肥胖与乳腺癌

 肥胖被证实是乳腺癌等恶性肿瘤的危险因素之一。大量流行病学资料显示肥胖与乳腺癌的发生发展密切相关,其发病机制可涉及雌激素、胰岛素、瘦素、脂联素、炎症因子等肥胖相关因子。因此,维持正常体重可能有助于乳腺癌的防治。     

肥胖与乳腺癌

肥胖被证实是乳腺癌等恶性肿瘤的危险因素之一。大量流行病学资料显示肥胖与乳腺癌的发生发展密切相关,其发病机制可涉及雌激素、胰岛素、瘦素、脂联素、炎症因子等肥胖相关因子。因此,维持正常体重可能有助于乳腺癌的防治。     

代谢综合征与乳腺癌关系的研究进展

摘 要：大量流行病学资料以及临床研究已证实代谢综合征与乳腺癌的发生发展和预后密切相关,其影响机制可能涉及胰岛素、胰岛素样生长因子-1、胰岛素抵抗、内源性激素、瘦素、脂联素、炎症因子等多种因子。因此,控制血糖、体重和血脂可能是预防乳腺癌发生和复发转移的有利措施。     

肥胖与乳腺癌发病相关性的研究进展

摘 要：肥胖通过多种分子机制影响乳腺癌的发生，包括胰岛素及胰岛素样生长因子、炎症细胞因子、瘦素及脂联素和雌激素的生理改变，但其影响因女性绝经状态不同而有所区别。大部分研究支持肥胖与绝经前乳腺癌风险呈负相关；而对于绝经后女性，肥胖会增加其罹患乳腺癌的风险。     

肥胖与肿瘤

肥胖是乳腺癌、大肠癌等多种肿瘤发生的危险因素.研究表明,肥胖通过胰岛素和胰岛素样生长因子-1(IGF-1)、瘦素、脂肪细胞因子、性激素等多种因子影响癌症的发生和发展.研究肥胖与癌症发生发展中的作用及机制将为肿瘤的预防和治疗提供新的思路.     

肥胖相关肿瘤发生机制和防治研究进展

超重、肥胖是包括心血管疾病、2 型糖尿病和代谢综合征等多种疾病的主要危险因素,并对恶性肿瘤风险和预后产 生负面影响。 肥胖已被证明是一些恶性肿瘤的独立危险因素,包括乳腺癌、子宫内膜癌、卵巢癌、胃癌、结直肠癌、肾癌、食管 腺癌、胰腺导管腺癌和肝癌等。 但关于肥胖促进肿瘤发生的机制知之甚少,目前主要集中在肥胖后的胰岛素抵抗、脂肪因子 失调、性激素失衡、全身炎症、免疫系统变化和肠道菌群失调。 这些机制并不是单独地在起作用,而是以炎症为基础,相互联 系、相互促进肿瘤的发生。 肥胖对恶性肿瘤的发展和死亡率的影响,大部分可以通过饮食结构的调整和增加体育锻炼来预 防。 以抗炎为基础的药物治疗可作为预防的优先策略,减重手术也为肥胖相关恶性肿瘤的预防和治疗提供更多选择。 本文 将综述超重和肥胖促进恶性肿瘤发生、发展的机制,并探讨未来肥胖患者的肿瘤预防和治疗措施。     

肥胖与乳腺癌关系的研究进展

乳腺癌是世界女性最常见的恶性肿瘤之一,每年新确诊的癌症病例中有1/10是女性乳腺癌,每年约有120万女性罹患乳腺癌,约50万人死于该病[1]。资料显示,全世界有9.8%的男性和13.8%的女性被认为是肥胖者[2]。肥胖已经成为全球的重大公共卫生问题,同时,流行病学资料显示肥胖能增加乳腺癌风险[3],因而肥胖与乳腺癌的关系日益受到学者们的重视。本文从肥胖人群中乳腺癌患者的临床及生物学机制等方面对肥胖与乳腺癌的研究进展作一综述。     

