The association between metabolic health, obesity phenotype and the risk of breast cancer

Park, Young Jun; White, Alexandra J.; Nichols, Hazel B.; O’Brien, Katie M.; Weinberg, Clarice R.; Sandler, Dale P.

doi:10.1002/ijc.30684

Cited by 93 publications

(109 citation statements)

References 55 publications

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“…In our study, BMI of ≥30 kg/m 2 was associated with higher risks of both ILC and IDC, although the association was stronger for ILC. Obesity is an established risk factor for postmenopausal breast cancer; however, the association with different subtypes of breast cancer remains unclear . In the present study, we did not observe any significant difference in the association between BMI and risk of the two breast cancer subtypes, which is in agreement with previous reports .…”

Section: Discussionsupporting

confidence: 93%

Heterogeneity in risk factors for ductal and lobular breast carcinomas: A case–control study

Dianatinasab

Fararouei

Daneshi³

et al. 2019

Intl Journal of Cancer

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Invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) of the breast are the most common histological subtypes of breast cancer. However, the associations and heterogeneity between histological subtypes and their risk factors are not well established. This study aimed to investigate risk factors for IDC and ILC. This case-control study included 1,009 incident breast cancer cases and 1,009 hospital controls, frequency-matched by age. Data were obtained from the patients' medical files and an interview administered via a questionnaire. Multinomial logistic regression was used and odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. The heterogeneity of the associations was assessed using the Wald test. Family history of breast cancer was associated with IDC (OR 2.64, 95% CI: 1.97-3.55) but not ILC (OR 0.81, 95% CI: 0.42-1.57; p for heterogeneity <0.001). Conversely, a history of miscarriage was associated with ILC (OR 1.71, 95% CI: 1.17-2.51) but not IDC (OR 1.18, 95% CI: 0.95-1.46; p for heterogeneity = 0.04). Similarly, type 2 diabetes was associated with ILC but not IDC (p for heterogeneity = 0.02). Age at first delivery and breastfeeding were significantly associated with IDC but not ILC, though p values for heterogeneity did not reach the significance level. Deliberate weight loss and age at menarche were significantly associated with ILC but not IDC (p for heterogeneity ≥0.27). Smoking, history of benign breast disease and BMI were associated with both subtypes. The present study supports the hypothesis that IDC and ILC are etiologically distinct tumours. Cancer Epidemiologyheterogeneity of ductal and lobular breast carcinomas risk factors Int. J. Cancer: 145, 2917-2925 (2019) © 2019 UICC Cancer Epidemiology heterogeneity of ductal and lobular breast carcinomas risk factors Int.

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Section: Discussionsupporting

confidence: 93%

Heterogeneity in risk factors for ductal and lobular breast carcinomas: A case–control study

Dianatinasab

Fararouei

Daneshi³

et al. 2019

Intl Journal of Cancer

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“…Obesity was a risk factor for incident gastric cancer [3], although the effect of obesity on gastric cancer was smaller than that on other obesity-related cancers. Previous studies revealed that the risk of incident colorectal cancer [12] and incident breast cancer [13], both of which have been shown to be related to obesity [4], was not high in subjects with MHO. In addition, another study revealed that the risk of obesity-related cancer in MHO was lower than that in MAO [32].…”

Section: Discussionmentioning

confidence: 96%

“…However, these studies also revealed that individuals with the MHO phenotype were at higher risk of T2DM, CKD and CVD than individuals with metabolically healthy non-obese [8,10,11]. In addition, there is accumulating evidence that metabolically abnormal obesity (MAO), but not MHO, confers an elevated risk of incident colon cancer [12] and breast cancer [13]. The association between gastric cancer and obesity among Japanese population is controversial [14,15].…”

Section: Introductionmentioning

confidence: 99%

Impact of metabolically healthy obesity on the risk of incident gastric cancer: a population-based cohort study

