scholarly journals Mammary developmental fate and breast cancer risk

2005 ◽  
Vol 12 (3) ◽  
pp. 483-495 ◽  
Author(s):  
Daniel Medina
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Mammary Epithelial Cells ◽  
Research Area ◽  
Mammary Epithelial ◽  
Protective Effects ◽  
Intrinsic Factors ◽  
Developmental Fate ◽  
Long Time

The ovarian hormones, estrogen and progesterone, play a pivotal role in normal and neoplastic development of the mammary gland. These hormones have a paradoxical role as long duration of estrogen and progesterone are associated with increased breast cancer risk, while short duration of pregnancy level doses are associated with a reduced breast cancer risk. The protective effects of estrogen and progesterone, as well as pregnancy, have been extensively studied in animal models. Recent studies have demonstrated that these hormones induce alterations in gene expression in the mammary epithelial cells which persist for a long time after the hormones are withdrawn from the host. It is postulated that hormones induce a switch in mammary developmental fate which decreases the risk of breast cancer over the lifetime of the host. Some of the possible cellular pathways persistently altered by short term hormone exposure are a decrease in growth factors and an increase in apoptosis. The expression of these genes, in turn, may be affected by alterations in genes regulating chromatin remodeling. The relative contributions of host-mediated factors and mammary cell intrinsic factors remain to be determined. The current studies have moved this research area from the biological to the molecular realm and offer the potential for directing prevention efforts at specific molecular targets.

scholarly journals The Proliferative Activity of Mammary Epithelial Cells in Normal Tissue Predicts Breast Cancer Risk in Premenopausal Women

2016 ◽  
Vol 76 (7) ◽  
pp. 1926-1934 ◽  
Author(s):  
Sung Jin Huh ◽  
Hannah Oh ◽  
Michael A. Peterson ◽  
Vanessa Almendro ◽  
Rong Hu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Epithelial Cells ◽  
Cancer Risk ◽  
Proliferative Activity ◽  
Normal Tissue ◽  
Mammary Epithelial Cells ◽  
Premenopausal Women ◽  
Mammary Epithelial

scholarly journals A Breast Tissue Protein Expression Profile Contributing to Early Parity-Induced Protection Against Breast Cancer

2015 ◽  
Vol 37 (5) ◽  
pp. 1671-1685 ◽  
Author(s):  
Christina Marie Gutierrez ◽  
Rebecca Lopez-Valdez ◽  
Ramadevi Subramani ◽  
Arunkumar Arumugam ◽  
Sushmita Nandy ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Protein Expression ◽  
Breast Tissue ◽  
Expression Profiles ◽  
Genomic Stability ◽  
Protective Effects ◽  
Nulliparous Women ◽  
Protein Expression Profiles

Background/Aims: Early parity reduces breast cancer risk, whereas, late parity and nulliparity increase breast cancer risk. Despite substantial efforts to understand the protective effects of early parity, the precise molecular circuitry responsible for these changes is not yet fully defined. Methods: Here, we have conducted the first study assessing protein expression profiles in normal breast tissue of healthy early parous, late parous, and nulliparous women. Breast tissue biopsies were obtained from 132 healthy parous and nulliparous volunteers. These samples were subjected to global protein expression profiling and immunohistochemistry. GeneSpring and MetaCore bioinformatics analysis software were used to identify protein expression profiles associated with early parity (low risk) versus late/nulliparity (high risk). Results: Early parity reduces expression of key proteins involved in mitogenic signaling pathways in breast tissue through down regulation of EGFR1/3, ESR1, AKT1, ATF, Fos, and SRC. Early parity is also characterized by greater genomic stability and reduced tissue inflammation based on differential expression of aurora kinases, p53, RAD52, BRCA1, MAPKAPK-2, ATF-1, ICAM1, and NF-kappaB compared to late and nulli parity. Conclusions: Early parity reduces basal cell proliferation in breast tissue, which translates to enhanced genomic stability, reduced cellular stress/inflammation, and thus reduced breast cancer risk.

