Obesity and the outcome of young breast cancer patients in the UK: the POSH study

Copson, Ellen; Cutress, Ramsey I.; Maishman, Tom; Eccles, Bryony; Gerty, Sue; Stanton, Louise; Altman, Douglas G.; Durcan, Lorraine; Wong, C.Y.Y.; Simmonds, Peter; Jones, Louise; Eccles, Diana M.

doi:10.1093/annonc/mdu509

Cited by 83 publications

(82 citation statements)

References 24 publications

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“…Several clinical trials have demonstrated that obesity at diagnosis is associated with breast-cancer-specific survival (BCSS) and a1111111111 a1111111111 a1111111111 a1111111111 a1111111111 overall survival (OS) [1][2][3], which was additionally supported by recent meta-analyses [4]. However, other studies have found no association between BMI and the prognosis of breast cancer [5][6][7].…”

Section: Introductionmentioning

confidence: 93%

Interaction between body mass index and hormone-receptor status as a prognostic factor in lymph-node-positive breast cancer

Chung¹,

Lee²,

Lee³

et al. 2017

The Breast

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The aim of this study was to determine the relationship between the body mass index (BMI) at a breast cancer diagnosis and various factors including the hormone-receptor, menopause, and lymph-node status, and identify if there is a specific patient subgroup for which the BMI has an effect on the breast cancer prognosis. We retrospectively analyzed the data of 8,742 patients with non-metastatic invasive breast cancer from the research database of Asan Medical Center. The overall survival (OS) and breast-cancer-specific survival (BCSS) outcomes were compared among BMI groups using the Kaplan-Meier method and Cox proportional-hazards regression models with an interaction term. There was a significant interaction between BMI and hormone-receptor status for the OS (P = 0.029), and BCSS (P = 0.013) in lymph-node-positive breast cancers. Obesity in hormone-receptor-positive breast cancer showed a poorer OS (adjusted hazard ratio [HR] = 1.51, 95% confidence interval [CI] = 0.92 to 2.48) and significantly poorer BCSS (HR = 1.80, 95% CI = 1.08 to 2.99). In contrast, a high BMI in hormone-receptor-negative breast cancer revealed a better OS (HR = 0.44, 95% CI = 0.16 to 1.19) and BCSS (HR = 0.53, 95% CI = 0.19 to 1.44). Being underweight (BMI < 18.50 kg/m 2 ) with hormone-receptor-negative breast cancer was associated with a significantly worse OS (HR = 1.98, 95% CI = 1.00-3.95) and BCSS (HR = 2.24, 95% CI = 1.12-4.47). There was no significant interaction found between the BMI and hormonereceptor status in the lymph-node-negative setting, and BMI did not interact with the menopause status in any subgroup. In conclusion, BMI interacts with the hormone-receptor status in a lymph-node-positive setting, thereby playing a role in the prognosis of breast cancer.

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Section: Introductionmentioning

confidence: 93%

Interaction between body mass index and hormone-receptor status as a prognostic factor in lymph-node-positive breast cancer

Chung¹,

Lee²,

Lee³

et al. 2017

The Breast

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“…In clinical condition, the association between obesity and HER2-overexpressing breast cancer is perplexing [148], [149], [150]. Nonetheless, Tan et al [151] recorded that the fat mass and obesity-associated (FTO) gene expression in the HER2-overexpressed subtype of breast cancer was significantly higher.…”

Section: Clinical Studies On Breast Cancer and Her2 With Reference Tomentioning

confidence: 99%

Tumor-linked HER2 expression: association with obesity and lipid-related microenvironment