肥胖与乳腺癌关系的研究进展

0 引言 乳腺癌目前已成为全球女性最常见的恶性肿瘤之一,其发病率和死亡率在女性肿瘤中已位居第二[1].据世界卫生组织(world health organization,WHO)2008年的数据统计,全球已有440万女性患乳腺癌[2].预计到2021年,中国将有250万女性患乳腺癌[3].目前研究表明,乳腺癌的危险因素有很多,如年龄、家族史、初潮时间、生育情况、乳腺良性肿瘤史、肥胖等[1,4].其中,肥胖与乳腺癌的关系近年来受到广泛关注.     

脂联素与乳腺癌的相关性

 脂联素是至今发现的惟一与肥胖呈负相关的脂肪细胞特异性蛋白,具有增强胰岛素敏感性、抗动脉硬化、抗炎作用。最近有研究报道,脂联素与多种肥胖相关恶性肿瘤的发生发展密切相关,尤其是绝经后乳腺癌。肥胖是乳腺癌发生的独立危险因素,近来关于脂联素与乳腺癌的关系及其作用机制、信号通路的研究有很大进展。     

胰岛素、IGF及IGFBP与乳腺癌相关性研究

胰岛素抵抗、胰岛素样生长因子(IGF)和胰岛素样生长因子结合蛋白(IGFBP)-3的水平升高及IGFBP-1的水平降低可能与乳腺癌发生有关。合理的饮食、规律的体育锻炼，可降低肥胖女性胰岛素、IGF及IGFBP-3水平，预防乳腺癌发生。药物治疗可以改变胰岛素水平，降低IGF-Ⅰ生物效应，提高乳腺癌患者术后疗效。     

Overweight, obesity, diabetes, and risk of breast cancer: interlocking pieces of the puzzle

We considered epidemiological data on overweight, diabetes, insulin, and breast cancer. Overweight is inversely related to premenopausal breast cancer, but there is definite evidence that, as compared with normal weight women, the relative risk (RR) for postmenopausal breast cancer is around 1.5 for overweight women and >2 for obese women, and that the association is stronger in elderly women. Overweight and obesity are strongly related to diabetes. Diabetes is associated with postmenopausal breast cancer, too, with summary RRs from meta-analyses of 1.15-1.20, but not with premenopausal breast cancer (RR, 0.9). There is no consistent evidence that fasting insulin is related to breast cancer risk. Thus, although overweight and obesity are strongly related to postmenopausal breast cancer, diabetes is only moderately related to it. Given the extent of the association, and the likely residual confounding by overweight, inference on causality for the diabetes-breast cancer relation remains open to discussion.     

The Obesity and the Risk of Breast Cancer among Pre and Postmenopausal Women

Background: Breast cancer is the most common cancer among women worldwide and the obesity is one ofthe factors related to the risk of breast cancer mainly in postmenopausal women. This study investigated the associationbetween obesity in pre- and postmenopausal women with the development of breast cancer and the expression ofestrogen, progesterone, HeR-2 and triple-negative (TN) receptors. Methods: A case-control study was conductedon 100 patients with recently diagnosed breast cancer and 400 age-matched controls. The women were divided intopre- and post-menopausal groups. Results: The multivariate analysis showed that postmenopausal women witha BMI ≥ 30 kg/m2 at pre-diagnosis and at the most recent measurement were 1.50 (95% CI 1.06-2.13) and 1.56(95% CI 1.11-2.21) times more likely to develop breast cancer, respectively. These women had a prevalence ofobesity of 27.7% when considering pre-diagnosis BMI and 29.4% when analyzing the indicator of recent BMI. Whenonly the cases regarding the presence of obesity with clinicopathological variables were analyzed, a total of 95.2% ofthe postmenopausal women with pre-diagnostic obesity according to BMI presented the positive estrogen receptor(ER) subtype. Conclusions: In Brazilian women, there is an association between obesity and the risk of breast cancerpostmenopause; moreover, there is an association between the occurrence of the positive ER subtype in postmenopausalwomen and pre-diagnostic obesity according to BMI.     