scholarly journals Differential protective effects of bisphosphonates and denosumab on primary breast cancer risk, potentially to be modified by statins: a retrospective study using electronic health records

2020 ◽  
Author(s):  
Alexander Stanoyevitch ◽  
Lei Zhang ◽  
Javier Sanz ◽  
Robert Follett ◽  
Douglas Bell
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Elderly Women ◽  
Previous History ◽  
Bivariate Analysis ◽  
Control Group ◽  
Protective Effects ◽  
Significant Difference

Abstract Background: The risks of osteoporosis and breast cancer are increasing in elderly women, as well as hyperlipidemia. Bisphosphonates and denosumab are recommended for treatment of osteoporosis, and statins are used for hyperlipidemia. There are different and overlapping pharmacodynamics among bisphosphonates, denosumab and statins. We aim to assess effects of bisphosphonates and denosumab on breast cancer, possibly affected by statins use.Methods: This retrospective cohort is consisted of 97,671 women elder than 50 years with no previous history of malignancy and no cancer other than breast during follow-up, including 778, 2326, 15287 and 7631denosumab, bisphosphonates, statins and hormone for postmenopausal symptoms ever users. Univariate and bivariate analysis, and the Cox Proportional Hazards multi-variate model are performed.Results: Over an average of 3.6 years follow up, the breast cancer risks counted after 365 days of latency are 1.54% (12/778) for denosumab, 0.52% (12/2326) for bisphosphonates, compared to 0.65% (99/15287) in statins ever use group, 0.26% (20/7631) in hormone users for menopausal symptoms and 1.38% (1032/74867) in control group. The significant difference of breast cancer risk between denosumab and bisphosphonates group (p=0.0047) is supported by the Log-rank test (p=0.0004). The multivariate model is in partial agreement with the uni- and bivariate analysis. Further subgroup analysis revealed that concurrent use of statins in denosumab prescribers lowered the breast cancer risk to 0.89% (2/224), but with no significantly change of breast cancer risk in bisphosphonates group (7/919, 0.762%).Conclusion : Our data suggest superior protective effects of bisphosphonates over denosumab on breast cancer risk in elderly women. Statins could potentially exert breast cancer protective effect in denosumab users with no synergistic effect in patients taking bisphosphonates. A large scale study with long term follow up is needed.

scholarly journals Lifelong n-3 Polyunsaturated Fatty Acid Exposure Modulates Size of Mammary Epithelial Cell Populations and Expression of Caveolae Resident Proteins in Fat-1 Mice

Nutrients ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 2477
Author(s):  
Hillyer ◽  
Kang ◽  
Ma
Keyword(s):  
Breast Cancer ◽  
Mammary Gland ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Surface Expression ◽  
Mammary Epithelial ◽  
Similar Amount ◽  
Omega 3 ◽  
Reduce Breast Cancer Risk ◽  
Her 2

Omega-3 polyunsaturated fatty acids (n-3 PUFA) have been associated with reduced breast cancer risk; however, the exact mechanism remains elusive. Female wildtype (WT) and fat-1 mice were fed a 10% safflower diet until 6 weeks of age. Mammary gland epithelial cells (EC) were isolated and EC populations were determined by CD24 surface expression. Fat-1 mice expressed 65%, 20%, and 15% while WT mice expressed 65%, 26% and 9% for non-, myo- and luminal ECs, respectively. The luminal EC population was significantly greater in fat-1 mice (p ≤ 0.05), while the total number of mammary ECs were similar between groups (p = 0.79). Caveolae was isolated from ECs and Her-2/neu, ER-α and cav-1 protein expression was determined by Western blotting. Fat-1 mice had a two-fold greater ER-α (p ≤ 0.05) and a 1.5-fold greater cav-1 (p ≤ 0.05) expression than WT with a similar amount of Her-2/neu protein (p = 0.990) between groups. Overall, this study provides novel mechanistic evidence by which n-3 PUFA modifies early mammary gland development that may potentially reduce breast cancer risk later in life.

