Body size in early life and adult levels of insulin-like growth factor 1 and insulin-like growth factor binding protein 3

Body size in early life has been associated with breast cancer risk. This may be partly mediated through the insulin-like growth factor (IGF) pathway. The authors assessed whether birth weight, body fatness at ages 5 and 10 years, and body mass index (BMI; weight (kg)/height (m)(2)) at age 18 years were associated with plasma concentrations of insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 3 in 6,520 women aged 32-70 years at blood draw from the Nurses' Health Study (1990-2006) and Nurses' Health Study II (1997-2005). Birth weight, body fatness in childhood, and BMI at age 18 years were inversely associated with adult IGF-1 levels. For example, IGF-1 levels were 11.9% lower in women who reported being heaviest at age 10 years than in those who were leanest at age 10 (P-trend < 0.0001). Further, women who reported their birth weight as ≥10 pounds (≥4.5 kg) (vs. <5.5 pounds (<2.5 kg)) had 7.9% lower IGF-1 levels (P-trend = 0.002). Women whose BMI at age 18 years was ≥30 (vs. <20) had 14.1% lower IGF-1 levels (P-trend < 0.0001). Similar inverse associations were observed for insulin-like growth factor binding protein 3. These observations did not vary by adult BMI or menopausal status at blood draw. These findings suggest that altered IGF-1 levels in adulthood may be a mechanism through which early-life body size influences subsequent breast cancer risk.     

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.     

Association of childhood and adolescent anthropometric factors, physical activity, and diet with adult mammographic breast density

Early-life exposures may influence the development of breast cancer. The authors examined the association of childhood and adolescent anthropometric factors, physical activity levels, and diet with adult mammographic breast density, a strong risk factor for breast cancer. Women in the Minnesota Breast Cancer Family Study cohort who had undergone mammograms but had not had breast cancer (n=1,893) formed the sample. Information on adolescent exposures, including relative height, weight, and physical activity at ages 7, 12, and 18 years and diet at age 12-13 years, was self-reported during two follow-up studies (1990-2003). Mammographic percent density was estimated using a computer-assisted thresholding program. Statistical analyses were performed using linear mixed-effects models with two-sided tests. Positive associations with height at ages 7 (p<0.001), 12 (p<0.001), and 18 (p<0.001) years and percent density were evident overall and within menopausal status categories. The minimum difference in percent density between the tallest and shortest girls was 3 percent, with a maximum of 7 percent. Weight at age 12 years (p=0.005) and adiposity at age 12 years (p=0.005) were both inversely associated with adult percent density. Adolescent physical activity and diet were unrelated to percent density. These results suggest that adolescent height, a known risk factor for breast cancer, is also associated with mammographic percent density.     

High-density lipoprotein cholesterol, obesity, and mammographic density in Korean women: the Healthy Twin study

Background

High-density lipoprotein cholesterol (HDL-C) is reported to be associated with breast cancer risk. To better understand this association, we examined the relationship between HDL-C and mammographic density, a putative intermediate risk factor for breast cancer.

Methods

The study subjects were 711 Korean women from the Healthy Twin study. Lipid parameters were assayed enzymatically in fresh sera, and percent dense area (PDA) and absolute dense area were measured from digital mammograms using a computer-assisted method.

Results

PDA was positively associated with HDL-C in both premenopausal and postmenopausal women in a multivariable-adjusted linear mixed model, but the association did not persist when the model was additionally adjusted for body mass index (BMI). BMI was inversely associated with PDA, and this association did not change after additional adjustment for any lipid parameter. Multivariable-adjusted analysis showed that there were significant additive genetic cross-trait correlations between PDA and both HDL-C (coefficient, 0.175) and triglyceride (coefficient, −0.262). However, those correlations disappeared after additional adjustment for BMI.

