High BMI has been repeatedly identified as a risk factor for breast cancer (BC), but also as an adverse prognostic factor in women with early-stage BC. Little is known about its impact on outcome in ...patients with metastatic BC (MBC).
We used the National ESME-MBC cohort, which includes all consecutive patients (pts) newly diagnosed with MBC between Jan 2008 and Dec 2016 in 18 French comprehensive cancer centres. Women with available BMI at the diagnosis of MBC were selected. Four groups were defined according to WHO classification: underweight (BMI < 18.5kg/m2), normal weight (18.5-24.9), overweight (25.0-29.9) and obese (≥30.0). Multivariate Cox analyses for OS were conducted in the whole population (primary objective). OS and 1st line progression-free survival (PFS) in subtypes (HER2+, Triple negative BC (TNBC) and HR+ HER2-) were secondary objectives.
Of 22 463 patients in the ESME cohort, 12 999 women had BMI data available. Med BMI was 24.9kg/m2 (range 12.1-66.5). Pts characteristics are reported in Table. Obesity was associated with more de novo MBC, while underweight pts had more aggressive features. Median follow-up was 48.6 months. Median OS was 47.4 months (95% CI 46.2-48.5). By multivariate analysis, age, visceral metastases, time to MBC, number of metastatic sites, tumor subtype and BMI were independent predictors for OS. Underweight (but not overweight or obesity) was associated with a worse prognosis (HR 1.29, 95%CI 1.16-1.44), and this was true in each tumour subtype. Median 1st line PFS was 12.2 months, with similar multivariate results.Table367PTableUnderweightNormal weightOverweightObesepN637 (5%)6020 (46%)3708 (29%)2634 (20%)Age at MBC diagnosis (med)58586160<0.001De novo MBC228 (36%)1939 (32%)1389 (37%)1132 (43%)0.000Time to MBC (med, months)24332718<0.001Visceral metastases400 (63%)3543 (59%)2148 (58%)1484 (56%)0.012Subtype HR+HER2-354 (56%)3566 (59%)2311 (62%)1633 (62%)0.000HER2+131 (21%)1295 (21%)725 (20%)545 (21%)TNBC105 (16%)860 (14%)499 (13%)345 (13%)>3 metastatic sites180 (28%)1306 (22%)753 (20%)553 (21%)0.000Median OS (95% CI)33 (29-40)47 (45-49)49 (47-51)48 (45-51)
Unlike in early-stage BC, overweight and obesity do not seem associated with poorer OS in MBC women, whatever the subtype, on the opposite of underweight.
The authors.
Has not received any funding.
M. Robain: Research grant / Funding (institution), ESME plateform support: Roche; Research grant / Funding (institution), ESME plateform support: AstraZeneca; Research grant / Funding (institution), ESME plateform support: Pfizer; Research grant / Funding (institution), ESME plateform support: BMS; Research grant / Funding (institution), ESME plateform support: DAIICHI Sankyo. All other authors have declared no conflicts of interest.
Magnetic resonance imaging (MRI) is a method of choice for follow-up of irradiated brain metastasis. It is difficult to differentiate local tumour recurrences from radiation induced-changes in case ...of suspicious contrast enhancement. New advanced MRI techniques (perfusion and spectrometry) and amino acid positron-emission tomography (PET) allow to be more accurate and could avoid a stereotactic biopsy for histological assessment, the only reliable but invasive method. We report the case of a patient who underwent surgery for a single, left frontal brain metastasis of a breast carcinoma, followed by adjuvant stereotactic radiotherapy in the operative bed. Seven months after, she presented a local change in the irradiated area on the perfusion-weighted MRI, for which the differentiation between a local tumour recurrence and radionecrosis was not possible. PET with 2-deoxy-((18)F)-fluoro-D-glucose (FDG) revealed a hypermetabolic lesion. After surgical resection, the histological assessment has mainly recovered radionecrosis with few carcinoma cells. The multimodal MRI has greatly contributed to refine the differential diagnosis between tumour recurrence and radionecrosis, which remains difficult. The FDG PET is helpful, in favour of the diagnosis of local tumour recurrence when a hypermetabolic lesion is found. Others tracers (such as carbon 11 or a fluoride isotope) deserve interest but are not available in all centres. Stereotactic biopsy should be discussed if any doubt remains.
Inflammation is now recognized as a major factor contributing to type 2 diabetes (T2D). However, while the mechanisms and consequences associated with white adipose tissue inflammation are well ...described, very little is known concerning the situation in skeletal muscle. The aim of this study was to investigate, in vitro and in vivo, how skeletal muscle inflammation develops and how in turn it modulates local and systemic insulin sensitivity in different mice models of T2D and in humans, focusing on the role of the chemokine MCP1. Here, we found that skeletal muscle inflammation and macrophage markers are increased and associated with insulin resistance in mice models and humans. In addition, we demonstrated that intra-muscular TNFα expression is exclusively restricted to the population of intramuscular leukocytes and that the chemokine MCP1 was associated with skeletal muscle inflammatory markers in these models. Furthermore, we demonstrated that exposure of C2C12 myotubes to palmitate elevated the production of the chemokine MCP1 and that the muscle-specific overexpression of MCP1 in transgenic mice induced the local recruitment of macrophages and altered local insulin sensitivity. Overall our study demonstrates that skeletal muscle inflammation is clearly increased in the context of T2D in each one of the models we investigated, which is likely consecutive to the lipotoxic environment generated by peripheral insulin resistance, further increasing MCP1 expression in muscle. Consequently, our results suggest that MCP1-mediated skeletal muscle macrophages recruitment plays a role in the etiology of T2D.
Inflammation is now recognized as a major factor contributing to type 2 diabetes (T2D). However, while the mechanisms and consequences associated with white adipose tissue inflammation are well ...described, very little is known concerning the situation in skeletal muscle. The aim of this study was to investigate, in vitro and in vivo, how skeletal muscle inflammation develops and how in turn it modulates local and systemic insulin sensitivity in different mice models of T2D and in humans, focusing on the role of the chemokine MCP1. Here, we found that skeletal muscle inflammation and macrophage markers are increased and associated with insulin resistance in mice models and humans. In addition, we demonstrated that intra-muscular TNFα expression is exclusively restricted to the population of intramuscular leukocytes and that the chemokine MCP1 was associated with skeletal muscle inflammatory markers in these models. Furthermore, we demonstrated that exposure of C2C12 myotubes to palmitate elevated the production of the chemokine MCP1 and that the muscle-specific overexpression of MCP1 in transgenic mice induced the local recruitment of macrophages and altered local insulin sensitivity. Overall our study demonstrates that skeletal muscle inflammation is clearly increased in the context of T2D in each one of the models we investigated, which is likely consecutive to the lipotoxic environment generated by peripheral insulin resistance, further increasing MCP1 expression in muscle. Consequently, our results suggest that MCP1-mediated skeletal muscle macrophages recruitment plays a role in the etiology of T2D.
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