Ray

2017

Hormone Molecular Biology and Clinical Investigation

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Abstract:Obesity is associated with the risk of several health disorders including certain cancers. Among obesity-related cancers, postmenopausal breast carcinoma is a well-studied one. Apart from an increase in certain types of lipids in obesity, excess adipose tissue releases many hormone-like cytokines/adipokines, which are usually pro-inflammatory in nature. Leptin is one of such adipokines and significantly linked with the intracellular signaling pathways of other growth factors such as insulin-like growth factor-1 (IGF-1), vascular endothelial growth factor (VEGF), human epidermal growth factor receptor 2 (HER2). In general, HER2 is overexpressed in roughly 30% of breast carcinomas; its presence indicates aggressive tumor behavior. Conversely, HER2 has certain effects in normal conditions such as differentiation of preadipocytes, cardiovascular health and vitamin D metabolism. HER2 has no known endogenous ligand, but it may form dimers with other three members of the epidermal growth factor receptor (EGFR) family and can activate downstream signaling pathways. Furthermore, HER2 is intimately connected with several enzymes, e.g. fatty acid synthase (FASN), phosphatidylinositol 3-kinase (PI3K), AKT and mechanistic target of rapamycin (mTOR), all of which play significant regulatory roles in lipogenic pathways or lipid metabolism. In obesity-related carcinogenesis, characteristics like insulin resistance and elevated IGF-1 are commonly observed. Both IGF-1 and leptin can modulate EGFR and HER2 signaling pathways. Although clinical studies have shown mixed results, the behavior of HER2+ tumor cells including HER2 levels can be altered by several factors such as obesity, leptin and fatty acids. A precise knowledge is useful in new therapeutic approaches against HER+ tumors.

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“…On the contrary, fat tissue shows increased levels of leptin, resulting in low TGF‐β and IL‐10 levels. However, obese breast cancer patients still have higher mortality, which may be a result of the association between obesity and increased tumor size, positive lymph node involvement, and triple‐negative subtype, but not the secretion of TGF‐β and IL‐10 . Other nutritional parameters were not significantly associated with levels of TGF‐β, IL‐10 and Foxp3, potentially because there is a nondirect correlation between them in terms of biological mechanism.…”

Section: Discussionmentioning

confidence: 94%

Low BMI is correlated with increased TGF‐β and IL‐10 mRNA levels in the peripheral blood of breast cancer patients

et al. 2018

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Transforming growth factor-β (TGF-β), interleukin-10 (IL-10), and forkhead box P3 (Foxp3) have important roles in breast cancer development. Previous studies confirmed a correlation between these immune molecules and tumor characteristics, but their association with nutritional status in breast cancer is largely unknown. We aimed to investigate the association between body mass index (BMI), hemoglobin, total protein, albumin, globulin (GLB), albumin/GLB ratio (AGR), pre-albumin, prognostic nutritional index, and TGF-β, IL-10, and Foxp3 mRNA expression in patients with breast cancer. Quantitative real-time PCR was used to detect the mRNA expression of TGF-β, IL-10, and Foxp3 in the peripheral blood of 107 patients with breast cancer and 21 healthy controls. We found that TGF-β mRNA levels were 2.6-fold, 3.2-fold, and 2.3-fold higher in patients with low BMI (<23), low AGR, and high GLB, respectively, than in their counterparts (P < 0.05). In addition, IL-10 mRNA expression levels in patients with normal BMI (<23) were 2.8-fold and 3.5-fold higher than in those who were overweight (23≤ BMI <25) and obese (BMI ≥ 25), respectively (P < 0.05). In addition, TGF-β, IL-10, and Foxp3 mRNA levels were significantly higher in patients with breast cancer than in healthy controls (P < 0.05). In summary, our results suggest that nutritional status, especially BMI, may strongly affect systematic immune function in patients with breast cancer. © 2018 IUBMB Life, 70(3):237-245, 2018.

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Obesity and the outcome of young breast cancer patients in the UK: the POSH study

Abstract: Young obese breast cancer patients present with adverse tumour characteristics. Despite adjustment for this, obesity still independently predicts DDFI and OS.

Cited by 83 publications

References 24 publications

Interaction between body mass index and hormone-receptor status as a prognostic factor in lymph-node-positive breast cancer

Interaction between body mass index and hormone-receptor status as a prognostic factor in lymph-node-positive breast cancer

Tumor-linked HER2 expression: association with obesity and lipid-related microenvironment

Low BMI is correlated with increased TGF‐β and IL‐10 mRNA levels in the peripheral blood of breast cancer patients

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