Conclusions

HDL-C alone is unlikely to increase the risk of breast cancer in Korean women, particularly through changes in breast parenchyma that are apparent in mammographic density. BMI should be included in studies using analytical models where mammographic density is used as an intermediate risk factor for breast cancer.Key words: breast cancer, high-density lipoprotein cholesterol, mammography, obesity     

Physical activity and mammographic breast density in the EPIC-Norfolk cohort study

Physical inactivity and high mammographic breast density have both been associated with increased breast cancer risk. However, the association between physical activity and mammographic breast density remains inconsistent. In the European Prospective Investigation of Cancer (EPIC)-Norfolk population-based cohort study (United Kingdom), the authors investigated the cross-sectional association between physical activity level at baseline during 1993-1997 and breast density among 1,394 postmenopausal, cancer-free women. Usual physical activity was assessed by a brief, validated questionnaire. Percentage breast density was determined visually from mammograms by three trained radiologists using the Boyd six-category scale. The association between physical activity level and breast density risk category was examined. No statistically significant association between physical activity and percentage breast density was observed in the unadjusted or adjusted regression models. A suggested increase in breast density for the most active women in the unadjusted regression analysis (odds ratio = 1.13, 95% confidence interval: 0.71, 1.80) was reversed after inclusion of body mass index and reproductive and lifestyle variables (odds ratio = 0.78, 95% confidence interval: 0.45, 1.34). The lack of an association between physical activity and percentage breast density suggests that an association between physical activity and breast cancer risk is unlikely to be mediated through an effect on mammographic breast density.     

Being breastfed in infancy and breast cancer incidence in adult life: results from the two nurses' health studies

Events during perinatal and early life may influence the incidence of breast cancer in adult life, and some case-control studies suggest that having been breastfed may reduce breast cancer risk. The authors studied this association among premenopausal and postmenopausal women by using data from the two Nurses' Health Studies, the Nurses' Health Study (using data from 1992 to 1996) and the Nurses' Health Study II (using data from 1991 to 1997). A history of being breastfed was self-reported by the study participants. During a total of 695,655 person-years, 1,073 cases of invasive breast cancer were diagnosed. The authors did not observe any important overall association between having been breastfed and the development of breast cancer later in life among premenopausal women (covariate-adjusted relative risk = 0.97, 95% confidence interval (CI): 0.78, 1.20) or postmenopausal women (covariate-adjusted relative risk = 1.12, 95% CI: 0.92, 1.37). No significant trend was observed with increasing duration of breastfeeding. The authors also used data on breastfeeding retrospectively collected from 2,103 mothers of participants of the two Nurses' Health Studies. With the mothers' reports, the covariate-adjusted odds ratio of breast cancer was 1.11 (95% CI: 0.88, 1.39) for women who were breastfed compared with those who were not. Data from these two large cohorts do not support the hypothesis that being breastfed confers protection against subsequent breast cancer.     

The association between mammographic breast density and bone mineral density in the study of women's health across the nation

BACKGROUND: Bone mineral density and mammographic breast density are each associated with markers of lifetime estrogen exposure. The association between mammographic breast density and bone mineral density in early perimenopausal women is unknown. METHODS: We analyzed data from a cohort (n = 501) of premenopausal (no change in menstrual regularity) and early perimenopausal (decreased menstrual regularity in past 3 months) participants of African-American, Caucasian, Chinese, and Japanese ethnicity in the Study of Women's Health Across the Nation. Using multivariable linear regression, we examined the cross-sectional association between percent mammographic density and bone mineral density (BMD). RESULTS: Percent mammographic density was statistically significantly inversely associated with hip BMD and lumbar spine BMD after adjustment (body mass index, ethnicity, age, study site, parity, alcohol intake, cigarette smoking, physical activity, age at first childbirth) in early perimenopausal, but not premenopausal, women. In early perimenopausal women, every 0.1g/cm(2) greater hip BMD predicted a 2% lower percent mammographic density (95% confidence interval -37.0 to -0.6%, p = 0.04). CONCLUSION: Mammographic breast density is inversely associated with BMD in the perimenopausal participants of this community-based cohort. The biological underpinnings of these findings may reflect differential responsiveness of breast and bone mineral density to the steroid milieu.     