Phytoestrogens,body composition,and breast cancer

To the extent that diet is involved in the etiology of breast cancer, its effect may be mediated, in part, through hormonal mechanisms. It has been suggested that the consumption of phytoestrogens is related inversely to breast cancer risk. Phytoestrogens are weak estrogens of plant derivation that may have antiestrogenic effects through competitively binding to estrogen receptors, thus diminishing the binding of stronger endogenous estrogens. This paper advances the hypothesis that, through this mechanism, dietary phytoestrogens may attenuate the adverse consequences of obesity on the development of postmenopausal breast cancer. Such an association might partly explain the low breast cancer rates observed among postmenopausal Hispanic women despite their greater adiposity, an important breast cancer risk factor. This hypothesis would lead us to expect that obesity increases the risk of postmenopausal breast cancer in women consuming small quantities of phytoestrogens but does not increase risk in women consuming larger quantities. If the hypothesis is confirmed, such an association could have important implications for reducing breast cancer risk through diet, using naturally occurring substances, particularly in women for whom postmenopausal obesity is an important health concern.This research was supported in part by a grant from the Fashion Times II committee in support of breast cancer research.     

Obesity and screening for breast, cervical, and colorectal cancer in women: a review

The literature examining obesity as a barrier to screening for breast, cervical, and colorectal cancer has not been evaluated systematically. With the increasing prevalence of obesity and its impact on cancer incidence and mortality, it is important to determine whether obesity is a barrier to screening so that cancers among women at increased risk because of their body size can be detected early or prevented entirely. On the basis of 32 relevant published studies (10 breast cancer studies, 14 cervical cancer studies, and 8 colorectal cancer studies), the authors reviewed the literature regarding associations between obesity and recommended screening tests for these cancer sites among women in the U.S. The most consistent associations between obesity and screening behavior were observed for cervical cancer. Most studies reported an inverse relation between decreased cervical cancer screening and increasing body size, and several studies reported that the association was more consistent among white women than among black women. For breast cancer, obesity was associated with decreased screening behavior among white women but not among black women. The literature regarding obesity and colorectal cancer screening adherence was mixed, with some studies reporting an inverse effect of body size on screening behavior and others reporting no effect. Overall, the results indicated that obesity most likely is a barrier to screening for breast and cervical cancers, particularly among white women; the evidence for colorectal cancer screening was inconclusive. Thus, efforts to identify barriers and increase screening for breast and cervical cancers may be targeted toward obese women, whereas outreach to all women should remain the objective for colorectal cancer screening programs.     

Obesity and Cancer

Weight, weight gain, and obesity account for approximately 20% of all cancer cases. Evidence on the relation of each to cancer is summarized, including esophageal, thyroid, colon, renal, liver, melanoma, multiple myeloma, rectum, gallbladder, leukemia, lymphoma, and prostate in men; and postmenopausal breast and endometrium in women. Different mechanisms drive etiologic pathways for these cancers. Weight loss, particularly among postmenopausal women, reduces risk for breast cancer. Among cancer patients, data are less robust, but we note a long history of poor outcomes after breast cancer among obese women. While evidence on obesity and outcomes for other cancers is mixed, growing evidence points to benefits of physical activity for breast and colon cancers. Dosing of chemotherapy and radiation therapy among obese patients is discussed and the impact on therapy‐related toxicity is noted. Guidelines for counseling patients for weight loss and increased physical activity are presented and supported by strong evidence that increased physical activity leads to improved quality of life among cancer survivors. The “Five A's” model guides clinicians through a counseling session: assess, advise, agree, assist, arrange. The burden of obesity on society continues to increase and warrants closer attention by clinicians for both cancer prevention and improved outcomes after diagnosis.     

