Body fat distribution and obesity in pre- and postmenopausal breast cancer

BACKGROUND: Excessive body weight is known to increase the risk of postmenopausal, but not premenopausal breast cancer. Some studies have suggested that being overweight is protective against premenopausal breast cancer, but the evidence is not compelling. Much less is known about the role of body fat distribution in either pre- or postmenopausal breast cancer. METHODS: Breast cancer risk was examined in relation to body weight, height, Quetelet index (kg/m2), and waist/hip ratio (WHR) in the New York University Women's Health Study, a prospective cohort study. Cases were 109 premenopausal and 150 postmenopausal women diagnosed with breast cancer between 1985 and 1994. Non-cases were 8,157 cohort members free of breast cancer. RESULTS: Among premenopausal women, there was an increasing risk of breast cancer with increasing WHR. The relative risk (RR) of breast cancer increased to 1.72 (95% confidence interval [CI]: 1.0-3.1) in the upper quartile of WHR. The association was limited to subjects who had elevated Quetelet index, but not among those with lower weight. Overall, Quetelet index itself was not related to breast cancer risk in the premenopausal group, but there was a protective association among those ranking below the median WHR. In postmenopausal women, the RR for breast cancer increased to 2.36 (95% CI: 1.4-3.9) in the upper quartile of Quetelet index, but there was no association with WHR. Height was not associated with breast cancer in this study. CONCLUSIONS: The study confirms that excessive body weight increases breast cancer risk in postmenopausal women. On the contrary, in premenopausal women, excessive body weight may be protective among women who have a lower-body type of fat accumulation (low WHR). An upper-body fat accumulation (high WHR) is a predictor of breast cancer risk in premenopausal women, and this effect is especially pronounced among subjects who are overweight.     

Waist circumference, waist:hip ratio, and risk of breast cancer in the Nurses' Health Study

This study examined prospectively the associations of waist circumference and waist:hip circumference ratio with risk of breast cancer. A total of 47,382 US registered nurses who reported their waist and hip circumferences in 1986 were followed up through May 1994 for identification of incident cases of breast cancer. During 333,097 person-years of follow-up, 1,037 invasive breast cancers were diagnosed. In proportional hazards analyses, waist circumference was nonsignificantly related to risk of premenopausal breast cancer but was significantly associated with postmenopausal breast cancer after adjustment for established breast cancer risk factors (for the highest quintile of waist circumference vs. the lowest, relative risk (RR) = 1.34; 95% confidence interval (CI): 1.05, 1.72). When the analysis was limited to postmenopausal women who had never received hormone replacement therapy, a stronger positive association was found (RR = 1.88; 95% CI: 1.25, 2.85). After the data were further controlled for body mass index, the positive association was only slightly attenuated (RR = 1.83; 95% CI: 1.12, 2.99). Among past and current postmenopausal hormone users, no significant associations were found. Similar but slightly weaker associations were observed between waist:hip ratio and breast cancer risk. These data suggest that greater waist circumference increases risk of breast cancer, especially among postmenopausal women who are otherwise at lower risk because of never having used estrogen replacement hormones.     

Association of body composition and weight history with breast cancer prognostic markers: divergent pattern for Hispanic and non-Hispanic White women

Body composition and weight gain are breast cancer risk factors that may influence prognosis. The Health, Eating, Activity, and Lifestyle Study was designed to evaluate the relations of body composition, weight history, hormones, and lifestyle factors to prognosis for women with breast cancer. In the cross-sectional analysis of this cohort study specific to 150 Hispanic and 466 non-Hispanic White women in New Mexico diagnosed between 1996 and 1999, the authors hypothesized that obesity measures are associated with baseline prognostic markers and that these associations are modified by ethnicity. Ethnic-stratified multiple logistic regression analyses showed divergent results for a tumor size of 1.0 cm or more and, to a lesser extent, positive lymph node status. Among Hispanics, the highest quartile for body mass index (29.5 vs. <22.5 kg/m2: odds ratio (OR) = 0.16, 95% confidence interval (CI): 0.03, 0.84) and for waist circumference (> or =95.0 vs. <78.5 cm: OR = 0.09, 95% CI: 0.01, 0.78) was significantly associated with a reduced tumor size. In contrast, for overweight and obese non-Hispanic White women, there was an increased association with obesity-related measures, particularly striking for the highest quartile of waist circumference (OR = 2.76, 95% CI: 1.45, 5.26). These findings suggest that Hispanics may have a different breast cancer phenotype than non-Hispanic Whites, which associates differently with body composition and weight history.     

