代谢综合征与乳腺癌的关系

代谢综合征(metabolic syndrome,MS)是以肥胖和胰岛素抵抗为中心的多种代谢性危险因素在个体内集结的状态,主要组分包括肥胖、高血糖、高胰岛素血症、血脂异常和高血压等。研究表明代谢综合征不仅是心血管病的危险因素,还与乳腺癌的发生和预后相关。本文综述代谢综合征与乳腺癌患病风险的关系及其致乳腺癌的可能机制,为乳腺癌的预防、治疗及预后提供新的策略。     

Birth weight,weight over the adult life course and risk of breast cancer

Breast cancer has been suggested to potentially have prenatal origins. We examined associations between birth weight, body mass index (BMI) at four-time points over 25 years of adulthood, and risk of postmenopausal breast cancer, with emphasis on whether the association between birth weight and risk of breast cancer was mediated by weight and height changes over the adult life course. Postmenopausal women (n = 70,397) aged 50–79 years without breast cancer at enrollment (1993–1998) were followed up to 25 years. Weight and height were measured at baseline. Birth weight, and weights at ages 18, 35 and 50 were self-reported. Breast cancer cases were centrally adjudicated. Compared to women with birth weight of 6–8 pounds, women with birth weight of <6 pounds had lower risk of breast cancer (HR = 0.88 95% CI: 0.79–0.99). 44% and 21% of the relationship between birth weight and breast cancer risk was mediated by adult height and weight at baseline, respectively. Birth weight of 8 pounds or more was not associated with risk of postmenopausal breast cancer. Weight gain in adulthood was associated with increased risk of breast cancer regardless of time periods. In conclusion, lower birthweight was associated with lower risk of postmenopausal breast cancer, and this reduction in risk was significantly mediated by childhood or adolescent growth, especially by adult height. Our data suggest that reaching and maintaining a healthy weight during adulthood is key in the prevention of breast cancer.     

A review of body size and breast cancer risk in Hispanic and African American women

Obesity is an epidemic in the United States, especially among Hispanics and African Americans. Studies of obesity and breast cancer risk have been conducted primarily in non-Hispanic whites. There have been few studies of the association between body mass index (BMI) or weight gain and the risk of breast cancer in minorities, and the results have been inconsistent. Because most studies are conducted primarily in non-Hispanic whites, the etiology of breast cancer in minorities is not well understood. The authors of the current report reviewed the literature on the association between obesity, weight, and weight gain and breast cancer in minorities using a combination of the Medical Subject Heading (MeSH) terms "obesity," "body mass index," "weight," "weight gain," "Hispanic," and "African American." Only publications in English and with both risk estimates and 95% confidence intervals were considered. Forty-five studies of body size and breast cancer risk in non-Hispanic whites were identified. After an exhaustive search of the literature, only 3 studies of body size and breast cancer were conducted in Hispanic women were identified, and only 8 such studies in African American women were identified. The results were inconsistent in both race/ethnicity groups, with studies reporting positive, inverse, and null results. Thus, as obesity rates among Hispanics and African Americans continue to rise, there is an urgent need to identify the roles that both obesity and adult weight gain play in the development of breast cancer in these minorities. Additional studies are needed to provide more understanding of the etiology of this disease and to explain some of the disparities in incidence and mortality.     

Cumulative exposure to premenopausal obesity and risk of postmenopausal cancer: A population-based study in Icelandic women

Obesity, often assessed at one point in time, is an established risk factor of several types of cancer, however, associations with cumulative exposure to obesity across the life course are not well understood. We investigated the relationship between combined measures of duration and intensity of premenopausal overweight and obesity and the incidence of postmenopausal breast, endometrial, and colorectal cancers in Icelandic women. Body mass index (BMI) trajectories between ages 20 and 50 of 88,809 women from the Cancer Detection Clinic Cohort were predicted using growth curve models. Indicators of overweight and obesity duration and intensity were computed and their association with risk of postmenopausal breast, endometrial, and colorectal cancers was examined using multivariate Cox models for subjects followed-up beyond the age of 50 (n = 67,488). During a mean follow-up of 17 years, incident events of 3,016 postmenopausal breast, 410 endometrial and 987 colorectal cancers were ascertained. Each 0.1 kg/m² per year increase in BMI between ages 20 and 50 was positively associated with risks of postmenopausal breast, endometrium and colorectal cancers with hazard ratios equal to 1.09 (95% Confidence Interval (CI):1.04–1.13), 1.31 (95% CI: 1.18–1.44) and 1.10 (95% CI: 1.00–1.21), respectively. Compared to women who were never obese, cumulative BMI × years of obesity were linearly positively associated with risk of endometrial cancer, whereas the association with breast cancer was initially positive, but leveled off with increasing cumulative BMI × years. Cumulative exposure to obesity may provide additional insights into the etiology of cancer and should be considered in future studies that assess obesity–cancer relationships.     

