Body Size and Risk of Breast Cancer

University of Wisconsin Comprehensive Cancer Center, Madison 53706, USA.
American Journal of Epidemiology (Impact Factor: 5.23). 07/1997; 145(11):1011-9. DOI: 10.1093/oxfordjournals.aje.a009057
Source: PubMed


The relation between body size and breast cancer remains uncertain, particularly with regard to differences between pre- and postmenopausal women. The authors examined whether height, weight, body mass index, and weight change were associated with breast cancer risk among pre- and postmenopausal women. This population-based case-control study included women aged 20-74 years (n = 6,548) who were diagnosed with invasive breast cancer during 1988-1991 in Maine, Massachusetts, New Hampshire, and Wisconsin. Similarly aged control women (n = 9,057) were selected at random from driver's license files and Health Care Financing Administration files. Height, weight, and information on other breast cancer risk factors were ascertained by telephone interview, and logistic regression was used to estimate multivariate-adjusted odds ratios and 95% confidence intervals. Among premenopausal women, the adjusted odds ratio for the upper quintile group of height relative to the lowest was 1.36 (95% confidence interval (CI) 1.05-1.76). The heaviest premenopausal women had a lower risk (odds ratio (OR) = 0.87, 95% CI 0.70-1.10). Among postmenopausal women, the adjusted odds ratios were higher for the upper quintile categories of both height (OR = 1.27, 95% CI 1.11-1.45) and weight (OR = 1.57, 95% CI 1.37-1.79). Weight gain since ages 18 and 35 years was associated with increased postmenopausal breast cancer risk, and risk was lower in women who had lost weight. These findings suggest that programs to avoid weight gain merit study as a means to reduce risk of postmenopausal breast cancer.

