scholarly journals Estrogens and Glucocorticoids in Mammary Adipose Tissue: Relationships with Body Mass Index and Breast Cancer Features

2019 ◽  
Vol 105 (4) ◽  
pp. e1504-e1516 ◽  
Author(s):  
Sofia Laforest ◽  
Mélissa Pelletier ◽  
Nina Denver ◽  
Brigitte Poirier ◽  
Sébastien Nguyen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Body Mass Index ◽  
Adipose Tissue ◽  
Body Mass ◽  
Tumor Size ◽  
Breast Tumors ◽  
Partial Mastectomy ◽  
Negatively Associated ◽  
Breast Adipose Tissue ◽  
Breast Adipose

Abstract Context Adipose tissue is an important site for extragonadal steroid hormone biosynthesis through the expression and activity of P450 aromatase, 11β-hydroxysteroid dehydrogenase (HSD) 1, and 17β-HSDs. The contribution of steroid hormones produced by adjacent adipose tissue for the progression and survival of breast tumors is unknown. Objective To quantify estrogens (estradiol, estrone) and glucocorticoids (cortisol, cortisone) in breast adipose tissue from both healthy and diseased women and their relationships with adiposity indices and breast cancer prognostic markers. Design and setting Breast adipose tissue was collected at time of surgery. Patients Pre- and postmenopausal women undergoing partial mastectomy for treatment of breast cancer (n = 17) or reduction mammoplasty (n = 6) were studied. Interventions Relative estrogen and glucocorticoid amounts were determined by liquid chromatography tandem mass spectrometry. Results The targeted steroids were reliably detected and quantified in mammary adipose tissues. Women with ER+/PR+ tumor had higher relative estradiol amount than women with ER–/PR– tumor (P < .05). The ratio of estradiol-to-estrone was higher in lean women than in women with a body mass index (BMI) ≥ 25 kg/m2 (P < .05). Mixed-model analyses showed that estradiol, cortisone, and cortisol were negatively associated with tumor size (P < .05). Relationships between glucocorticoids and tumor size remained significant after adjustment for BMI. The cortisol-to-cortisone ratio was negatively associated with tumor stage (P < .05) independently of BMI. Conclusions We reliably quantified estrogens and glucocorticoids in breast adipose tissue from healthy women and women suffering from breast cancer. Our findings suggest that smaller breast tumors are associated with higher relative amounts of estradiol and cortisol in adipose tissue.

scholarly journals SAT-126 Breast Adipose Tissue Extracellular Vesicles from Obese Women Increase Breast Cancer Aggressiveness - a Novel Mechanism for the Obesity-Breast Cancer Link

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Alberto Benito-Martin ◽  
Paul Paik ◽  
Malik Mushannen ◽  
Priya Bhardwaj ◽  
Sonya Oshchepkova ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Body Mass Index ◽  
Adipose Tissue ◽  
Body Mass ◽  
Extracellular Vesicles ◽  
Human Breast ◽  
Mouse Xenograft Model ◽  
Breast Adipose Tissue ◽  
Breast Adipose

Abstract Background and Objectives: Breast cancer is among the most common cancer in women with 2.1 million new cases detected each year. Numerous studies have demonstrated a connection between body mass index (BMI) and cancer incidence, with obesity (BMI ≥ 30) being responsible for the development of at least 13 types of cancer, and 15% to 20% of total cancer-related mortality. The effects of extracellular vesicles (EVs) derived from the obese adipose tissue microenvironment on breast cancer have not yet been clearly elucidated. Methods: EVs were obtained from media conditioned with human breast adipose tissue from reduction mammoplasty (n=31). Women were healthy at the time of surgery and had no history of breast cancer. Patient samples were stratified based on their body mass index (BMI), with a BMI < 25 considered healthy and a BMI ≥ 25 considered overweight/obese. Breast adipose tissue-derived EVs (AT-EVs) were characterized (Quantitative Mass Spectrometry) and used to treat human breast cancer cell lines, including the ER+ MCF7 and triple negative breast cancer (TNBC) MDA-MB-231. Effects on cell proliferation and migration in vitro, and on tumor growth in a mouse xenograft model, were examined after long-term education with EVs. RNA sequencing was performed to investigate potential reprogramming induced by AT-EVs. Results: We found a positive correlation between protein amount per AT-EV and BMI. Quantitative proteomics of AT-EVs revealed 46 proteins that were significantly higher and 54 proteins that were significantly lower in specimens from women with a BMI ≥ 25 compared to women with a BMI < 25. AT-EVs from patients with a BMI ≥ 25 induced proliferation of MCF7 cells compared to AT-EVs from patients with a BMI < 25. Obese EVs induced a more aggressive phenotype in MDA-MB-231 cells, increasing their invasiveness in vitro. Obese EVs also increased the growth of MCF7 and MDA-MB-231 cells in vivo. Ingenuity pathway analysis of RNA-Seq data identified significant differences in mTOR signaling and canonical pathways associated with altered mitochondrial function. Conclusion: Our studies identify a novel mechanism to explain the obesity-breast cancer link in older women. Namely, that in obesity, the breast microenvironment produces EVs capable of reprogramming breast cancer cells to grow faster and be more aggressive. Identifying which cargo in breast AT-EV mediates these effects may provide new targets for intervention.