Weight change and risk of postmenopausal breast cancer (United States)

Objective: Although many studies have shown that higher weight increases the risk of postmenopausal breast cancer, some aspects of this association are unclear. In order to examine the risk associated with different patterns of weight change, we analyzed data from a large case–control study of postmenopausal breast cancer. Methods: Participants included women aged 50–79 years (n = 5031) who are newly diagnosed with invasive breast cancer in Massachusetts, New Hampshire, and Wisconsin. Similarly-aged population controls (n = 5255) were selected at random from driver's license files and Medicare beneficiary lists. Height, weight, and information on other breast cancer risk factors were ascertained by structured telephone interviews from 1992 to 1995, and logistic regression was used to estimate multivariable-adjusted odds ratios (OR) and 95% confidence intervals (CI). Results: Women in the top quintile groups for height at age 20, recent weight, and recent body mass index had significantly increased risks of breast cancer. Among women who reached their highest adult weight at younger ages (45 years), increasing weight loss since that age was associated with a reduced risk of postmenopausal breast cancer (OR 0.90, CI 0.84–0.98, per 5 kg). However, weight loss among women whose highest weight occurred after age 45 was not associated with risk (OR 1.00, CI 0.95–1.05, per 5 kg). Weight gain since the lowest adult weight increased risk by 8% for each 5 kg of gain (OR 1.08, CI 1.06–1.11). Temporary weight cycling (weight loss followed by weight gain) was not associated with increased risk. Conclusions: Weight gain clearly increased risk of postmenopausal breast cancer. These data lend further support to efforts aimed at helping women avoid weight gain as they age.     

Anthropometric measures and metabolic rate in association with risk of breast cancer (United States)

To investigate whether cancer risk-reduction seen in calorie-restricted animals also applies to breast cancer in women, we have analyzed data from the first National Health and Nutrition Examination Survey in the United States and subsequent follow-up surveys. During the follow-up of one to 155 months, 182 out of 7,622 women developed breast cancer. Due to biased under-reporting of dietary intake, the analysis did not examine calorie intake as an exposure variable, but rather focused on anthropometric measures and metabolic rate as biomarkers of nutritional balance. Multiple Cox regression analysis showed elevated odds ratios (OR) for height, elbow width, and skinfolds among postmenopausal women. ORs for the fifth quintile were 2.0 (95 percent confidence interval [CI]=1.0–3.8), 2.3 (CI=1.2–4.7), and 2.0 (CI=1.0–4.0), respectively. Weight (OR=2.5, CI=1.2–5.1) and resting metabolic rate (OR=2.0, CI=1.0–4.0) were significant relative to the second quintile. Bitrochanteric breadth, sitting height, body fat, body mass index, or combination variables were not associated with cancer risk. It was concluded that in the analysis of breast cancer data, skeletal measures ought to be considered as routine potential confounders, and that using measured rather than estimated metabolic rates may improve risk prediction.Drs Freni and Turturro are with the US Food and Drug Administration, National Center for Toxicological Research, Jefferson, AR, USA. Dr Eberhardt is with the US Centers for Disease Control, National Center for Health Statistics, Hyattsville, MD, USA. Dr Hine is with the University of Arkansas for Medical Sciences, Little Rock, AR. Address correspondence to Dr Freni, National Center for Toxicological Research, Division of Biometry and Risk Assessment, HFT-20, Jefferson, AR 72079, USA.     