Plasma carotenoids, retinol, and tocopherols and risk of breast cancer

The roles of carotenoids, retinol, and tocopherols in breast cancer etiology have been inconclusive. The authors prospectively assessed the relations between plasma alpha-carotene, beta-carotene, beta-cryptoxanthin, lycopene, lutein/zeaxanthin, retinol, alpha-tocopherol, and gamma-tocopherol and breast cancer risk by conducting a nested case-control study using plasma collected from women enrolled in the Nurses' Health Study. A total of 969 cases of breast cancer diagnosed after blood draw and prior to June 1, 1998, were individually matched to controls. The multivariate risk of breast cancer was 25-35% less for women with the highest quintile compared with that for women with the lowest quintile of alpha-carotene (odds ratio (OR) = 0.64, 95% confidence interval (CI): 0.47, 0.88; p(trend) = 0.01), beta-carotene (OR = 0.73, 95% CI: 0.53, 1.02; p(trend) = 0.01), lutein/zeaxanthin (OR = 0.74, 95% CI: 0.55, 1.01; p(trend) = 0.04), and total carotenoids (OR = 0.76, 95% CI: 0.55, 1.05; p(trend) = 0.05). The inverse association observed with alpha-carotene and breast cancer was greater for invasive cancers with nodal metastasis. The authors conclude that some carotenoids are inversely associated with breast cancer. Although the association was strongest for alpha-carotene, the high degree of collinearity among plasma carotenoids limits our ability to conclude that this association is specific to any individual carotenoid.     

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.     

Genetic variability in IGF-1 and IGFBP-3 and body size in early life

ABSTRACT: BACKGROUND: Early life body size and circulating levels of IGF-1 and IGFBP-3 have been linked to increased risks of breast and other cancers, but it is unclear whether these exposures act through a common mechanism. Previous studies have examined the role of IGF-1 and IGFBP-3 genetic variation in relation to adult height and body size, but few studies have examined associations with birthweight and childhood size. METHODS: We examined whether htSNPs in IGF-1 and the IGFBP-1/IGFBP-3 gene region are associated with the self-reported outcomes of birthweight, body fatness at ages 5 and 10, and body mass index (BMI) at age 18 among healthy women from the Nurses' Health Study (NHS) and NHSII. We used ordinal logistic regression to model odds ratios (ORs) and 95% confidence intervals (CI) of a one category increase for birthweight and somatotypes at ages 5 and 10. We used linear regression to model associations with BMI at age 18. RESULTS: Among 4567 healthy women in NHS and NHSII, we observed no association between common IGF-1 or IGFBP-1/IGFBP-3 SNPs and birthweight, body fatness at ages 5 and 10, or BMI at age 18. CONCLUSIONS: Common IGF-1 and IGFBP-1/IGFBP-3 SNPs are not associated with body size in early life.     

Body size and breast cancer risk in black women and white women: the Carolina Breast Cancer Study

The relation between body size and breast cancer risk was investigated in a population-based, case-control study of Black women (350 cases, 353 controls) and White women (523 cases, 471 controls) from North Carolina, aged 20-74 years in 1993-1996. Logistic regression analyses compared tertiles of each body size variable, adjusting for age and breast cancer risk factors (results shown for highest relative to lowest tertile). Among premenopausal women, body mass index (kg/m2) was inversely associated with breast cancer (odds ratio (OR) = 0.46, 95% confidence interval (CI): 0.26, 0.80) for Whites but not for Blacks. There was essentially no association among postmenopausal women. Higher waist/hip ratio, adjusted for body mass index, increased risk for all women. Odds ratios for Black and White premenopausal women were 2.50 (95% CI: 1.10, 5.67) and 2.44 (95% CI: 1.17, 5.09), respectively; odds ratios for Black and White postmenopausal women were 1.62 (95% CI: 0.70, 3.79) and 1.64 (95% CI: 0.88, 3.07), respectively. Findings for body mass index differed among Black women when stratified by age (<50 years) (OR = 0.50, 95% CI: 0.25, 1.01) instead of menopausal status. Thus, the associations of breast cancer with body mass index and waist/hip ratio among Black women are similar to those documented for Whites, despite different body size profiles on average.     

