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

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.

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

Cancers ◽

10.3390/cancers11081063 ◽

2019 ◽

Vol 11 (8) ◽

pp. 1063 ◽

Cited By ~ 3

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.

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

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.1831 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Cited By ~ 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.

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Breast cancer and expression of aromatase in breast adipose tissue

Trends in Endocrinology and Metabolism ◽

10.1016/1043-2760(94)90092-2 ◽

1994 ◽

Vol 5 (3) ◽

pp. 113-120 ◽

Cited By ~ 23

Author(s):

Serdar E. Bulun ◽

Evan R. Simpson

Keyword(s):

Breast Cancer ◽

Adipose Tissue ◽

Breast Adipose Tissue ◽

Breast Adipose

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Vitamin E concentration in breast adipose tissue of breast cancer patients (Kuopio, Finland)

Cancer Causes & Control ◽

10.1007/bf00051701 ◽

1996 ◽

Vol 7 (6) ◽

pp. 591-595 ◽

Cited By ~ 8

Author(s):

Zhenrong Zhu ◽

Markku Parviainen ◽

Satu M�nnist� ◽

Pirjo Pietinen ◽

Matti Eskelinen ◽

...

Keyword(s):

Breast Cancer ◽

Adipose Tissue ◽

Vitamin E ◽

Cancer Patients ◽

Breast Cancer Patients ◽

Breast Adipose Tissue ◽

Breast Adipose

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17β Hydroxysteroid dehydrogenase activity in breast adipose tissue from breast cancer patients

Journal of Steroid Biochemistry ◽

10.1016/0022-4731(87)91513-5 ◽

1987 ◽

Vol 28 ◽

pp. 143 ◽

Cited By ~ 2

Author(s):

J.S. O'Neill ◽

W.R. Miller

Keyword(s):

Breast Cancer ◽

Adipose Tissue ◽

Cancer Patients ◽

Dehydrogenase Activity ◽

Hydroxysteroid Dehydrogenase ◽

Breast Cancer Patients ◽

Breast Adipose Tissue ◽

Breast Adipose

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Detection of crown-like structures in breast adipose tissue and clinical outcomes among African-American and White women with breast cancer

Breast Cancer Research ◽

10.1186/s13058-020-01308-4 ◽

2020 ◽

Vol 22 (1) ◽

Author(s):

Maret L. Maliniak ◽

Aswathy Miriam Cheriyan ◽

Mark E. Sherman ◽

Yuan Liu ◽

Keerthi Gogineni ◽

...

Keyword(s):

Breast Cancer ◽

Adipose Tissue ◽

African American ◽

Clinical Outcomes ◽

White Women ◽

Breast Adipose Tissue ◽

Breast Adipose

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Omega-3 fatty acids and ERPR(-) and HER2/neu(+/-) breast cancer prevention.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.tps1589 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. TPS1589-TPS1589

Author(s):

Chidimma Kalu ◽

Sarah Woelke ◽

Jianying Zhang ◽

Martha Belury ◽

Rulong Shen ◽

...

Keyword(s):

Breast Cancer ◽

Fatty Acids ◽

Adipose Tissue ◽

Fatty Acid ◽

Corn Oil ◽

Breast Cancer Subtypes ◽

Cancer Subtypes ◽

Her2 Breast Cancer ◽

Breast Adipose Tissue ◽

Breast Adipose

TPS1589 Background: The most aggressive breast cancer subtypes tend to be estrogen and progesterone receptor negative (ERPR(-)) and human epidermal growth factor receptor type 2 positive (HER2(+)). Women with these breast cancer subtypes (triple negative, ERPR(-)HER2(+)) tend to experience worse clinical outcomes and have a relatively higher risk of recurrence. Our previous research demonstrated that dietary omega-3 (n-3) fatty acids can significantly inhibit ERPR(-) HER2(+) tumorigenesis in MMTV-HER2/neu transgenic mice fed fish oil vs corn oil-based diets. The fish oil diet group developed 30% fewer breast tumors, had lower Ki67 expression, and experienced less mammary atypia relative to the corn oil diet group. Other studies involving diet, nutrition and breast cancer point to the potentially protective effect of an anti-inflammatory diet on the risk of developing ER(-) and HER2(+) breast cancer, further supporting the evidence that the ERPR(-), HER2(±) subtypes may be highly responsive to this bioactive nutrient. Methods: This is a double-blinded, randomized clinical trial of high dose (~5.4 g EPA+DHA) vs low dose (~0.9 g EPA+DHA in fatty acid mix of the typical American diet) of n-3 fatty acids in breast cancer survivors of ERPR(-), HER2(±) breast cancer. Eligible participants will take 5 capsules/day for 12 months, with cellular samples of breast epithelial and/or adipose tissue obtained by fine needle aspirations of the contralateral breast. The study aims to determine whether n-3 fatty acid supplementation will modify fatty acid metabolite content in breast adipose tissue, modulate cytomorphology and/or cell proliferation in breast epithelial cells, affect DNA methylation patterns, and modulate pro- vs anti-inflammatory gene expression patterns in breast adipose tissue. Correlative aims will evaluate possible associations between factors such as breast adipose tissue, red cell membrane fatty acid profiles, BMI, and reported dietary intake. Sample size of 40 participants per arm was calculated to provide at least 80% power to detect a statistically significant difference for each primary endpoint. This study focuses on women survivors of high risk breast cancer subtypes, specifically triple negative or ERPR(-)HER2(+) disease, who are currently without long term adjuvant options. Eligibility criteria include prior diagnosis of ERPR(-) stage 0 to III breast cancer, ≤5 years from completion of standard therapy.The study was closed to accrual in November 2018; less than 9 months of follow-up remain for active study participants. Clinical trial information: NCT02295059.

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