Project description:Mitochondrial and oxidative stress have been related to obesity and breast cancer, and this cancer is more frequent and more aggressive in postmenopausal women with obesity. To investigate if Mexican-Mestizo postmenopausal women with breast cancer and obesity presented different somatic mutations in the mitochondrial DNA (mtDNA) when compared to women with normal body mass index.
Project description:Obesity is a risk factor for postmenopausal ERα (+) breast cancer. The metabolites from serum that contribute to this risk and how these factors affect ERα signaling are not known. Using whole metabolite profiling and a detection panel for proteins, we identified biomarkers that were differentially present in serum from obese vs. non-obese postmenopausal women, and we validated these factors in two separate cohorts of postmenopausal women who either developed breast cancer or those who were obese and lost weight after the onset of menopause. In vitro assays identified free fatty acids (FFAs), in particular oleic acid (OA) as serum factors that correlate with increased proliferation and aggressiveness in ERα(+) breast cancer cells by. FFAs activated both ERα and mTOR pathways and rewired metabolism in breast cancer cells. Pathway preferential estrogen-1 (PaPE-1), which target ERα and mTOR signaling, was able to block changes induced by FFAs. In fact, PaPEs were more effective in the presence of FFAs, suggesting a role for obesity-associated gene and metabolic rewiring in providing new targetable vulnerabilities for ERα-(+) breast cancer in postmenopausal women. Our findings provide a basis for preventing or inhibiting obesity-associated breast cancer by using PaPEs that would reverse these newly appreciated metabolic vulnerabilities of breast tumors in obese postmenopausal women.
Project description:The objective of the study was to comprehensively compare the genomic profiles in the breast of parous and nulliparous postmenopausal women to identify genes that permanently change their expression following pregnancy. The study was designed as a two-phase approach. In the discovery phase, we compared breast genomic profiles of 37 parous with 18 nulliparous postmenopausal women. In the validation phase, confirmation of the genomic patterns observed in the discovery phase was sought in an independent set of 30 parous and 22 nulliparous postmenopausal women.
Project description:It is widely accepted that a womanâs lifetime risk of developing breast cancer at menopause is reduced by early full term pregnancy and multiparity. This phenomenon is associated with the development and differentiation of the breast, which ultimately imprints a specific genomic profile in the mammary epithelium. In the present work we demonstrate that this profile represents a permanent signature that could be associated with the breast cancer risk reduction conferred by pregnancy. We have compared the gene expression profile of normal breast biopsies performed in 71 parous (P) and 42 nulliparous (NP) postmenopausal women. All samples were hybridized to Affymetrix HG_U133 Plus 2.0 oligonucleotide arrays. We compared the gene expression profile of normal breast core biopsies from 71 parous (women that had a full term pregnancy) and 42 nulliparous (women that never completed a pregnancy) postmenopausal women from Sweden. All samples were hybridized to Affymetrix HG_U133 Plus 2.0 oligonucleotide arrays.
Project description:Interventions: An observational study at the Dutch Screening for Breast Cancer will be performed in 66 postmenopausal women without breast cancer. By acquiring insight into the intestinal microbiota composition of postmenopausal women without breast cancer, a control group will be set up for already existing research lines in microbiota research in breast cancer patients at MUMC+. Fecal samples and questionnaires will be collected. The intestinal microbiota composition and absolute abundance of the fecal samples will be analyzed by with 16S rRNA Next Generation Sequencing (NGS) with subsequent qPCR to convert relative abundance to absolute abundance.
Primary outcome(s): The primary endpoints include the microbiota composition.
Study Design: N/A , unknown, Other
Project description:Analysis of breast cancer tumors following fulvestrant treatment for 4 weeks. Fulvestrant is a highly specific ER antagonist used to treat postmenopausal women with breast cancer. Data provide insight into the molecular mechanism of action of fulvestrant on whole genome expression.
Project description:RNA-sequencing was performed on patient mammary epithelial cell subsets from premenopausal and postmenopausal women undergoing breast reduction surgeries to interrogate transcriptional changes in postmenopausal cells.