 [95% confidence interval 1.2, 2.9]) compared with those in the highest digit ratio tertile of the right hand. No significant associations were found with the left hand. Conclusions: Digit ratio was positively associated with age at menarche in this longitudinal investigation, consistent with results from a recent gene‐linkage study.     

Prenatal and childhood environmental tobacco smoke exposure and age at menarche

Ferris JS, Flom JD, Tehranifar P, Mayne ST, Terry MB. Prenatal and childhood environmental tobacco smoke exposure and age at menarche. Paediatric and Perinatal Epidemiology 2010; 24: 515–523. Previous studies have reported mixed results regarding the association between age at menarche and environmental tobacco smoke exposure, both prenatally and during early childhood; however, few studies have had data available during both time periods. The present study examined whether exposure to prenatal tobacco smoke (PTS) via maternal smoking during pregnancy or childhood environmental tobacco smoke (ETS) was associated with age at menarche in a multi‐ethnic birth cohort. With the uniquely available prospectively collected data on body size and growth at birth and in early life, we further examined whether the association between PTS and ETS exposure and age at menarche was mediated by these variables. From 2001 to 2006, we recruited 262 women born between 1959 and 1963 who were enrolled previously in a New York City site of the National Collaborative Perinatal Project. Mothers who smoked during pregnancy vs. those who did not were more likely to be White, younger, have more education and have lower birthweight babies. Daughters with heavy PTS exposure (≥20 cigarettes per day) had a later age at menarche (>12 years vs. ≤12 years), odds ratio (OR) = 2.1 [95% confidence interval (CI) 0.9, 5.0] compared with daughters with no PTS. Daughters exposed to only childhood ETS had a later age at menarche, OR = 2.1 [95% CI 1.0, 4.3], and those exposed to PTS and ETS combined had a statistically significant later age at menarche, OR = 2.2 [95% CI 1.1, 4.6] compared with daughters with no PTS and no ETS. These results did not change after further adjustment for birthweight and postnatal growth suggesting that exposure to PTS and ETS is associated with later age at menarche even after considering possible relationships with growth.     

Joint associations between genetic variants and reproductive factors in glioma risk among women

In a pooled analysis of 4 US epidemiologic studies (1993-2001), the authors evaluated the role of 5 female reproductive factors in 357 women with glioma and 822 controls. The authors further evaluated the independent association between 5 implicated gene variants and glioma risk among the study population, as well as the joint associations of female reproductive factors (ages at menarche and menopause, menopausal status, use of oral contraceptives, and menopausal hormone therapy) and these gene variants on glioma risk. Risk estimates were calculated as odds ratios and 95% confidence intervals that were adjusted for age, race, and study. Three of the gene variants (rs4295627, a variant of CCDC26; rs4977756, a variant of CDKN2A and CDKN2B; and rs6010620, a variant of RTEL1) were statistically significantly associated with glioma risk in the present population. Compared with women who had an early age at menarche (<12 years of age), those who reported menarche at 12-13 years of age or at 14 years of age or older had a 1.7-fold higher risk and a 1.9-fold higher risk of glioma, respectively (P for trend = 0.009). Postmenopausal women and women who reported ever having used oral contraceptives had a decreased risk of glioma. The authors did not observe joint associations between these reproductive characteristics and the implicated glioma gene variants. These results require replication, but if confirmed, they would suggest that the gene variants that have previously been implicated in the development of glioma are unlikely to act through the same hormonal mechanisms in women.     

Hormone-related factors and risk of breast cancer in relation to estrogen receptor and progesterone receptor status

Risk factors were examined for subgroups of breast cancer characterized by estrogen receptor (ER) and progesterone receptor (PR) status. Data from the Carolina Breast Cancer Study, a population-based, North Carolina case-control study of 862 breast cancer cases aged 20-74 years diagnosed during 1993-1996 and 790 controls frequency matched on race and age, were obtained by personal interview. ER and PR status was retrieved from medical records (80%) or was determined in the authors' laboratory (11%) but was missing for 9% of cases. The receptor status distribution was as follows: 53% ER+PR+, 11% ER+PR-, 8% ER-PR+, and 28% ER-PR-. Several hormone-related factors were associated with stronger increased risks for ER+PR+ than for ER-PR- breast cancer: the elevated odds ratios were strongest for ER+PR+ breast cancer among postmenopausal women who had an early age at menarche (odds ratio (OR) = 1.6, 95% confidence interval (CI): 1.0, 2.4), nulliparity/late age at first full-term pregnancy (OR = 1.7, 95% CI: 0.9, 3.2 and OR = 1.6, 95% CI: 1.0, 2.7, respectively), or a high body mass index (OR = 1.6, 95% CI: 0.9, 3.0) and among pre-/perimenopausal women who had a high waist-hip ratio (OR = 1.9, 95% CI: 1.2, 3.1). In contrast, family history of breast or ovarian cancer and medical radiation exposure to the chest produced higher odds ratios for ER-PR- than for ER+PR+ breast cancer, especially among pre-/perimenopausal women.