Race, anthropometric factors, and stage at diagnosis of breast cancer

A recent study suggested that the greater prevalence of severe obesity among African-American women explained almost one third of the observed differences between African-American and White women in stage at diagnosis of breast cancer. The objective of this investigation was to attempt to replicate these findings in a second, larger population and to expand the analyses by including a measure of body fat distribution, the waist:hip ratio. The authors used data from a population-based study in North Carolina comprising 791 breast cancer cases (302 in African-American women and 489 in White women) diagnosed between 1993 and 1996. African-American women were more likely to have later-stage (TNM stage >/=II) breast cancer (odds ratio (OR) = 2.2; 95% confidence interval (CI): 1.6, 2.9). They also were much more likely to be severely obese (body mass index >/=32.3) (OR = 9.7; 95% CI: 6.5, 14.5) and to be in the highest tertile of waist:hip ratio (OR = 5.7; 95% CI: 3.8, 8.6). In multivariate logistic regression models, adjustment for waist:hip ratio reduced the odds ratio for later-stage disease in African-American women by 20%; adjustment for both waist:hip ratio and severe obesity reduced the odds ratio by 27%. These observations suggest that obesity and body fat distribution, in addition to socioeconomic and medical care factors, contribute to racial differences in stage at breast cancer diagnosis.     

Physical activity and breast cancer risk in hispanic and non-hispanic white women

To investigate breast cancer risk in Hispanic and non-Hispanic White women, the authors conducted a population-based case-control study of New Mexican women during 1992-1994 using incident breast cancer cases aged 35-74 years and frequency-matched controls selected using random digit dialing. Activity type and weekly duration of usual nonoccupational physical activity were used to calculate weekly metabolic equivalent (MET)-hours of total and vigorous physical activity (> or =5 METs). Conditional logistic regression models were fitted to estimate the relative risk of breast cancer for levels of physical activity and to assess the difference in effects by ethnicity, body mass index, energy intake, and menopausal status. Vigorous physical activity was associated with reduced breast cancer risk in both Hispanic and non-Hispanic White women. Women in the highest category of vigorous activity had lower risk of breast cancer (adjusted odds ratio = 0.34, 95% confidence interval: 0.22, 0.51 for Hispanic; adjusted odds ratio = 0.60, 95% confidence interval: 0.41, 0.89 for non-Hispanic White women) compared with women reporting no vigorous physical activity. Both pre- and postmenopausal Hispanic women showed decreasing risk with increasing level of activity. Physical activity was protective only among postmenopausal non-Hispanic White women. The effects of physical activity were independent from reproductive factors, usual body mass index, body mass index at age 18, adult weight gain, and total energy intake.     