Selenium and the risk of postmenopausal breast cancer in the DOM cohort

Summary Selenium has been claimed to have chemo-preventive properties. However, data showing that in humans selenium levels are already decreased prior to diagnosis of breast cancer were not available. Such information is mandatory before oral selenium supplementation in the primary prevention of (breast) cancer in humans is acceptable. This question of a preventive-potential of selenium was evaluated in a case-control study nested in a cohort, because this design allows determination of the time-order of preceding selenium levels and subsequent cancer risk.The cohort consisted of 5577 women aged 55–70 years from the DOM project, a population based breast cancer screening program in the Netherlands. Instrumental Neutron Activation Analysis was used to measure the selenium content of toenail clippings. The 69 cases of breast cancer found during follow-up after screening represent recent tumours since all women had a negative screening mammogram 3–5 years previously.No decreased selenium levels, as measured in nail clippings from the big toes, could be detected in cases-to-be, either when compared to 4 age matched controls per case or when compared with a random control group drawn from the entire cohort. On the contrary, a tendency for slightly higher selenium levels among future cancer cases was observed.As to the sensitivity of detecting differences in selenium by nail clippings, lower selenium could be detected in nails of current smokers. The smoking-related decrease in nail selenium level was of the same order as the differences between breast cancer cases and controls, but was independent of the breast cancer risk.Results are similar to a comparable study on premenopausal breast cancer and argue against a preventive role for selenium on breast cancer risk.     

Weight change in adulthood and risk of postmenopausal breast cancer: the HUNT study of Norway

Background:

Adult weight gain is associated with increased risk of postmenopausal breast cancer. Most previous studies are limited by using recalled or self-reported data, and it is not known if age-specific weight changes are important for breast cancer risk.

Methods:

In a Norwegian cohort of 28 153 women (and 900 incident breast cancers) with longitudinal anthropometric measurements over up to 30 years, we studied both overall and age-related weight changes in adulthood and risk of postmenopausal breast cancer.

Results:

Overall, weight gain in adulthood was associated with increased breast cancer risk (hazard ratio (HR) per kg per year 1.31, 95% confidence interval (CI) 1.11–1.54). Weight gain before (HR per kg per year 1.38, 95% CI 1.09–1.75) or around menopause (1.69, 95% CI 1.32–2.16) was associated with increased risk, but there was no clear risk increase associated with later weight gain (HR per kg per year 0.92, 95% CI 0.73–1.18).

Conclusion:

Weight gain in adulthood was associated with increased risk of breast cancer. Our results suggest that weight gain before and around menopausal age may be particularly important for breast cancer risk among postmenopausal women.     

Dietary intake and risk of postmenopausal breast cancer (United States)

Objectives: While there is good evidence from cell-culture and animal studies to indicate that dietary intake impacts breast cancer risk, results of epidemiologic studies have been inconsistent. Additionally, while the etiology of breast cancer in premenopausal versus postmenopausal women may be quite different, most studies have not chosen to focus solely on one group or the other. In this case–control study, we evaluate the associations between red meat, fish, dairy products, and fruits and vegetables, and risk of breast cancer in postmenopausal women. Methods: A food-frequency questionnaire was completed by 441 women with in-situ or invasive breast cancer and 370 population controls. Cases were identified from the population-based Cancer Surveillance System (CSS) of western Washington and frequency age-matched controls identified by random-digit dialing (RDD). Unconditional logistic regression was used to model the association between each food grouping and breast cancer risk adjusting for age, number of pregnancies, and education. Results: Red meat intake was significantly associated with an increased breast cancer risk (p for trend = 0.002) and fish (including fried fish) and dairy product intake was inversely associated with breast cancer risk (p for trend = 0.04 and 0.05, respectively). No significant associations were noted between fruit or vegetable intake and breast cancer risk. Conclusions: The findings from this study support the results of several larger cohort studies and contribute to the evidence for the development of dietary recommendations for breast cancer risk reduction specific to postmenopausal women.     

Recreational physical activity and risk of postmenopausal breast cancer in a large cohort of US women

Due to its potential effects on ovarian hormone production, physical activity has been proposed as a modifiable risk factor for breast cancer. The authors analyzed data from the American Cancer Society Cancer Prevention Study II (CPS-II) Nutrition Cohort to examine the association between various measures of physical activity and postmenopausal breast cancer risk. Information on physical activity was obtained in 1992 via a self-administered questionnaire for 72,608 postmenopausal female participants who were cancer-free. During the five year prospective follow-up, 1520 incident breast cancer cases were identified among these women. Cox proportional hazards modeling was used to compute hazard rate ratios (RR) and to adjust for potential confounding factors including mammography. Women who were most physically active (>42.0 MET-h/week) at baseline had 29% lower incidence rates than active women with the least activity (>0–7.0 MET-h/week) (95% CI, 0.49–1.02). The difference in risk was largest for localized breast cancer, and for women who did not use hormone replacement therapy (HRT) at enrollment. Our findings are consistent with other studies that show lower risk of postmenopausal breast cancer associated with regular physical activity.     