Comparison of anthropometric measures as predictors of cancer incidence: A pooled collaborative analysis of 11 Australian cohorts

Obesity is a risk factor for cancer. However, it is not known if general adiposity, as measured by body mass index (BMI) or central adiposity [e.g., waist circumference (WC)] have stronger associations with cancer, or which anthropometric measure best predicts cancer risk. We included 79,458 men and women from the Australian and New Zealand Diabetes and Cancer Collaboration with complete data on anthropometry [BMI, WC, Hip Circumference (HC), WHR, waist to height ratio (WtHR), A Body Shape Index (ABSI)], linked to the Australian Cancer Database. Cox proportional hazards models assessed the association between each anthropometric marker, per standard deviation and the risk of overall, colorectal, post‐menopausal (PM) breast, prostate and obesity‐related cancers. We assessed the discriminative ability of models using Harrell's c‐statistic. All anthropometric markers were associated with overall, colorectal and obesity‐related cancers. BMI, WC and HC were associated with PM breast cancer and no significant associations were seen for prostate cancer. Strongest associations were observed for WC across all outcomes, excluding PM breast cancer for which HC was strongest. WC had greater discrimination compared to BMI for overall and colorectal cancer in men and women with c‐statistics ranging from 0.70 to 0.71. We show all anthropometric measures are associated with the overall, colorectal, PM breast and obesity‐related cancer in men and women, but not prostate cancer. WC discriminated marginally better than BMI. However, all anthropometric measures were similarly moderately predictive of cancer risk. We do not recommend one anthropometric marker over another for assessing an individuals' risk of cancer.     

A prospective study of body size and breast cancer in black women.

The relation of body mass index (BMI) and weight gain to breast cancer risk is complex, and little information is available on Black women, among whom the prevalence of obesity is high. We assessed BMI and weight gain in relation to breast cancer risk in prospective data from the Black Women's Health Study. In 1995, 59,000 African American women enrolled in the Black Women's Health Study by completing mailed questionnaires. Data on anthropometric factors were obtained at baseline and every 2 years afterwards. In 10 years of follow-up, 1,062 incident cases of breast cancer occurred. Incidence rate ratios (IRR) were computed in multivariable Cox proportional hazards regression. BMI at age 18 years of >/=25 relative to <20 was associated with a reduced risk of breast cancer among both premenopausal women (IRR, 0.68; 95% confidence interval, 0.46-0.98) and postmenopausal women (IRR, 0.53; 95% confidence interval, 0.35-0.81). There was an inverse association of current BMI with premenopausal breast cancer but no association with postmenopausal breast cancer, either overall or among never-users of hormone therapy. Weight gain was not associated with postmenopausal breast cancer risk. In analyses restricted to breast cancers that were estrogen and progesterone receptor positive, IRRs for current BMI and weight gain were elevated but not statistically significant. The findings indicate that being overweight at age 18 years is associated with a reduced risk of both premenopausal and postmenopausal breast cancer in African American women. Understanding the reasons for the association may help elucidate the pathways through which adolescent exposures influence breast cancer risk. The lack of association of obesity with receptor-negative tumors in postmenopausal African American women may partially explain why breast cancer incidence in older Black women is not high relative to other ethnic groups in spite of the high prevalence of obesity in Black women.     

Adult weight change and incidence of premenopausal breast cancer

Overweight and obesity are inversely related to the risk of breast cancer among premenopausal women. We assessed the association between adult weight change since age 18 years with the risk of breast cancer among premenopausal women to explore whether weight gain was associated with a decrease in risk and weight loss was associated with an increase in risk. A total of 56,223 premenopausal participants in the Nurses' Health Study and 109,385 premenopausal participants in the Nurses' Health Study II were prospectively followed for up to 32 years and 18 years, respectively, and weight change since age 18 years was assessed biennially. The incidence of invasive breast cancer was assessed throughout follow-up. Weight loss of 5 kg or more since age 18, maintained for at least 4 years, was related to lower incidence of premenopausal breast cancer, compared to maintaining a stable weight, but this relation was of borderline statistical significance (covariate-adjusted HR = 0.75; 95% CI 0.52-1.09). Weight gain since age 18 years was also inversely related to breast cancer incidence among premenopausal women (covariate-adjusted p for trend = 0.01), but the association weakened after controlling for weight at age 18 and did not reach statistical significance (p for trend = 0.08). Although obesity and breast cancer among premenopausal women are inversely related, weight loss since age 18 years did not increase and weight gain did not significantly decrease the risk of premenopausal breast cancer among participants in the large prospective cohorts of NHS and NHS II.     