et al. 2020

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Background: The risk of colon or breast cancer in metabolically healthy obese (MHO) were lower than that in metabolically abnormal obese (MAO). We hypothesized that the risk of incident gastric cancer in MHO is lower than that in MAO.Methods: This historical cohort study included 19,685 Japanese individuals who received health-checkup programs from 2003 to 2016. Each subject was classified as metabolically healthy (MH) (no metabolic abnormalities) or metabolically abnormal (MA) (one or more metabolic abnormalities), according to four metabolic factors (hypertension, impaired fasting glucose, hypertriglyceridemia and low HDL-cholesterol). Obese (O) or non-obese (NO) was classified by a BMI cutoff of 25.0 kg/m 2 . Hazard ratios of metabolic phenotypes for incident gastric cancer were calculated by the Cox proportional hazard model with adjustments for age, sex, alcohol consumption, smoking and exercise. Results: Over the median follow-up period of 5.5 (2.9-9.4) years, incident rate of gastric cancer was 0.65 per 1000 persons-years. Incident rate of MHNO, MHO, MANO and MAO were 0.33, 0.25, 0.80 and 1.21 per 1000 persons-years, respectively. Compared with MHNO, the adjusted hazard ratios for development of gastric cancer were 0.69 (95% CI 0.04-3.39, p = 0.723) in MHO, 1.16 (95% CI 0.63-2.12, p = 0.636) in MANO and 2.09 (95% CI 1.10-3.97, p = 0.024) in MAO.Conclusions: This study shows that individuals with MAO, but not those with MHO, had an elevated risk for incident gastric cancer. Thus, we should focus more on the presence of metabolic abnormalities rather than obesity itself for incident gastric cancer.

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“…9 Similarly, in the Sister Study, normal-weight women with at least one metabolic abnormality and women with BMI ≥ 25 kg/m 2 had a nearly equivalent increase in the risk of postmenopausal breast cancer compared to normal-weight women with no metabolic abnormalities. 43 Other studies, however, have yielded different results. Women in the Framingham Heart Study with BMI ≥ 25 kg/m 2 and elevated glucose levels had an increased risk of postmenopausal breast cancer, whereas normal-weight women with elevated glucose were not at increased risk, 44 while Kabat and colleagues found no difference in breast cancer risk between metabolically healthy versus metabolically unhealthy normal-weight participants in the WHI when using multiple criteria to define metabolic health.…”

Section: Discussionmentioning

confidence: 98%

Association of Body Fat and Risk of Breast Cancer in Postmenopausal Women With Normal Body Mass Index

et al. 2019

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Importance: Obesity is associated with increased risk of breast cancer, including the estrogen receptor (ER)-positive subtype in postmenopausal women. It is unknown whether excess adiposity is associated with increased risk in women with a normal body mass index (BMI). Objective: To investigate the association between body fat and breast cancer risk in normal BMI women. Design: This secondary analysis of the Women’s Health Initiative (WHI) cohort was restricted to participants with BMI 18.5 to <25.0 kg/m2. Setting: Women ages 50 to 79 years were enrolled from 1993 to 1998. Body fat was measured by dual energy X-ray absorptiometry (DXA) at 3 designated centers. Participants: 3,460 postmenopausal women with normal BMI who had DXA measures were included. At a median follow-up of 16 years, 182 incident breast cancers had been ascertained; 146 were ER-positive. Main Outcomes and Measures: DXA-derived body fat levels were measured at baseline and years 1, 3, 6, and 9. Information on demographic data, medical history, and lifestyle factors was collected at baseline. Invasive breast cancers were confirmed via central review of medical records by physician adjudicators. Blood analytes were measured in subsets of participants. Results: Multivariable-adjusted hazard ratios (HRs) for risk of invasive breast cancer were 1.89 (95% CI 1.21 to 2.95) and 1.88 (95% CI 1.18 to 2.98) in the uppermost versus lowest quartiles of whole body fat and trunk fat mass, respectively. The corresponding adjusted HRs for ER-positive breast cancer were 2.21 (95% CI 1.23 to 3.67) and 1.98 (95% CI 1.18 to 3.31), respectively. Similar positive associations were observed when accounting for serial DXA measurements in time-dependent covariate analyses for ER-positive breast cancer. Circulating insulin, C-reactive protein, interleukin-6, leptin and triglycerides were higher, while HDL-cholesterol and sex hormone binding globulin were lower in the uppermost versus lowest quartiles of trunk fat mass. Conclusions and Relevance: In normal BMI postmenopausal women, relatively high body fat was associated with elevated risk of invasive breast cancer and altered levels of circulating metabolic and inflammatory factors. Normal BMI categorization may be an inadequate proxy for the risk of breast cancer in postmenopausal women.

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The association between metabolic health, obesity phenotype and the risk of breast cancer

Cited by 93 publications

References 55 publications

Heterogeneity in risk factors for ductal and lobular breast carcinomas: A case–control study

Heterogeneity in risk factors for ductal and lobular breast carcinomas: A case–control study

Impact of metabolically healthy obesity on the risk of incident gastric cancer: a population-based cohort study

Association of Body Fat and Risk of Breast Cancer in Postmenopausal Women With Normal Body Mass Index

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