scholarly journals Breast adipose tissue macrophages (BATMs) have a stronger correlation with breast cancer survival than breast tumor stroma macrophages (BTSMs)

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Lili Lin ◽  
Christina Kuhn ◽  
Nina Ditsch ◽  
Thomas Kolben ◽  
Bastian Czogalla ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adipose Tissue ◽  
Breast Tumor ◽  
Poor Prognosis ◽  
Tumor Stroma ◽  
Cox Regression Analysis ◽  
Negatively Associated ◽  
Adipose Tissue Macrophages ◽  
Breast Adipose Tissue ◽  
Breast Adipose

Abstract Background An abundance of tumor-associated macrophages has been shown to be an independent prognostic factor for a poor prognosis of human breast cancer (BC). Adipose tissue accounts for the largest proportion of the breast and has also been identified as an independent indicator of poor survival in BC. This study aims to elucidate if the influence of adipose tissue in BC might be mediated by macrophages. The roles of macrophages in the breast tumor-stroma (breast tumor stroma macrophages, BTSM) and macrophages in the surrounding adipose tissue (breast adipose tissue macrophages, BATM) were explored separately. Methods Two hundred ninety-eight BC tissue samples were analyzed immunohistochemically. The number of macrophages was detected by CD68+ staining. The quantity of BATMs and BTSMs was correlated to clinical and pathological parameters as well as to disease-free survival (DFS) and overall survival (OS). Results The amounts of BATMs and BTSMs strongly correlated with each other (r = 0.5, p = 2.98E−15). The quantity of BTSMs, but not of BATMs, was significantly associated with the BC molecular subtype (p = 0.000011), and all triple-negative BC tumors contained high amounts of BTSMs. BATMs were negatively associated with DFS (p = 0.0332). Both BATMs (p = 0.000401) and BTSMs (p = 0.021) were negatively associated with OS in the Kaplan-Meier analysis, but only BATMs remained an independent factor in the multivariate Cox-regression analysis (HR = 4.464, p = 0.004). Combining prostaglandin E2 receptor 3 (EP3)-expression and the quantity of BATMs, a subgroup with an extremely poor prognosis could be identified (median OS 2.31 years in the “high BATMs/low EP3” subgroup compared to 11.42 years in the most favorable “low BATMs/high EP3” subgroup, p = 0.000002). Conclusion Our findings suggest that BTSMs and BATMs seem to be involved differently in BC. Breast adipose tissue might contribute to the aggressiveness of BC via BATMs, which were independently associated with BC survival. BATMs’ role and occurrence might be functionally dependent on EP3, as a combination of both factors was strongly associated with survival. Targeting BATMs—eventually in combination with targeting the EP3-pathway—might be promising for future therapies.

scholarly journals Breast Adipose Tissue Macrophages (BATMs) have a Stronger Correlation with Breast Cancer Survival than Breast Tumor Stroma Macrophages (BTSMs)

2020 ◽  
Author(s):  
Lili Lin ◽  
Christina Kuhn ◽  
Nina Ditsch ◽  
Thomas Kolben ◽  
Bastian Czogalla ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adipose Tissue ◽  
Breast Tumor ◽  
Poor Prognosis ◽  
Tumor Stroma ◽  
Cox Regression Analysis ◽  
Negatively Associated ◽  
Adipose Tissue Macrophages ◽  
Breast Adipose Tissue ◽  
Breast Adipose