Breast cancer incidence trends in deprived and affluent Scottish women

OBJECTIVE : Breast cancer is commoner in the affluent and breast cancer rates in many countries are rising; it remains unclear whether this incidence rise is consistent across the different socio-economic groups. The rising incidence of breast cancer may be related to changes in population risk factor profiles. This study aimed to determine breast cancer incidence trends in women of different socio-economic categories and whether these trends were related to breast cancer risk factor trends. DESIGN : Data on breast cancer incidence rates by deprivation quintile in Scotland 1991-2000 were analysed using linear regression. Data on first births at late maternal age, BMI trends (based on the Scottish Health Surveys) and breast screening uptake trends in the different categories were also analysed and their relation to breast cancer incidence trends explored. POPULATION AND SETTING : Breast cancer incidence data was based on all women in Scotland. BMI data was based on representative cross-sectional survey data from the Scottish Health Surveys-women in the 1995, 1998 and 2003 surveys were 16-64, 16-74 and aged 16 and over, respectively. First birth data was based on all women aged 35-39 in Scotland. Breast screening uptake data was studied in women of screening age, that is, aged 50-64. RESULTS : Breast cancer incidence rates in Scottish women are rising in parallel across all socio-economic categories and the incidence gap between deprived and affluent still remains. Since the late 1980s, numbers of first birth in Scottish women aged 35-39 have risen dramatically, especially in the affluent, but numbers were stable before this. The prevalence of obesity and mean BMI has increased over time in all socio-economic classes but BMI continues to be higher in the deprived. Uptake of screening invitations has increased in all socio-economic groups. CONCLUSIONS : Breast cancer is rising in women of all socio-economic status in Scotland and the deprived-affluent gap remains. Trends in late age at first pregnancy, prevalence of obesity and screening uptake do not fully explain the observed trends.     

Collaborative modeling of the impact of obesity on race-specific breast cancer incidence and mortality

Obesity affects multiple points along the breast cancer control continuum from prevention to screening and treatment, often in opposing directions. Obesity is also more prevalent in Blacks than Whites at most ages so it might contribute to observed racial disparities in mortality. We use two established simulation models from the Cancer Intervention and Surveillance Modeling Network (CISNET) to evaluate the impact of obesity on race-specific breast cancer outcomes. The models use common national data to inform parameters for the multiple US birth cohorts of Black and White women, including age- and race-specific incidence, competing mortality, mammography characteristics, and treatment effectiveness. Parameters are modified by obesity (BMI of ??30?kg/m²) in conjunction with its age-, race-, cohort- and time-period-specific prevalence. We measure age-standardized breast cancer incidence and mortality and cases and deaths attributable to obesity. Obesity is more prevalent among Blacks than Whites until age 74; after age 74 it is more prevalent in Whites. The models estimate that the fraction of the US breast cancer cases attributable to obesity is 3.9?C4.5?% (range across models) for Whites and 2.5?C3.6?% for Blacks. Given the protective effects of obesity on risk among women <50?years, elimination of obesity in this age group could increase cases for both the races, but decrease cases for women ??50?years. Overall, obesity accounts for 4.4?C9.2?% and 3.1?C8.4?% of the total number of breast cancer deaths in Whites and Blacks, respectively, across models. However, variations in obesity prevalence have no net effect on race disparities in breast cancer mortality because of the opposing effects of age on risk and patterns of age- and race-specific prevalence. Despite its modest impact on breast cancer control and race disparities, obesity remains one of the few known modifiable risks for cancer and other diseases, underlining its relevance as a public health target.