Outdoor light at night and postmenopausal breast cancer risk in the NIH-AARP diet and health study

Circadian disruption may play a role in breast carcinogenesis. Previous studies reported relationships between outdoor light at night (LAN) and the breast cancer risk, but their findings are mixed. There is also a need to examine LAN and breast cancer incidence according to different individual and environmental characteristics to identify subpopulations at greater risk associated with LAN exposure. We studied residential outdoor LAN estimated from satellite imagery at baseline (1996) in relation to postmenopausal breast cancer incidence over ~16 years of follow-up in 186 981 postmenopausal women including 12 318 incident postmenopausal breast cancer cases in the NIH-AARP Diet and Health Study. We used Cox proportional hazards models to estimate hazard ratios (HR) and two-sided 95% confidence intervals (CI) of the relationship between quintiles of LAN and postmenopausal breast cancer risk, overall and by hormone receptor status and cancer stage. We found that when compared to women in the lowest quintile of baseline LAN, those in the highest quintile had a 10% increase in postmenopausal breast cancer risk (HR (95% CI), 1.10 (1.02, 1.18), P-trend, .002). The association appeared to be stronger for estrogen receptor (ER) positive breast cancer (1.12 [1.02, 1.24], .007) than for ER-negative cancer (1.07 [0.85, 1.34], .66). Our findings also suggested that the relationship between LAN and breast cancer risk may differ by individual characteristics, such as smoking, alcohol drinking, sleep duration and BMI, and neighborhood environment. In conclusion, our study suggests that higher outdoor LAN exposure may be a risk factor for postmenopausal breast cancer.     

Serum enterolactone and postmenopausal breast cancer risk by estrogen, progesterone and herceptin 2 receptor status

Lignans are a group of estrogenic compounds present in plants. Several epidemiological studies proposed that lignans may protect against breast cancer by exerting anticarcinogenic activity. Levels of enterolactone were determined in serum samples of 1,250 cases and 2,164 controls from a large population-based case-control study. We assessed the association between serum enterolactone and postmenopausal breast cancer risk using conditional logistic regression accounting for potential risk and confounding factors. Fractional polynomials were used to determine the function that best fitted the data. Moreover, we assessed heterogeneity by estrogen/progesterone/herceptin (ER/PR/HER2) status of the tumor. Additionally, a meta-analysis with seven further studies addressing enterolactone concentrations and breast cancer risk was performed. Postmenopausal breast cancer risk decreased with increasing serum enterolactone levels [highest compared to lowest quintile: [odds ratio = 0.65; 95% confidence interval (CI) 0.52-0.83, p(trend) = < 0.0001]. A significant inverse association for ER+/PR+ as well as ER-/PR- tumors was observed, with a significantly stronger association for ER-/PR- tumors (p(heterogeneity) = 0.03). The association for ER-/PR- tumors did not differ by expression of HER2 (p(heterogeneity) = 0.3). The meta-analysis yielded a significant reduced pooled risk estimate of: 0.66; 95% CI: 0.55-0.77) comparing the highest to the lowest quantiles of enterolactone levels. We found strong evidence for a significant inverse association between serum enterolactone and postmenopausal breast cancer risk, which was stronger for ER-PR- than for ER+PR+ tumors but not differential by further expression of HER2. The overall evidence together with other studies supports an inverse association between higher serum enterolactone levels and postmenopausal breast cancer risk.     

Alcohol intake,drinking patterns and risk of postmenopausal breast cancer in Denmark: a prospective cohort study

Objective: The available epidemiological evidence indicates that drinking alcohol per se is associated with breast cancer. However, it has not been investigated how the breast cancer risk for a given total alcohol consumption depends on the drinking frequency. Methods: Within the prospective study on Diet, Cancer and Health, we examined the relationship between breast cancer, intake of total alcohol and frequency of drinking among 23,778 postmenopausal women, among whom 425 cases of breast cancer accrued during a median follow-up of 4.8 years. Results: The dose–response relationship between total alcohol intake and breast cancer showed an increase in the rate ratio of 1.10 per 10 g/day (95% CI: 1.04–1.16) with no evidence for differences by type of alcohol beverage. No interaction was found between drinking frequency and total alcohol intake in the risk of breast cancer (p = 0.40). Conclusions: The present study supports previous ones in showing a monotonic increase in the risk of breast cancer among postmenopausal women with increasing average daily intake of alcohol, and this relationship with alcohol intake did not depend on drinking frequency.     