Abstract Background: An abundance of tumor-associated macrophages has been shown to be an independent prognostic factor for a poor prognosis of human breast cancer (BC). Adipose tissue accounts for the largest proportion of the breast and has also been identified as an independent indicator of poor survival in BC. This study aims to elucidate, if the influence of adipose tissue in BC might be mediated by macrophages. The roles of macrophages in the breast tumor-stroma (breast tumor stroma macrophages, BTSM) and macrophages in the surrounding adipose tissue (breast adipose tissue macrophages, BATM) were explored separately.Methods: 298 BC tissue samples were analyzed immunohistochemically. The number of macrophages was detected by CD68+ staining. The quantity of BATMs and BTSMs was correlated to clinical and pathological parameters as well as to disease free survival (DFS) and overall survival (OS). Results: The amounts of BATMs and BTSMs strongly correlated with each other (r = 0.5, p < 0.001). The quantity of BTSMs, but not of BATMs, was significantly associated with the BC molecular subtype (p < 0.001) and all triple negative BC tumors contained high amounts of BTSMs. BATMs were negatively associated with DFS (p = 0.0332). Both BATMs (p < 0.001) and BTSMs (p = 0.021) were negatively associated with OS in the Kaplan-Meier analysis, but only BATMs remained an independent factor in the multivariate Cox-regression analysis (HR = 4.464, p = 0.004). Combining prostaglandin E2 receptor 3 (EP3)-expression and the quantity of BATMs, a subgroup with an extremely poor prognosis could be identified (median OS 2.31 years in the “high BATMs/low EP3” subgroup compared to 11.42 years in the most favorable “low BATMs/high EP3” subgroup, p < 0.001).Conclusion: Our findings suggest that BTSMs and BATMs seem to be involved differently in BC. Breast adipose tissue might contribute to the aggressiveness of BC via BATMs, which were independently associated with BC survival. BATMs’ role and occurrence might be functionally dependent on EP3, as a combination of both factors was strongly associated with survival. Targeting BATMs – eventually in combination with targeting the EP3-pathway – might be promising for future therapies.

Body Mass Index Influences Palpability but not Stage of Breast Cancer at Diagnosis

2007 ◽  
Vol 73 (6) ◽  
pp. 555-560 ◽  
Author(s):  
Anees B. Chagpar ◽  
Kelly M. Mcmasters ◽  
Jeremy Saul ◽  
Jacob Nurko ◽  
Robert C.G. Martin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Body Mass Index ◽  
Estrogen Receptor ◽  
Body Mass ◽  
North American ◽  
Tumor Size ◽  
Estrogen Receptor Status ◽  
Stage At Diagnosis ◽  
Histologic Subtype ◽  
The North

Body mass index (BMI) is associated with breast cancer risk, but its relationship with stage at diagnosis is unclear. BMI was calculated for patients in the North American Fareston and Tamoxifen Adjuvant trial, and was correlated with clinicopathologic factors, including stage at diagnosis. One thousand eight hundred fourteen patients were enrolled in the North American Fareston and Tamoxifen Adjuvant study; height and weight were recorded in 1451 (80%) of them. The median BMI was 27.1 kg/m2 (range, 14.7–60.7). The median patient age was 68 years (range, 42–100); median tumor size was 1.3 cm (range, 0.1–14 cm). One thousand seven hundred ninety-three (99.0%) patients were estrogen receptor positive, and 1519 (84.7%) were progesterone receptor positive. There was no significant relationship between BMI (as a continuous variable) and nodal status ( P = 0.469), tumor size ( P = 0.497), American Joint Committee on Cancer stage ( P = 0.167), grade ( P = 0.675), histologic subtype ( P = 0.179), or estrogen receptor status ( P = 0.962). Patients with palpable tumors, however, had a lower BMI than those with nonpalpable tumors (median 26.4 kg/m2 vs 27.5 kg/m2, P < 0.001). Similar results were found when BMI was classified as a categorical variable (<25 vs 25–29.9 vs ≥30). Increased BMI does not lead to a worse stage at presentation. Obese patients, however, tend to have nonpalpable tumors. Mammography in this population is especially important.

scholarly journals Obesity and Breast Cancer: The Role of Crown-Like Structures in Breast Adipose Tissue in Tumor Progression, Prognosis, and Therapy

