Weighing the Risk: effects of Obesity on the Mammary Gland and Breast Cancer Risk

Hillers‐Ziemer, Lauren E.; Arendt, Lisa M.

doi:10.1007/s10911-020-09452-5

Cited by 12 publications

(6 citation statements)

References 220 publications

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“…Thus, the translational relevance of the study is limited. Indeed, it has been documented that the mechanical and biochemical properties of the adipose tissue can promote malignancy -at least in breast cancer [40][41][42]. Follow up studies using orthotopic models are critical to confirm findings and for translation to human patients.…”

Section: Discussionmentioning

confidence: 99%

High-fat diet-fed ovariectomized mice are susceptible to accelerated subcutaneous tumor growth potentially through adipose tissue inflammation, local insulin-like growth factor release, and tumor associated macrophages

et al. 2020

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Section: Discussionmentioning

confidence: 99%

High-fat diet-fed ovariectomized mice are susceptible to accelerated subcutaneous tumor growth potentially through adipose tissue inflammation, local insulin-like growth factor release, and tumor associated macrophages

et al. 2020

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“…Adipocytes: Adipocytes are potent sources of cytokines that can modulate breast tumorigenesis [170,225]. Interestingly, estrone, but not 17β-estradiol, was able to sharply increase mRNAs for CCL2, IL-6, and IL-8 in isolated primary adipocytes [170].…”

Section: Myofibroblasts/cancer-associated Fibroblasts (Cafs)/immune Cellsmentioning

confidence: 99%

Endogenous and Therapeutic Estrogens: Maestro Conductors of the Microenvironment of ER+ Breast Cancers

Schuler

Murdoch

2021

Cancers

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Estrogen receptor alpha (ERα) marks heterogeneous breast cancers which display a repertoire of somatic genomic mutations and an immune environment that differs from other breast cancer subtypes. These cancers also exhibit distinct biological behaviors; despite an overall better prognosis than HER2+ or triple negative breast cancers, disseminated dormant cells can lead to disease recurrence decades after the initial diagnosis and treatment. Estrogen is the best studied driver of these cancers, and antagonism or reduction of estrogen activity is the cornerstone of therapeutic approaches. In addition to reducing proliferation of ERα+ cancer cells, these treatments also alter signals to multiple other target cells in the environment, including immune cell subpopulations, cancer-associated fibroblasts, and endothelial cells via several distinct estrogen receptors. In this review, we update progress in our understanding of the stromal cells populating the microenvironments of primary and metastatic ER+ tumors, the effects of estrogen on tumor and stromal cells to modulate immune activity and the extracellular matrix, and net outcomes in experimental and clinical studies. We highlight new approaches that will illuminate the unique biology of these cancers, provide the foundation for developing new treatment and prevention strategies, and reduce mortality of this disease.

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“…Raloxifene is less likely to cause endometrial cancer, but its use results in increased risk of cataracts and blood clots [7]. Notably, with the rise in obesity in the US (and world-wide), and the associated increase in BC risk [10], it is imperative to develop simple and effective strategies to prevent BC.…”

Section: Introductionmentioning

confidence: 99%

Cumin Prevents 17β-Estradiol-Associated Breast Cancer in ACI Rats

Aqil

Jeyabalan

Munagala

et al. 2021

IJMS

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Breast cancer (BC) is a leading cause of cancer deaths in women in less developed countries and the second leading cause of cancer death in women in the U.S. In this study, we report the inhibition of E2-mediated mammary tumorigenesis by Cuminum cyminum (cumin) administered via the diet as cumin powder, as well as dried ethanolic extract. Groups of female ACI rats were given either an AIN-93M diet or a diet supplemented with cumin powder (5% and 7.5%, w/w) or dried ethanolic cumin extract (1%, w/w), and then challenged with subcutaneous E2 silastic implants (1.2 cm; 9 mg). The first appearance of a palpable mammary tumor was significantly delayed by both the cumin powder and extract. At the end of the study, the tumor incidence was 96% in the control group, whereas only 55% and 45% animals had palpable tumors in the cumin powder and extract groups, respectively. Significant reductions in tumor volume (660 ± 122 vs. 138 ± 49 and 75 ± 46 mm3) and tumor multiplicity (4.21 ± 0.43 vs. 1.16 ± 0.26 and 0.9 ± 0.29 tumors/animal) were also observed by the cumin powder and cumin extract groups, respectively. The cumin powder diet intervention dose- and time-dependently offset E2-related pituitary growth, and reduced the levels of circulating prolactin and the levels of PCNA in the mammary tissues. Mechanistically, the cumin powder diet resulted in a significant reversal of E2-associated modulation in ERα, CYP1A1 and CYP1B1. Further, the cumin powder diet reversed the expression levels of miRNAs (miR-182, miR-375, miR-127 and miR-206) that were highly modulated by E2 treatment. We analyzed the composition of the extract by GC/MS and established cymene and cuminaldehyde as major components, and further detected no signs of gross or systemic toxicity. Thus, cumin bioactives can significantly delay and prevent E2-mediated mammary tumorigenesis in a safe and effective manner, and warrant continued efforts to develop these clinically translatable spice bioactives as chemopreventives and therapeutics against BC.

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Weighing the Risk: effects of Obesity on the Mammary Gland and Breast Cancer Risk

Cited by 12 publications

References 220 publications

High-fat diet-fed ovariectomized mice are susceptible to accelerated subcutaneous tumor growth potentially through adipose tissue inflammation, local insulin-like growth factor release, and tumor associated macrophages

High-fat diet-fed ovariectomized mice are susceptible to accelerated subcutaneous tumor growth potentially through adipose tissue inflammation, local insulin-like growth factor release, and tumor associated macrophages

Endogenous and Therapeutic Estrogens: Maestro Conductors of the Microenvironment of ER+ Breast Cancers

Cumin Prevents 17β-Estradiol-Associated Breast Cancer in ACI Rats

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