scholarly journals Identifying breast cancer risk loci by global differential allele-specific expression (DASE) analysis in mammary epithelial transcriptome

BMC Genomics ◽  
2012 ◽  
Vol 13 (1) ◽  
pp. 570 ◽  
Author(s):  
Chuan Gao ◽  
Karthik Devarajan ◽  
Yan Zhou ◽  
Carolyn M Slater ◽  
Mary B Daly ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Mammary Epithelial ◽  
Specific Expression ◽  
Allele Specific Expression ◽  
Allele Specific

scholarly journals Transforming Growth Factor-β and Breast Cancer Risk in Women With Mammary Epithelial Hyperplasia

1999 ◽  
Vol 91 (24) ◽  
pp. 2096-2101 ◽  
Author(s):  
Helenice Gobbi ◽  
William D. Dupont ◽  
Jean F. Simpson ◽  
W.Dale Plummer ◽  
Peggy A. Schuyler ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Growth Factor ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Mammary Epithelial ◽  
Epithelial Hyperplasia

scholarly journals Paracrine-Acting Adiponectin Promotes Mammary Epithelial Differentiation and Synergizes with Genistein to Enhance Transcriptional Response to Estrogen Receptor β Signaling

Endocrinology ◽  
2011 ◽  
Vol 152 (9) ◽  
pp. 3409-3421 ◽  
Author(s):  
Omar M. Rahal ◽  
Rosalia C. M. Simmen
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Estrogen Receptor ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Soy Protein Isolate ◽  
Dietary Exposure ◽  
Dietary Factors ◽  
Mammary Epithelial ◽  
Mammary Tissue

Mammary stromal adipocytes constitute an active site for the synthesis of the adipokine, adiponectin (APN) that may influence the mammary epithelial microenvironment. The relationship between “local,” mammary tissue-derived APN and breast cancer risk is poorly understood. Here, we identify a novel mechanism of APN-mediated signaling that influences mammary epithelial cell proliferation, differentiation, and apoptosis to modify breast cancer risk. We demonstrate that early dietary exposure to soy protein isolate induced mammary tissue APN production without corresponding effects on systemic APN levels. In estrogen receptor (ER)-negative MCF-10A cells, recombinant APN promoted lobuloalveolar differentiation by inhibiting oncogenic signal transducer and activator of transcription 3 activity. In ER-positive HC11 cells, recombinant APN increased ERβ expression, inhibited cell proliferation, and induced apoptosis. Using the estrogen-responsive 4X-estrogen response element promoter-reporter construct to assess ER transactivation and small interfering RNA targeting of ERα and ERβ, we show that APN synergized with the soy phytoestrogen genistein to promote ERβ signaling in the presence of estrogen (17β-estradiol) and ERβ-specific agonist 2,3-bis(4-hydroxyphenyl)-propionitrile and to oppose ERα signaling in the presence of the ERα-specific agonist 4,4′,4′-(4-propyl-(1H)-pyrazole-1,3,5-triyl)trisphenol. The enhancement of ERβ signaling with APN + genistein cotreatments was associated with induction of apoptosis, increased expression of proapoptotic/prodifferentiation genes (Bad, p53, and Pten), and decreased antiapoptotic (Bcl2 and survivin) transcript levels. Our results suggest that mammary-derived APN can influence adjacent epithelial function by ER-dependent and ER-independent mechanisms that are consistent with reduction of breast cancer risk and suggest local APN induction by dietary factors as a targeted approach for promotion of breast health.