Predicted basal metabolic rate and cancer risk in the European Prospective Investigation into Cancer and Nutrition

Emerging evidence suggests that a metabolic profile associated with obesity may be a more relevant risk factor for some cancers than adiposity per se. Basal metabolic rate (BMR) is an indicator of overall body metabolism and may be a proxy for the impact of a specific metabolic profile on cancer risk. Therefore, we investigated the association of predicted BMR with incidence of 13 obesity-related cancers in the European Prospective Investigation into Cancer and Nutrition (EPIC). BMR at baseline was calculated using the WHO/FAO/UNU equations and the relationships between BMR and cancer risk were investigated using multivariable Cox proportional hazards regression models. A total of 141,295 men and 317,613 women, with a mean follow-up of 14 years were included in the analysis. Overall, higher BMR was associated with a greater risk for most cancers that have been linked with obesity. However, among normal weight participants, higher BMR was associated with elevated risks of esophageal adenocarcinoma (hazard ratio per 1-standard deviation change in BMR [HR_1-SD]: 2.46; 95% CI 1.20; 5.03) and distal colon cancer (HR_1-SD: 1.33; 95% CI 1.001; 1.77) among men and with proximal colon (HR_1-SD: 1.16; 95% CI 1.01; 1.35), pancreatic (HR_1-SD: 1.37; 95% CI 1.13; 1.66), thyroid (HR_1-SD: 1.65; 95% CI 1.33; 2.05), postmenopausal breast (HR_1-SD: 1.17; 95% CI 1.11; 1.22) and endometrial (HR_1-SD: 1.20; 95% CI 1.03; 1.40) cancers in women. These results indicate that higher BMR may be an indicator of a metabolic phenotype associated with risk of certain cancer types, and may be a useful predictor of cancer risk independent of body fatness.     

A single-centre chart review exploring the adjusted association between breast cancer phenotype and prognosis

Purpose and Methods

Using a retrospective chart review, we investigated the differences in survival and prognostic factors between patients with triple-negative breast cancer (tnbc) and those with non-tnbc. The review included 1018 breast cancer patients who were diagnosed between 2000 and 2005 in Essex, Kent, and Lambton counties in Ontario, Canada.

Results

Our findings indicate that, although the unadjusted results suggested that patients with tnbc were more likely than patients with non-tnbc to die [hazard ratio (hr): 2.29; 95% confidence interval (ci): 1.33 to 2.93], an adjusted survival analysis revealed no significant difference in overall survival between the groups (hr: 1.22; 95% ci: 0.63 to 2.39). The significant predictors of survival in the adjusted analysis were age, stage of cancer, and size of cancer.

Conclusions

Our findings support those of earlier reports, which suggest that presenting tumour size is the most important prognostic factor in tnbc. Investigations into unique screening methods to identify these tumours at an earlier stage and to prevent advanced-stage cancer in this patient subpopulation are necessary.     

The association between stressful life events and breast cancer risk: a meta-analysis

Breast cancer is the most prevalent cancer in women in Western societies. Studies examining the relationship between stressful life events and breast cancer risk have produced conflicting results. The purpose of this meta-analysis was to identify studies on this relationship, between 1966 and December 2002, to summarize and quantify the association and to explain the inconsistency in previous results. Summary odds ratios and standard errors were calculated, using random effect meta-regression analyses, for the following categories: stressful life events, death of spouse, death of relative or friend, personal health difficulties, nonpersonal health difficulties, change in marital status, change in financial status and change in environmental status. The presence of publication bias has been explored, and sensitivity analyses were performed to identify heterogeneity, using calculation of the percentage of variability due to heterogeneity, meta-regression analyses and stratification. Only the categories stressful life events (OR = 1.77, 95% CI 1.31-2.40), death of spouse (OR = 1.37, 95% CI 1.10-1.71) and death of relative or friend (OR = 1.35, 95% CI 1.09-1.68) showed a statistically significant effect. Publication bias was identified in both stressful life events (p = 0.00) and death of relative or friend (p = 0.02). Sensitivity analyses resulted in the identification of heterogeneity in all categories, except death of spouse. The results of this meta-analysis do not support an overall association between stressful life events and breast cancer risk. Only a modest association could be identified between death of spouse and breast cancer risk.     