2020 ◽  
Vol 23 (3) ◽  
pp. 233 ◽  
Author(s):  
Sara Socorro Faria ◽  
Luís Henrique Corrêa ◽  
Gabriella Simões Heyn ◽  
Lívia Pimentel de Sant'Ana ◽  
Raquel das Neves Almeida ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adipose Tissue ◽  
Tumor Progression ◽  
Breast Adipose Tissue ◽  
Breast Adipose

scholarly journals Low Levels of Omega-3 Long-Chain Polyunsaturated Fatty Acids Are Associated with Bone Metastasis Formation in Premenopausal Women with Breast Cancer: A Retrospective Study

Nutrients ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3832
Author(s):  
Caroline Goupille ◽  
Philippe G. Frank ◽  
Flavie Arbion ◽  
Marie-Lise Jourdan ◽  
Cyrille Guimaraes ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adipose Tissue ◽  
Bone Metastases ◽  
Premenopausal Women ◽  
Lymph Node Involvement ◽  
Axillary Lymph ◽  
Breast Adipose Tissue ◽  
Breast Adipose ◽  
Node Involvement ◽  
Low Levels

In the present study, we investigated various biochemical, clinical, and histological factors associated with bone metastases in a large cohort of pre- and postmenopausal women with breast cancer. Two hundred and sixty-one consecutive women with breast cancer were included in this study. Breast adipose tissue specimens were collected during surgery. After having established the fatty acid profile of breast adipose tissue by gas chromatography, we determined whether there were differences associated with the occurrence of bone metastases in these patients. Regarding the clinical and histological criteria, a majority of the patients with bone metastases (around 70%) had tumors with a luminal phenotype and 59% of them showed axillary lymph node involvement. Moreover, we found a negative association between the levels of n-3 long-chain polyunsaturated fatty acids (LC-PUFA) in breast adipose tissue and the development of bone metastases in premenopausal women. No significant association was observed in postmenopausal women. In addition to a luminal phenotype and axillary lymph node involvement, low levels of n-3 LC-PUFA in breast adipose tissue may constitute a risk factor that contributes to breast cancer bone metastases formation in premenopausal women.

scholarly journals Persistent Organic Pollutants and Breast Cancer: A Systematic Review and Critical Appraisal of the Literature

Cancers ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1063 ◽  
Author(s):  
Kaoutar Ennour-Idrissi ◽  
Pierre Ayotte ◽  
Caroline Diorio
Keyword(s):  
Breast Cancer ◽  
Systematic Review ◽  
Adipose Tissue ◽  
Organic Pollutants ◽  
Persistent Organic Pollutants ◽  
Cancer Incidence ◽  
Breast Cancer Incidence ◽  
Epidemiological Studies ◽  
Breast Adipose Tissue ◽  
Breast Adipose

Persistent organic pollutants (POPs) bioaccumulate in the food chain and have been detected in human blood and adipose tissue. Experimental studies demonstrated that POPs can cause and promote growth of breast cancer. However, inconsistent results from epidemiological studies do not support a causal relationship between POPs and breast cancer in women. To identify individual POPs that are repeatedly found to be associated with both breast cancer incidence and progression, and to demystify the observed inconsistencies between epidemiological studies, we conducted a systematic review of 95 studies retrieved from three main electronic databases. While no clear pattern of associations between blood POPs and breast cancer incidence could be drawn, POPs measured in breast adipose tissue were more clearly associated with higher breast cancer incidence. POPs were more consistently associated with worse breast cancer prognosis whether measured in blood or breast adipose tissue. In contrast, POPs measured in adipose tissue other than breast were inversely associated with both breast cancer incidence and prognosis. Differences in biological tissues used for POPs measurement and methodological biases explain the discrepancies between studies results. Some individual compounds associated with both breast cancer incidence and progression, deserve further investigation.

scholarly journals Novel semi-automated algorithm for high-throughput quantification of adipocyte size in breast adipose tissue, with applications for breast cancer microenvironment

Adipocyte ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 313-325
Author(s):  
Frank L. Lombardi ◽  
Naser Jafari ◽  
Kimberly A. Bertrand ◽  
Lauren J. Oshry ◽  
Michael R. Cassidy ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adipose Tissue ◽  
High Throughput ◽  
Cancer Microenvironment ◽  
Adipocyte Size ◽  
Automated Algorithm ◽  
Breast Adipose Tissue ◽  
Breast Adipose
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