Intervention with a low-fat, high-carbohydrate diet does not influence the timing of menopause

BACKGROUND: Later age at menopause is associated with a greater risk of breast cancer. Dietary factors may at least partially influence breast cancer risk through an effect on the age at menopause. OBJECTIVE: We studied the effect of a low-fat, high-carbohydrate (LFHC) dietary intervention on the timing of menopause in women with greater risk of breast cancer. DESIGN: The study population included participants from an LFHC dietary intervention trial for the prevention of breast cancer in women with extensive mammographic density, a strong risk factor for breast cancer. Women who were premenopausal at baseline (n = 2611) were followed for an average of 7 y for menopause. Survival analysis was used to compare the time to menopause between the LFHC and control groups and to assess other factors associated with age at menopause. RESULTS: The LFHC intervention did not affect the time to natural menopause overall (P = 0.72 for log-rank test comparing study groups; n = 699 events). An observed interaction between study group and baseline body mass index (BMI; P = 0.01) indicated that the intervention group experienced earlier menopause than did the control group when BMI was low and that a higher BMI was associated with later menopause in the intervention group only. Greater parity, weight, and education were associated with later menopause, and greater age at first birth and baseline smoking were associated with earlier menopause. CONCLUSIONS: Overall, the LFHC dietary intervention did not influence the timing of menopause. Factors associated with age at menopause in this population were consistent with those reported in other populations.     

Preeclampsia, pregnancy-related hypertension, and breast cancer risk

Pregnancy conditions accompanied by high blood pressure, such as preeclampsia and pregnancy-related hypertension, have been associated with a lower risk of breast cancer in several epidemiologic studies. It is unknown whether length of gestation or multiple occurrence of these conditions alters the association with breast cancer. It is also unknown whether the inverse association between preeclampsia and breast cancer risk is modified by menopausal status at breast cancer diagnosis. Using data from a large, population-based case-control study of breast cancer conducted on Long Island, New York, during 1996-1997, the authors examined these questions among ever-parous women (1,310 cases and 1,385 controls) using multivariate logistic models. Preeclampsia was inversely associated with breast cancer (odds ratio = 0.7, 95% confidence interval: 0.5, 1.0); this association was even stronger among women who had multiple occurrences of preeclampsia (odds ratio = 0.3, 95% confidence interval: 0.1, 0.9). The risk reduction was more pronounced among postmenopausal women. Gestation length did not substantially alter the relation between preeclampsia and breast cancer risk. Pregnancy-related hypertension was also inversely associated with breast cancer risk, but the relations were not statistically significant after adjustment for preeclampsia. These data suggest that pregnancy conditions related to hypertension, particularly preeclampsia, play a role in reducing breast cancer risk. Possible biologic mechanisms underpinning these associations should be further explored.     

Associations between soy, diet, reproductive factors, and mammographic density in Singapore Chinese women

Although the evidence is not completely consistent, soy intake has been inversely associated with breast cancer risk, and the strongest results have been observed in certain Asian populations. To address this issue and to examine the association between mammographic density and reproductive factors in this population, we conducted a cross-sectional analysis of mammograms and validated food-frequency questionnaires from 380 Chinese women living in Singapore. Percent mammographic density, a biomarker for breast cancer risk, was assessed using a validated computer-assisted method. We used generalized linear models to estimate mean mammographic density by quartiles of soy intake and intake of other dietary factors while adjusting for potential confounders. Percent mammographic density was inversely associated with age, body mass index, parity, breastfeeding, and soy intake. The difference in mammographic density between the highest and lowest quartiles of soy intake was 4-5%; this difference was statistically significant for soy protein and soy isoflavone intake and is similar in magnitude to what has been reported in Western populations when women undergo menopause or commence hormone therapy. We found no evidence that high fiber, fruit, or vegetable intake has protective effects on mammographic density. Our results suggest that the effect of soy intake on percent mammographic density is moderate but possibly of clinical relevance.     