Effect of adiposity and fat distribution on endometrial cancer risk in Shanghai women

The authors conducted a population-based case-control study of 832 endometrial cancer cases and 846 frequency-matched controls in Shanghai, China (1997-2001), to examine the association of overall adiposity and body fat distribution with disease risk. Overall adiposity was estimated using weight and body mass index (BMI); upper body fat distribution was evaluated using waist circumference and waist:hip ratio. Overall and upper-body obesity were both associated with an elevated risk of endometrial cancer. Adjusted odds ratios and 95% confidence intervals for highest-versus-lowest quartile comparisons were 2.6 (95% confidence interval (CI): 2.0, 3.5) for weight, 2.9 (95% CI: 2.2, 3.9) for BMI, 4.7 (95% CI: 3.4, 6.4) for waist circumference, and 3.5 (95% CI: 2.6, 4.8) for waist:hip ratio. The positive associations with weight and BMI vanished after results were controlled for waist circumference, while associations with waist circumference and waist:hip ratio persisted after adjustment for BMI. The positive association with upper-body obesity was more pronounced among younger women, women who had never used oral contraceptives, and women with a history of diabetes mellitus (p for multiplicative interaction < 0.05). Upper-body obesity was related to increased risk among women with low BMI. These results suggest that obesity, particularly upper-body fat deposition, is associated with an increased risk of endometrial cancer.     

Risk factors for fatal breast cancer in African-American women and White women in a large US prospective cohort

African-American women have a higher lifetime risk of fatal breast cancer than do White women. Recent studies suggest that breast cancer risk factors may vary by race. The authors examined risk factors for fatal breast cancer in postmenopausal African-American women and White women in a large US prospective cohort. In 1982, 21,143 African-American women and 409,093 White women in the Cancer Prevention Study II completed a questionnaire on reproductive, medical, anthropometric, and demographic factors. During a 20-year follow-up, 257 deaths from breast cancer occurred among African-American women and 4,265 among Whites. Cox proportional hazards modeling was used to calculate multivariate-adjusted rate ratios, stratified by race. Higher body mass index, taller height, and physical inactivity were associated with increased breast cancer mortality rates in both groups. A college education was associated with higher mortality from breast cancer only in Africa-American women (hazard ratio = 1.62, 95% confidence interval: 1.13, 2.30; p(trend) = 0.01, vs. less than a high school education). Most other risk factors were associated with breast cancer rates similarly in both groups. With few exceptions, established breast cancer risk factors were similarly associated with risk of death from breast cancer among African-American women and White women.     

Relation between obesity and breast cancer in young women

This study was conducted to assess the relation between body size and risk of breast cancer among young women. A case-control study was conducted among women aged 21-45 years living in three counties in Washington State. Cases were women born after 1944 with invasive or in situ breast cancer that was diagnosed between January 1, 1983, and April 30, 1990. Controls were selected using random digit dialing and were frequency-matched to cases on the basis of age and county of residence. Interviews took place between 1986 and 1992. Body size was evaluated using indices from several different time periods. After adjustment for confounders, a decreased risk of breast cancer was found for women in the highest quintile of body mass index (weight (kg)/height (m)2) as compared with the lowest quintile (for maximum lifetime body mass index, odds ratio = 0.69, 95% confidence interval (CI) 0.51-0.94). Age modified the relation between body size and risk of breast cancer. The odds ratio for women in the highest quintile of maximum body mass index who were aged 21-35 years was 0.29 (95% CI 0.16-0.55), as compared with an odds ratio of 1.5 for women aged 36-45 years (95% CI 0.9-2.5) (p for interaction = 0.003). This study supports prior research showing a decreased risk of breast cancer associated with increased body size among premenopausal or young women. More detailed analysis in this study found a strong effect that was limited to the youngest age group (< or = 35 years).     

