Obesity and Triple-Negative Breast Cancer

Dietze, Eric C.; Chavez, Tanya A.; Seewaldt, Victoria L.

doi:10.1016/j.ajpath.2017.09.018

Cited by 89 publications

(64 citation statements)

References 98 publications

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“…Over the past 20 years there has been a significant increase worldwide in obesity, type-2 diabetes, and gestational diabetes (59). Contributors include adoption of a Western diet, high in calories and low in nutritionals (1), lack of access to healthy foods (https:// www.ncbi.nlm.nih.gov/pubmed/25032337) (2), and adoption of a sedentary lifestyle.…”

Section: Obesity Epidemicmentioning

confidence: 99%

“…Furthermore, the relationship between BMI and adiposity varies significantly between different races and ethnic groups. The relationship(s) between body shape/composition and disease is an inexact science and only beginning to be understood (59,169,170). It is well-recognized, however, that African-Americans/Blacks have higher muscle mass than non-Hispanic Whites and Asians (59).…”

Section: Bmi-an Inexact Measurementioning

confidence: 99%

“…There is a second problem with using BMI as a surrogate measure for metabolic health. The BMI threshold for type-2 diabetes risk markedly varies in individuals of different races and ethnicities (59). In a large multiethnic cohort study, for an equivalent incidence rate of type-2 diabetes conferred by a BMI of 30 kg/m 2 in non-Hispanic Whites, the BMI was found to be 26 kg/m 2 in African-Americans/Blacks, 25 kg/m 2 in Chinese-Americans, and 24 kg/m 2 in South Asians (171,172).…”

Section: Bmi-an Inexact Measurementioning

confidence: 99%

“…Peripheral muscle tissue is the major determinant of insulinsensitivity; this is why exercise is thought to have such a key impact on improving insulin-sensitivity and metabolic health in insulin resistant individuals. It is known that that African-Americans/Blacks have lower insulin sensitivity of their peripheral muscles than non-Hispanic White women (59,180). Lower peripheral insulin sensitivity in African-American/Black women compared to non-Hispanic White women could account for these differences and, thus, make is difficult to determine "metabolically healthy" BMI cut off points (172).…”

Section: Racial and Ethnic Differences In Insulin-sensitivitymentioning

confidence: 99%

“…TNBCs are ER-/PR-and HER2-not amplified. TNBC occur most frequently in BRCA1 mutation carriers and young African-American/Black women and frequently carry a poor prognosis (59). Basal-type breast cancers are a subtype of TNBC that are identified by specific gene expression patterning (59).…”

Section: Pi3k/akt/mtormentioning

confidence: 99%

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Metabolic Health, Insulin, and Breast Cancer: Why Oncologists Should Care About Insulin

Yee¹,

Mortimer²,

Natarajan³

et al. 2020

Front. Endocrinol.

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The potential association between obesity and TNBC has been a subject of intense research study. As outlined below, studies investigating the potential relationship between obesity and TNBC have been inconsistent. This is a summary of some of the key studies that have been recently published.The Carolina Breast Cancer Study is a North Carolina population-based case-controlled study of breast cancer, conducted in three phases (28). The current study phase, Phase 3 (years 2008-2014), includes women resident in 44 North Carolina Counties (28), employing randomized recruitment to oversample African-American/Black women and women under age 50 (28). Waist to hip ratio (WHR) was compared between the highest (≥0.84) and lowest (<0.77) groups vs. the basal-type subset of TNBC. There was an increased risk [odds ratio (OR) = 2.3; 95% CI, 1.4-3.6] for basal-type TNBC in women with higher WHR (43). Premenopausal women (OR = 1.8; 95% CI, 1.0-3.4) and post-menopausal women (OR = 2.7; 95% CI, 1.3-5.4) with the highest WHR had increased risk of developing basal-type TNBC compared to the lowest WHR (43). Basal-type breast cancer was observed to be highest among premenopausal African-American/Black women (43). There was no significant association between increased BMI (defined as BMI ≥ 25 kg/m 2 ) and basal-type TNBC.The Appalachian Study investigated the potential association between obesity (defined as BMI ≥ 30 kg/m 2 ) and TNBC in 620 predominantly non-Hispanic White women in rural Appalachia. This study reported a significant association between obesity and the incidence of TNBC (29).Women's CARE study is a case-controlled study of BMI and breast cancer risk in non-Hispanic White women and African-American/Black women. The Women's CARE study reported (1) an inverse association between a woman's BMI at age 18 and premenopausal ER-/PR-breast cancer and (2) a positive association between current BMI and post-menopausal ER+/PR+ breast cancer (30).

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Section: Obesity Epidemicmentioning

confidence: 99%

Section: Bmi-an Inexact Measurementioning

confidence: 99%

Section: Bmi-an Inexact Measurementioning

confidence: 99%

Section: Racial and Ethnic Differences In Insulin-sensitivitymentioning

confidence: 99%

Section: Pi3k/akt/mtormentioning

confidence: 99%

See 3 more Smart Citations

Metabolic Health, Insulin, and Breast Cancer: Why Oncologists Should Care About Insulin

Yee¹,

Mortimer²,

Natarajan³

et al. 2020

Front. Endocrinol.

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Prevalence, Consequences, Causes and Management of Obesity

Tappia

Defries

2020

Pathophysiology of Obesity-Induced Health Complications

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Molecular mechanisms linking high body mass index to breast cancer etiology in post-menopausal breast tumor and tumor-adjacent tissues

Heng

Wang

Ahearn

et al. 2018

Breast Cancer Res Treat

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Purpose: In postmenopausal women, high body mass index (BMI) is an established breast cancer risk factor and is associated with worse breast cancer prognosis. We assessed the associations between BMI and gene expression of both breast tumor and adjacent tissue in estrogen receptor positive (ER+) and negative (ER-) diseases to help elucidate the mechanisms linking obesity with breast cancer biology in 519 postmenopausal women from the Nurses' Health Study (NHS) and NHSII.Methods: Differential gene expression was analyzed separately in ER+ and ER-disease both comparing overweight (BMI ≥25 to <30) or obese (BMI ≥30) women to women with normal BMI (BMI <25), and per 5 kg/m 2 increase in BMI. Analyses controlled for age and year of diagnosis, physical activity, alcohol consumption and hormone therapy use. Gene set enrichment analyses were performed and validated among a subset of postmenopausal cases in The Cancer Genome Atlas (for tumor) and Polish Breast Cancer Study (for tumor-adjacent). Results:No gene was differentially expressed by BMI (FDR<0.05). BMI was significantly associated with increased cellular proliferation pathways, particularly in ER+ tumors, and increased inflammation pathways in ER-tumor and ER-tumor-adjacent tissues (FDR<0.05). High BMI was associated with upregulation of genes involved in epithelial mesenchymal transition in ER+ tumor-adjacent tissues. Conclusions:This study provides insights into molecular mechanisms of BMI influencing postmenopausal breast cancer biology. Tumor and tumor-adjacent tissues provide independent information about potential mechanisms.

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Obesity and Triple-Negative Breast Cancer

Cited by 89 publications

References 98 publications

Metabolic Health, Insulin, and Breast Cancer: Why Oncologists Should Care About Insulin

Metabolic Health, Insulin, and Breast Cancer: Why Oncologists Should Care About Insulin

Prevalence, Consequences, Causes and Management of Obesity

Molecular mechanisms linking high body mass index to breast cancer etiology in post-menopausal breast tumor and tumor-adjacent tissues

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