Plasma Phytoestrogens and Subsequent Breast Cancer Risk

2007 ◽  
Vol 25 (6) ◽  
pp. 648-655 ◽  
Author(s):  
Martijn Verheus ◽  
Carla H. van Gils ◽  
Lital Keinan-Boker ◽  
Philip B. Grace ◽  
Sheila A. Bingham ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Postmenopausal Women ◽  
Plasma Levels ◽  
Conditional Logistic Regression ◽  
Protective Effects ◽  
Perimenopausal Women ◽  
Liquid Chromatography Tandem Mass ◽  
Nested Case Control

Purpose Phytoestrogens are plant compounds that are structurally and functionally similar to mammalian estrogens. By competing for estrogen receptors, phytoestrogens possibly inhibit binding of the more potent endogenous estrogens and decrease their potential effects on breast cancer risk. We investigated the association between plasma phytoestrogen levels and breast cancer risk in a prospective manner. Patients and Methods We performed a nested case-control study within the Prospect cohort, one of the two Dutch cohorts participating in the European Prospective Investigation into Cancer and Nutrition. A total of 383 women (87 pre- or perimenopausal women [mean age, 52 years] and 296 postmenopausal women [mean age, 59 years]) who developed breast cancer were selected as case subjects and were matched to 383 controls, on date of blood sampling. Plasma levels of isoflavones (daidzein, genistein, glycitein, O-desmethylangolensin, and equol) and lignans (enterodiol and enterolactone) were measured. The isotope dilution liquid chromatography/tandem mass-spectrometry method incorporating triply 13C-labeled standards was used for all analyses. Breast cancer odds ratios were calculated for tertiles of phytoestrogen plasma levels using conditional logistic regression analysis. Results For genistein, the risk estimate for the highest versus the lowest tertile was 0.68 (95% CI, 0.47 to 0.98). Similar protective effects, although not statistically significant, were seen for the other isoflavones. Lignan levels did not appear to be related to breast cancer risk. Results were the same in pre- or perimenopausal women, and in postmenopausal women. Conclusion High genistein circulation levels are associated with reduced breast cancer risk in the Dutch population. No effects of lignans on breast cancer risk were observed.

Testosterone and risk of breast cancer: appraisal of existing evidence

2010 ◽  
Vol 2 (1) ◽  
Author(s):  
Abdulmaged M. Traish ◽  
Katharina Fetten ◽  
Martin Miner ◽  
Michael L. Hansen ◽  
Andre Guay
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Tumor Cell ◽  
Polycystic Ovary ◽  
Epidemiological Studies ◽  
Sexual Disorders ◽  
Androgen Treatment ◽  
Increased Risk ◽  
Long Time

AbstractThe objective of this review was to examine data from preclinical, clinical and epidemiological studies to evaluate if testosterone (T) poses increased risk of breast cancer in women. Appraisal of the existing literature produced several lines of evidence arguing against increased breast cancer risk with T. These include: (i) Data from breast tumor cell lines treated with androgens did not corroborate the notion that T increases breast cancer risk. On the contrary, androgens appear to be protective, as they inhibit tumor cell growth. (ii) Many of the epidemiological studies claiming an association between T and breast cancer did not adjust for estrogen levels. Studies adjusted for estrogen levels reported no association between T and breast cancer. (iii) Data from clinical studies with exogenous androgen treatment of women with endocrine and sexual disorders did not show any increase in incidence of breast cancer. (iv) Women afflicted with polycystic ovary disease, who exhibit high levels of androgens do not show increased risk of breast cancer compared to the general population. (v) Female to male transsexuals, who receive supraphysiological doses of T for long time periods prior to surgical procedures, do not report increased risk of breast cancer. (vi) Finally, women with hormone responsive primary breast cancer are treated with aromatase inhibitors, which block conversion of androgens to estrogens, thus elevating androgen levels. These women do not experience increased incidence of contralateral breast cancer nor do they experience increased tumor growth. In conclusion, the evidence available strongly suggests that T does not increase breast cancer risk in women.

Sign in / Sign up

Export Citation Format

Share Document