身体测量指标与女性乳腺癌关系的前瞻性队列研究

目的研究上海女性身体测量指标与绝经前后乳腺癌之间的关系.方法采用前瞻性队列研究方法.1997-2000年在上海市区建立一个73 461人年龄40～70岁的女性队列.每2年随访一次,至2004年6月共收集乳腺癌新发病例432例.用Cox回归模型估计身体测量指标与女性乳腺癌发生的相对危险度（RR）和95%可信区间（CI）.结果调整年龄、文化程度、能量摄入、月经、生育等混杂因素后,基线调查时体重、体重指数（BMI）、腰臀围比例（WHR）和20岁后体重增加与绝经后女性乳腺癌危险性呈正相关,与绝经前女性乳腺癌发生无关.身高与乳腺癌危险的显著正相关关系仅在绝经前女性中发现,20岁时身高在161 cm以上者发生乳腺癌的危险是157.1 cm以下者的1.84倍（95%CI：1.30～2.61）.20岁时BMI处于平均水平者绝经前患乳腺癌的危险性显著高于其他两组.BMI和WHR互相调整后,WHR独立于BMI的作用接近显著性水平.调整BMI后,20岁后体重增加会显著增加绝经后乳腺癌危险（RR=1.61,95%CI：1.09～2.37）.结论对于绝经后女性,成年后体重增加和中心性肥胖都是预测乳腺癌危险的指标.因此控制成年后体重、减少腹部脂肪堆积是预防绝经后乳腺癌发生的有效措施.身高可能是影响绝经前女性乳腺癌发生的危险因素.     

Anthropometric variables in relation to risk of breast cancer in middle-aged women

BACKGROUND: Many epidemiological studies have assessed the relationships between anthropometric variables and breast cancer risk. However, methodological approaches for analysing these factors differ appreciably. Also, age when maximum height is achieved has been identified as a potential risk factor for breast cancer in premenopausal women, but this issue has not been studied in postmenopausal women. METHODS: The participants in this population-based case-control study were postmenopausal women 50-64 years of age from the general female population of western Washington State. It included 479 women with incident primary breast cancer and 435 controls. RESULTS: This study found that: (i) women who gained over 70 pounds since age 18 had an increased risk of breast cancer relative to those who stayed within 10 pounds of their weight at age 18 (odds ratio [OR] = 2.7; 95% CI: 1.5-4.9), (ii) women with body mass indices (BMI) below what is considered healthy had a decreased risk (OR = 0.4; 95% CI: 0.2-1.1) while women with a BMI in the obese range had an increased risk of breast cancer (OR = 1.4; 95% CI: 1.0-2.1), and (iii) women who reached their maximum height at or after the age of 18 had a decreased risk of breast cancer compared to women who reached their maximum height at age 13 or younger (OR = 0.7; 95% CI: 0.5-1.0). CONCLUSIONS: By examining various anthropometric variables using clinically relevant strata, a clearer picture of how these variables relate to postmenopausal breast cancer risk was developed. Similar to younger women, postmenopausal women who reached their maximum height at later ages had a decreased risk of breast cancer.     

Physical activity and breast cancer risk among women in the southwestern United States

Physical activity may influence breast cancer risk through multiple mechanisms and at different periods in life. In this study we evaluate breast cancer risk associated with total and vigorous physical activity at ages 15, 30, and 50 years and the referent year prior to diagnosis/selection. Participants were non-Hispanic white (NHW) (1527 cases and 1601 control subjects) and Hispanic/American Indian (HAI) (798 cases and 924 controls) women. Both total and vigorous activity reduced risk of breast cancer in a dose-response manner. Among premenopausal women, only high total metabolic equivalent of the task (MET) hours of activity during the referent year was associated with reduced breast cancer risk in NHW women (odds ratio [OR] 0.62; 95% confidence interval [CI] 0.43, 0.91). Among postmenopausal women, physical activity had the greatest influence among women not recently exposed to hormones. Among these women, high total lifetime activity reduced risk of breast cancer for both NHW (OR 0.60; 95% CI 0.36, 1.02; p trend 0.01) and HAI women (OR 0.52; 95% CI 0.23, 1.16; p trend 0.07). Additionally, high total MET hours of activity at age 30 years (OR 0.56; 95% CI 0.37, 0.85) and at age 15 years (OR 0.57; 95% CI 0.38, 0.88) reduced breast cancer risk among postmenopausal NHW women not recently exposed to hormones. Among HAI women, more recent activity performed during the referent year and at age 50 appeared to have the greatest influence on breast cancer risk. Among postmenopausal NHW women. there was a significant interaction between physical activity and hormone replacement therapy (p value, 0.01), while among postmenopausal HAI women, physical activity interacted with body mass index (p value, 0.04). These data suggest that physical activity is important in reducing risk of breast cancer in both NHW and HAI women.     