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Available from: Polly A Newcomb
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    • "Coates et al. demonstrated a statistically significant 36% reduction in risk when weight loss was achieved with respect to low-grade tumors only in pre-menopausal women (41). However, contrasting reports from three studies have shown that weight loss over a prolonged interval did not significantly reduce risk of developing breast cancer (42–44). The Women’s Health Initiative (WHI) Randomized Controlled Dietary Modification Trial in post-menopausal women indicated that a dietary intervention group exhibited 9% non-significant lower risk compared to the control group after 8 years of follow-up (45). "
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    ABSTRACT: Epidemiologic studies demonstrate that obesity is associated with an aggressive subtype of breast cancer called basal-like breast cancer (BBC). Using the C3(1)-TAg murine model of BBC, we previously demonstrated that mice displayed an early onset of tumors when fed obesogenic diets in the adult window of susceptibility. Obesity was also shown to elevate mammary gland expression and activation of hepatocyte growth factor (HGF)/c-Met compared to lean controls, a pro-tumorigenic pathway associated with BBC in patients. Epidemiologic studies estimate that weight loss could prevent a large proportion of BBC. We sought to investigate whether weight loss in adulthood prior to tumor onset would protect mice from accelerated tumorigenesis observed in obese mice. Using a life-long model of obesity, C3(1)-TAg mice were weaned onto and maintained on an obesogenic high fat diet. Obese mice displayed significant elevations in tumor progression, but not latency or burden. Tumor progression was significantly reversed when obese mice were induced to lose weight by switching to a control low fat diet prior to tumor onset compared to mice maintained on obesogenic diet. It is likely that other factors regulated tumor progression, hence we investigated the HGF/c-Met pathway known to regulate tumorigenesis. Importantly, HGF/c-Met expression in normal mammary glands and c-Met in tumors was elevated with obesity and was significantly reversed with weight loss. Changes in tumor growth could not be explained by measures of HGF action including phospho-AKT or phospho-S6. Other mediators associated with oncogenesis such as hyperinsulinemia and a high leptin/adiponectin ratio were elevated by obesity and reduced with weight loss. In sum, weight loss significantly blunted the obesity-responsive pro-tumorigenic HGF/c-Met pathway and improved several metabolic risk factors associated with BBC, which together may have contributed to the dramatic reversal of obesity-driven tumor progression.
    Full-text · Article · Jul 2014 · Frontiers in Oncology
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    • "In many industrialized countries, over one-fifth of the adult population is obese, and this proportion is also increasing in developing countries [2]. It is known that obesity has been strongly associated with increased risks, and it has been found to be one of the common factors in breast cancer risk of postmenopausal women [3,4]. Interventions of obesity -related provide an important idea for breast cancer prevention. "
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    ABSTRACT: Published results suggests that high adiponectin level may decrease the risk of breast cancer. However, available evidence on breast cancer is conflicting. Therefore a meta-analysis was performed to assess the association between blood adiponectin and breast cancer risk. PubMed database, Web of Science, Elsevier Science, Springer Link and bibliographies of retrieved articles were searched for epidemiological studies published up to March 2013. Meta-analysis was performed on the combined effect values (OR) as well as standardized mean difference (SMD) including 17 studies. Fixed or random effect pooled measure was selected on the basis of homogeneity test among studies. The publication bias was assessed by the Egger's regression asymmetry test and Begg's rank correlation test with Begg's funnel plot. Subgroup analyses and sensitivity analysis were also performed. A total of 13 studies involving 3578 breast cancer cases and 4363 controls contributed to the OR analysis. The high adiponectin level did not significantly affect breast cancer risk (OR=0.902, 95% CI=0.773-1.053). After excluding articles that were the key contributors to between-study heterogeneity, the OR of high adiponectin level was associated with decreased breast cancer risk (OR=0.838, 95% CI=0.744-0.943). There was a significantly association between high adiponectin level and postmenopausal breast cancer women (OR=0.752, 95%CI=0.604-0.936); and it was not associated with premenopausal breast cancer women (OR=0.895, 95%CI=0.638-1.256). The result of pooled measure on SMD was that the high adiponectin level was associated with decreased breast cancer risk (SMD= -0.348, 95% CI= -0.533--0.614) after excluding articles which were the key contributors to between-study heterogeneity. Our findings indicate that high adiponectin level might decrease the risk of postmenopausal breast cancer. More randomized clinical trials and observational studies are needed to confirm this association with underlying biological mechanisms in the future.
    Preview · Article · Aug 2013 · PLoS ONE
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    • "This epidemic poses a dire threat to public health, as obesity can play a role in the pathogenesis of numerous diseases, including breast cancer. In postmenopausal women, obesity increases breast cancer risk by approximately 40% [3-5]. A large body of evidence has also established that obesity is associated with a worse breast cancer prognosis for both pre- and postmenopausal women. "
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    ABSTRACT: Epidemiological and clinical studies indicate that obesity is associated with a worse postmenopausal breast cancer prognosis and an increased risk of endocrine therapy resistance. However, the mechanisms mediating these effects remain poorly understood. Here we investigate the molecular pathways by which obesity-associated circulating factors in the blood enhance estrogen receptor alpha (ERalpha) positive breast cancer cell viability and growth. Blood serum was collected from postmenopausal breast cancer patients and pooled by body mass index (BMI) category (Control: 18.5-24.9 kg/m2; Obese: [greater than or equal to] 30.0 kg/m2). The effects of patient sera on MCF-7 and T47D breast cancer cell viability and growth were examined by MTT and colony formation assays, respectively. Insulin-like growth factor receptor 1(IGF-1R), Akt, and ERK1/2 activation and genomic ER activity were assessed to determine their possible contribution to obese patient sera-induced cell viability and growth. To further define the relative contribution of these signaling pathways, cells grown in patient sera were treated with various combinations of ER, PI3K/Akt, and MAPK targeted therapies. Comparisons between cells exposed to different experimental conditions were made using one-way ANOVA and Student's t test. Cells grown in media supplemented with obese patient sera displayed greater cell viability and growth as well as IGF-1R, Akt, and ERK1/2 activation relative to control sera. Despite the lack of a significant difference in genomic ER activity following growth in obese versus control patient sera, we observed a dramatic reduction in cell viability and growth after concurrent inhibition of the ERand PI3K/Akt signaling pathways. Further, we demonstrated that ER inhibition was sufficient to attenuate obese serum-induced Akt and ERK1/2 activation. Together, this data suggests that obesity promotes greater ER positive breast cancer cell viability and growth through enhanced crosstalk between nongenomic ER signaling and the PI3K/Akt and MAPK pathways. Circulating factors in the serum of obese postmenopausal women stimulate ER positive breast cancer cell viability and growth by facilitating non-genomic ERcrosstalk with the PI3K/Akt and MAPK signaling pathways. These findings provide valuable insight into one mechanism by which obesity may promote ER positive postmenopausal breast cancer progression and endocrine therapy resistance.
    Full-text · Article · Jul 2013 · Breast cancer research: BCR
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