Intake of specific carotenoids and essential fatty acids and breast cancer risk in Montreal, Canada

BACKGROUND: Evidence from previous investigations into the possible role of dietary and serum carotenoid concentrations in the etiology of breast cancer is inconsistent. No study has examined the combined effect of carotenoids and essential fatty acids on the risk of breast cancer. OBJECTIVE: The objective was to assess the possible association between specific and total carotenoids and breast cancer risk and to evaluate the effect modification by diet-related fatty acids and lifestyle factors in the development of breast cancer. DESIGN: A population-based case-control study involving 414 incident cases and 429 controls was conducted in French Canadians in Montreal. Dietary intake was estimated with the use of a validated food-frequency questionnaire in face-to-face interviews. RESULTS: No significant association was apparent between any of the individual or total carotenoids and the risk of breast cancer after adjustment for major underlying determinants of breast cancer. In premenopausal women who ever smoked, an increased risk was related to alpha-carotene [odds ratio (OR) for the upper relative to the lowest quartiles of intake: 2.40; 95% CI: 0.90, 6.41; P for trend = 0.046]. Conversely, a reduced risk was related to beta-carotene (OR: 0.57; 95% CI: 0.26, 1.24; P for trend = 0.05) in women who never used hormone replacement therapy. In postmenopausal women, total carotenoids were positively associated with breast cancer risk in those with a high arachidonic acid intake (OR: 1.92; 95% CI: 0.93, 3.94; P = 0.028 for trend) and inversely associated in those with a high docosahexaenoic acid intake (OR: 0.52; 95% CI: 0.25, 1.07; P for trend = 0.054). CONCLUSION: These findings suggest that the combined high intake of total carotenoids and docosahexaenoic acid may reduce the risk of breast cancer.     

Case-control study of physical activity and breast cancer risk among premenopausal women in Germany

Important aspects of the recognized inverse relation between physical activity and breast cancer risk are still under discussion. Data on physical activity from sports, occupational activity, household tasks, walking, and cycling by reported frequency, duration, and intensity during adolescence and young adulthood were collected in 1999-2000 from 360 premenopausal breast cancer cases and 886 controls who had previously participated in a German population-based case-control study. In multivariate conditional logistic regression, no association between total physical activity and premenopausal breast cancer was found in two age periods. For women who were active during both periods, the adjusted odds ratio was 0.83 (95% confidence interval: 0.60, 1.14). When both age periods were combined, higher quartiles of total physical activity compared with the lowest quartile showed adjusted odds ratios of 0.97, 0.68, and 0.94. Only the effect of moderately high physical activity was statistically significant. Analyses by type of activity revealed significant protective effects for women who reported the highest levels of cycling activities (adjusted odds ratio = 0.66, 95% confidence interval: 0.45, 0.97). These data do not suggest an inverse monotonic association between total physical activity and breast cancer risk in premenopausal women. The study prevalence of cycling and walking for transportation demonstrated that national habits need consideration in the exposure assessment.     

体重指数对绝经前后Luminal型乳腺癌预后的 影响分析

摘要:目的　探讨体重指数（BMI）对绝经前后Luminal型乳腺癌预后的影响。方法　回顾性收集四川省肿瘤医院2005-2010年收治的298例女性原发Luminal型乳腺癌病例资料并进行随访,中位随访时间为39个月。将病例根据绝经状态分层,采用COX比例风险模型分析不同BMI（BMI＜23.0 kg/m2和BMI≥23.0 kg/m2）对乳腺癌病例无病生存期（DFS）的影响。结果　绝经前和绝经后Luminal型乳腺癌患者的平均BMI分别为（22.77±2.67）kg/m2和（24.47±3.63）kg/m2,差异有统计学意义（P＜0.001）,BMI＜23.0 kg/m2和BMI≥23.0 kg/m2的绝经前Luminal型乳腺癌患者的5年无病生存率分别为78.9%和60.7%（P＝0.036）,BMI≥23 kg/m2可显著增加绝经前Luminal型乳腺癌复发转移的风险（调整HR＝2.451,95%CI:1.100～5.459）,BMI对绝经后Luminal型乳腺癌DFS的影响无统计学意义。结论　高BMI是影响绝经前Luminal型乳腺癌预后的不良因素。     

A pilot study of mammographic density patterns among Japanese women.