Pooled analysis of prospective cohort studies on height, weight, and breast cancer risk

The association between anthropometric indices and the risk of breast cancer was analyzed using pooled data from seven prospective cohort studies. Together, these cohorts comprise 337,819 women and 4,385 incident invasive breast cancer cases. In multivariate analyses controlling for reproductive, dietary, and other risk factors, the pooled relative risk (RR) of breast cancer per height increment of 5 cm was 1.02 (95% confidence interval (CI): 0.96, 1.10) in premenopausal women and 1.07 (95% CI: 1.03, 1.12) in postmenopausal women. Body mass index (BMI) showed significant inverse and positive associations with breast cancer among pre- and postmenopausal women, respectively; these associations were nonlinear. Compared with premenopausal women with a BMI of less than 21 kg/m2, women with a BMI exceeding 31 kg/m2 had an RR of 0.54 (95% CI: 0.34, 0.85). In postmenopausal women, the RRs did not increase further when BMI exceeded 28 kg/m2; the RR for these women was 1.26 (95% CI: 1.09, 1.46). The authors found little evidence for interaction with other breast cancer risk factors. Their data indicate that height is an independent risk factor for postmenopausal breast cancer; in premenopausal women, this relation is less clear. The association between BMI and breast cancer varies by menopausal status. Weight control may reduce the risk among postmenopausal women.     

Body Weight,Central Adiposity,and Fasting Hyperglycemia Are Associated with Tumor Characteristics in a Brazilian Cohort of Women with Breast Cancer

The aim of this study was to evaluate the association of overweight, obesity, excess central adiposity, hyperglycemia, and diabetes mellitus with tumor characteristics in breast cancer. In this retrospective cohort study that enrolled 2127 women with breast cancer, the independent variables collected were fasting blood glucose, body mass index, central adiposity (waist circumference and waist-to-hip circumference ratio (WHR)), and waist-to-height ratio. The tumor characteristics (infiltrating, ductal grade, hormone receptor-positive (HR+), human epidermal growth factor receptor, triple negative, size, lymph node involvement, and clinical stage) were the dependent variables. Most of the women were postmenopausal (73.5%), with an infiltrating tumor (83.0%), HR+ (82.0%), and overweight or obese (71.0%). For the premenopausal women, obesity was associated with grade 3 ductal tumor (odds ratio (OR): 1.70; 95% confidence interval (95% CI): 1.09–2.66), triple negative (OR: 1.37, 95% CI: 1.08–3.24), and size ≥ 2 cm (OR: 2.20, 95% CI: 1.36–3.56). For the postmenopausal women, obesity was associated with WHR, infiltrating tumor (OR: 1.73, 95% CI: 1.56–1.95), size ≥ 2 cm (OR: 1.38, 95% CI: 1.11–1.71), lymph node involvement (OR: 1.24, 95% CI: 1.02–1.56), and stages III–IV (OR: 1.76, 95% CI: 1.30–2.65). Excess body weight and central adiposity were associated with tumor aggressiveness characteristics in women with breast cancer, confirming the importance of nutritional status.     