Effect of family history,obesity and exercise on breast cancer risk among postmenopausal women

We examined effects of obesity and lifetime exercise patterns on postmenopausal breast cancer risk according to family history in a large population-based case control study conducted in Los Angeles County, California, because we hypothesized that both factors would affect risk through similar mechanistic pathways, and that their effects would be stronger among women with a family history. We studied 1883 postmenopausal breast cancer case subjects and 1628 postmenopausal control subjects ranging in age from 55-72 years. Cases were diagnosed with incident breast cancer in the late 1980s and 1990s. Controls were individually matched to case subjects on age, ethnic origin and neighborhood. In-person interviews determined known breast cancer risk factors including: height, weight, lifetime exercise, and family history of breast and other cancers. Breast cancer risk was raised among women who had at least 1 first-degree relative with breast cancer (odds ratio [OR] = 1.68; 95% confidence interval [CI] = 1.36-2.08). Risk increased with increasing levels of body-mass index (wt-kg/ht-m(2)) (p-trend = 0.005). Breast cancer risk was reduced among women who maintained, on average, 17.6 metabolic equivalent of energy expenditure (MET)-hr of activity/week from menarche onward (OR = 0.66; 95% CI = 0.48-0.90). Body-mass index, adjusted for lifetime exercise, was strongly associated with breast cancer risk among women with a positive family history of breast cancer (p-trend < 0.0001), but only weakly associated among women with no family history (p-trend = 0.08; homogeneity of trends p = 0.0005). In contrast, the risk reduction associated with exercise activity, adjusting for body-mass index, was limited to women without a family history of breast cancer (p-trend = 0.001; homogeneity of trends p = 0.005). Body-mass index and exercise activity, both modifiable risk factors for breast cancer, seem to have differential effects depending on a woman's family history of breast cancer, and may impact risk through different biological mechanisms.     

The modifying effect of C-reactive protein gene polymorphisms on the association between central obesity and endometrial cancer risk

BACKGROUND.

Obesity is a major risk factor for endometrial cancer. Obesity, particularly central obesity, is considered as a systemic inflammatory condition and is related strongly to insulin resistance. C‐reactive protein (CRP) is the most recognized biologic marker of chronic systematic inflammation, and it is conceivable that the CRP gene may work together with obesity in the development of endometrial cancer.

METHODS.

On the basis of a population‐based case–control study in a Chinese population, the authors obtained obesity measurements and data on 6 CRP single‐nucleotide polymorphisms (SNPs) from 1046 patients with newly diagnosed endometrial cancer (cases) and from 1035 age frequency‐matched controls. The association of the CRP SNPs with endometrial cancer risk and their modification on the association between obesity and endometrial cancer risk were evaluated.

RESULTS.

Although CRP SNPs alone were not associated with endometrial cancer, the associations of endometrial cancer with central obesity, measured as the waist‐to‐hip ratio (WHR) and the waist circumference, seemed to be stronger in women who were homozygous for the major allele of reference SNP (rs)1130864 (cytidine [C]/C) than in women who had the C/thymidine (T) and T/T genotypes (interaction test: P = .013 for WHR; P = .083 for waist circumference). When the women were stratified further by menopausal status, the observed interactions persisted mainly in premenopausal women (interaction test: P < .001 for WHR; P = .002 for waist circumference).

CONCLUSIONS.

The current results suggested that, in the Chinese population that was studied, obesity‐related insulin resistance and proinflammatory effects may play an important role in endometrial cancer risk, and these effects were modified significantly by the CRP SNP rs1130864. Cancer 2008. © 2008 American Cancer Society.     

Associations between obesity,metabolic health,and the risk of breast cancer in East Asian women

Background This study examined the associations between metabolic syndrome(MetS), obesity, their combination as a metabolic obesity phenotype, and the risk of breast cancer in East Asian postmenopausal women.Methods A total of 3,095,336 postmenopausal cancer-free women aged 40–79 years who underwent the National Health Insurance Service health examination between 2009 and 2010 were included. The incidence of invasive breast cancer was followed up until 2018. The presence of obesity (body mass index[BMI] ≥25 kg/m²), MetS, and each component of MetS was investigated.Results Obesity and MetS were associated with breast cancer risk, but when the effects of obesity and MetS were mutually adjusted, the associations were attenuated, especially for MetS. Only elevated fasting blood glucose levels and waist circumference increased the risk of breast cancer after adjusting for BMI. Compared to metabolically healthy normal-weight women, metabolically unhealthy normal-weight women, metabolically healthy obese, and metabolically unhealthy obese women had an increased risk of breast cancer.Conclusions Obesity and MetS were independently associated with an increased risk of breast cancer in postmenopausal women, despite the relationship between MetS and breast cancer appearing to result from a partial association with BMI. Postmenopausal women should be encouraged to control their weight and metabolic health.Subject terms: Risk factors, Weight management