Mammographic density patterns, which refer to the distribution of fat, connective, and epithelial tissue in the healthy female breast, have been shown to be related to breast cancer risk. We used a quantitative method to assess mammographic densities in 41 mammograms from women in Japan without a diagnosis of breast cancer. Information about reproductive behavior and family history for breast cancer was available from a questionnaire. The statistical analysis applied Spearman correlation coefficients and multiple linear regression. The breast size as measured on the cranio-caudal view of the mammogram was approximately 12% larger, the size of the dense areas was 20% smaller, and the mean percent mammographic densities were 30% greater among premenopausal than among postmenopausal women. We found a strong relation between age at menarche and mammographic densities in premenopausal women and significant associations for age, family history of breast cancer, and age at menopause with mammographic densities in postmenopausal women. These preliminary data will be used to plan a future study that will compare mammographic density patterns and the relative importance of dietary, reproductive, and anthropometric factors between women in Japan and in the United States.     

Dietary intake of soy protein and tofu in association with breast cancer risk based on a case-control study

Soy food and its constituents may protect against breast cancer, but the association between soy intake and decreased breast cancer risk is inconsistent. We evaluated the relationship between breast cancer risk and the dietary intake of soy protein as measured by total soy food and tofu intake. Histologically confirmed cases (n = 362) were matched to controls by age (within 2 yr) and menopausal status. High soy protein intake was associated with reduced breast cancer risk in analyses adjusted for potential confounders including dietary factors among premenopausal women (odds ratio [OR] = 0.39 in the highest quintile, 95% confidence interval [CI] = 0.22-0.93, P for trend = 0.03) and postmenopausal women (OR = 0.22, 95% CI = 0.06-0.88, P for trend = 0.16). We also found an inverse association between total tofu intake and breast cancer risk among premenopausal women (for total tofu intake, OR = 0.23 in the highest quintile, 95% CI = 0.11-0.48, P for trend < 0.01; for at least 1 serving of tofu as the main ingredient per day, OR = 0.26, 95% CI = 0.13-0.55, P for trend < 0.01). We concluded that increased regular soy food intake at a level equivalent to traditional Korean consumption levels may be associated with a reduced risk of breast cancer, and this effect is more pronounced in premenopausal women.     

Dietary glycemic index, glycemic load, and the risk of breast cancer in an Italian prospective cohort study

BACKGROUND: Interest in the roles of glycemic index (GI) and glycemic load (GL) in breast cancer etiology has been stimulated by indications that disease risk is linked to insulinemia, sex hormone bioavailability, and insulin-like growth factor 1. OBJECTIVE: We aimed to determine whether GI and GL were associated with the risk of breast cancer in a cohort of Italian women volunteers from Northern Italy, who enrolled between 1987-1992 in the Hormones and Diet in the Etiology of Breast Tumors Study (ORDET Study). DESIGN: Volunteers completed a semiquantitative food-frequency questionnaire, and anthropometric and lifestyle data were collected. Dietary GI and GL in relation to breast cancer risk were examined in 8926 cohort women, including 289 with breast cancer identified after a mean follow-up of 11.5 y. RESULTS: The relative risk (RR) of breast cancer in the highest (versus lowest) quintiles of GI and GL was 1.57 (95% CI: 1.04, 2.36; P for trend = 0.040) and 2.53 (95% CI: 1.54, 4.16; P for trend = 0.001), respectively. Total carbohydrate intake was not associated with greater breast cancer risk, but high carbohydrate from high-GI foods was. When women were categorized by baseline menopausal status and body mass index (BMI; in kg/m(2)), the increased risk of dietary GL was confined to those who were premenopausal (RR = 3.89; 95% CI: 1.81, 8.34) and who had normal BMI (ie, <25) (RR = 5.79; 95% CI: 2.60, 12.90) (P for trend = 0.001 for both). CONCLUSIONS: A high-GL diet may increase the risk of breast cancer in Italian women. The effect is particularly evident in premenopausal women and those with BMI < 25.