Variation in mammographic breast density by race

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

Risk factors for breast cancer in elderly women

As the population ages, an increasing fraction of women diagnosed with breast cancer will be elderly. Heterogeneity of breast cancer risk factors between pre- and postmenopausal women is recognized, but few studies have examined elderly women specifically. The authors describe the age-specific influence of risk factors for postmenopausal breast cancer, with emphasis on women aged 75 or more years. Among 36,658 members of the Iowa Women's Health Study (1986-2001), a population-based cohort study, 428 incident breast cancers were diagnosed in women aged 55-64 years, 1,297 in women aged 65-74 years, and 561 in women aged 75-84 years. Women with a body mass index (weight (kg)/height (m)(2)) in the highest versus the lowest quartile were at increased risk of breast cancer at age 75 or more years (adjusted hazard ratio = 1.44, 95% confidence interval (CI): 1.12, 1.84). Family history of breast cancer (hazard ratio = 1.54, 95% CI: 1.24, 1.93 for a first-degree family history vs. none) and an older age at menopause (p(trend) = 0.07) conferred increased risk for women aged 75 or more years, and a high number of livebirths was protective (hazard ratio = 0.67, 95% CI: 0.51, 0.88 for five or more births compared with one or two). Obesity, a modifiable risk factor, remained positively associated with breast cancer for all age groups of postmenopausal women.     

Interaction of waist/hip ratio and family history on the risk of hormone receptor-defined breast cancer in a prospective study of postmenopausal women

The authors previously reported an interaction of waist/hip ratio and family history on the risk of breast cancer in the Iowa Women's Health Study. Here they reexamine this association based on 9 additional years of follow-up, stratifying on tumor receptors for estrogen and progesterone. Data on risk factors and family history of breast cancer were ascertained in 1986. The occurrences of breast cancer and estrogen receptor/progesterone receptor were determined through the Iowa Surveillance, Epidemiology, and End Results' registry. Rate ratios were elevated with increasing weight and body mass index and decreasing body mass index at age 18 years, but they did not vary by family history. There was no association with height, waist circumference, or waist/hip ratio. A linear trend of increasing risk with increasing waist/hip ratio was observed among family history-positive women (p = 0.06) but not among family history-negative women (p = 0.87). This apparent interaction (p = 0.09) was examined by estrogen receptor or progesterone receptor status. When stratified on family history and estrogen receptor, no clear patterns were evident. In contrast, family history-positive women in the upper quintile of the waist/hip ratio were at 2.2-fold greater risk of progesterone receptor-negative tumors compared with those in the lowest quintile (95% confidence interval: 0.9, 5.8). Thus, the previously reported interaction between family history and waist/hip ratio is still (weakly) evident and appears to reflect risk for progesterone receptor-negative tumors.     

Adult body size, hormone receptor status, and premenopausal breast cancer risk in a multiethnic population: the San Francisco Bay Area breast cancer study

Large body size has been associated with a reduced risk of premenopausal breast cancer in non-Hispanic white women. Data on other racial/ethnic populations are limited. The authors examined the association between premenopausal breast cancer risk and adult body size in 672 cases and 808 controls aged ≥35 years from a population-based case-control study conducted in 1995-2004 in the San Francisco Bay Area (Hispanics: 375 cases, 483 controls; African Americans: 154 cases, 160 controls; non-Hispanic whites: 143 cases, 165 controls). Multivariate adjusted odds ratios and 95% confidence intervals were calculated using unconditional logistic regression. Height was associated with increased breast cancer risk (highest vs. lowest quartile: odds ratio = 1.77, 95% confidence interval: 1.23, 2.53; P(trend) < 0.01); the association did not vary by hormone receptor status or race/ethnicity. Body mass index (measured as weight (kg) divided by height (m) squared) was inversely associated with risk in all 3 racial/ethnic groups, but only for estrogen receptor- and progesterone receptor-positive tumors (body mass index ≥30 vs. <25: odds ratio = 0.42; 95% confidence interval: 0.29, 0.61). Other body size measures (current weight, body build, adult weight gain, young adult weight and body mass index, waist circumference, and waist-to-height ratio) were similarly inversely associated with risk of estrogen receptor- and progesterone receptor-positive breast cancer but not estrogen receptor- and progesterone receptor-negative disease. Despite racial/ethnic differences in body size, inverse associations were similar across the 3 racial/ethnic groups when stratified by hormone receptor status.     

Interaction between smoking and obesity and the risk of developing breast cancer among postmenopausal women: the Women's Health Initiative Observational Study

Obesity is a well-established risk factor for postmenopausal breast cancer. Recent studies suggest that smoking increases the risk of breast cancer. However, the effect of co-occurrence of smoking and obesity on breast cancer risk remains unclear. A total of 76,628 women aged 50-79 years enrolled in the Women's Health Initiative Observational Study were followed through August 14, 2009. Cox proportional hazards regression models were used to estimate hazard ratios and 95% confidence intervals. Over an average 10.3 years of follow-up, 3,378 incident cases of invasive breast cancer were identified. The effect of smoking on the risk of developing invasive breast cancer was modified significantly by obesity status among postmenopausal women, regardless of whether the obesity status was defined by body mass index (P(interaction) = 0.01) or waist circumference (P(interaction) = 0.02). A significant association between smoking and breast cancer risk was noted in nonobese women (hazard ratio = 1.25, 95% confidence interval: 1.05, 1.47) but not in obese women (hazard ratio = 0.96, 95% confidence interval: 0.69, 1.34). In conclusion, this study suggests that the effect of smoking exposure on breast cancer risk was modified by obesity among postmenopausal women. The modification effect did not differ by general versus abdominal obesity.     

Body size across the life course, mammographic density, and risk of breast cancer

Adult body mass index (BMI) is inversely associated with premenopausal breast cancer risk, and childhood and adolescent body size is inversely associated with breast cancer risk in pre- and postmenopausal women. Breast density is inversely related to body size and may play a role in the association of body size with breast cancer risk. The authors conducted a nested case-control study including 1,528 cases and 2,844 controls from the Nurses' Health Study (1989-2004) and Nurses' Health Study II (1996-2003). Prior to breast cancer diagnosis, participants reported their body fatness during childhood and adolescence, BMI at age 18 years, and current BMI. Mammographic density was measured by using a computer-assisted thresholding method. The inverse association between adult BMI and premenopausal breast cancer (for BMI ≥30 vs. BMI 20-22.4, odds ratio = 0.64, 95% confidence interval: 0.38, 1.06) (P(trend) = 0.36) became positive after adjustment for mammographic density (odds ratio = 1.28, 95% confidence interval: 0.72, 2.30) (P(trend) = 0.07). Conversely, the inverse association between childhood and adolescent body size and breast cancer risk remained after adjustment for mammographic density. The inverse association between adult BMI and premenopausal breast cancer risk may be partially due to negative confounding by mammographic density. Conversely, mammographic density does not appear to explain the inverse association between childhood and adolescent body fatness and breast cancer risk.     

Menstrual history and risk of hip fractures in postmenopausal women. The Iowa Women's Health Study

The authors examined prospectively between 1986 and 1997 the relation of irregular menstrual cycles and irregular menstrual bleeding duration earlier in life with risk of hip fracture in 33,434 postmenopausal Iowa women. Over the 318,522 person-years of follow-up, 523 hip fractures were reported. Adjusted for age, smoking, body mass index, waist/hip ratio, and estrogen use, the relative risk of hip fracture in women who reported always having irregular menstrual cycles, compared with women who never had irregular cycles, was 1.36 (95% confidence interval (CI): 1.03, 1.78). Women who reported having irregular menstrual bleeding duration had a 1.40-fold (95% CI: 1.10, 1.78) increased risk of hip fracture compared with women with regular bleeding duration. In addition, women who reported having both irregular menstrual cycles and irregular menstrual bleeding had a 1.82-fold (95% CI: 1.55, 2.15) higher risk of hip fracture than did women who reported neither irregularity. Women who reported only one menstrual disturbance did not have a risk of hip fracture that was significantly different from women who reported no menstrual disturbances. The authors conclude that women with menstrual irregularities are at increased risk of hip fracture, probably because they are estrogen or progesterone deficient.