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Effects of Estradiol/Micronized Progesterone vs. Conjugated Equine Estrogens/Medroxyprogesterone Acetate on Breast Cancer Gene Expression in Healthy Postmenopausal Women
- Source :
- International Journal of Molecular Sciences, Volume 24, Issue 4, Pages: 4123
- Publication Year :
- 2023
- Publisher :
- MDPI AG, 2023.
-
Abstract
- Recent studies suggest estradiol (E2)/natural progesterone (P) confers less breast cancer risk compared with conjugated equine estrogens (CEE)/synthetic progestogens. We investigate if differences in the regulation of breast cancer-related gene expression could provide some explanation. This study is a subset of a monocentric, 2-way, open observer-blinded, phase 4 randomized controlled trial on healthy postmenopausal women with climacteric symptoms (ClinicalTrials.gov; EUCTR-2005/001016-51). Study medication was two 28-day cycles of sequential hormone treatment with oral 0.625 mg CEE and 5 mg of oral medroxyprogesterone acetate (MPA) or 1.5 mg E2 as percutaneous gel/day with the addition of 200 mg oral micronized P. MPA and P were added days 15–28/cycle. Material from two core-needle breast biopsies in 15 women in each group was subject to quantitative PCR (Q-PCR). The primary endpoint was a change in breast carcinoma development gene expression. In the first eight consecutive women, RNA was extracted at baseline and after two months of treatment and subjected to microarray for 28856 genes and Ingenuity Pathways Analysis (IPA) to identify risk factor genes. Microarray analysis showed 3272 genes regulated with a fold-change of >±1.4. IPA showed 225 genes belonging to mammary-tumor development function: 198 for CEE/MPA vs. 34 for E2/P. Sixteen genes involved in mammary tumor inclination were subject to Q-PCR, inclining the CEE/MPA group towards an increased risk for breast carcinoma compared to the E2/P group at a very high significance level (p = 3.1 × 10−8, z-score 1.94). The combination of E2/P affected breast cancer-related genes much less than CEE/MPA.
- Subjects :
- menopausal hormone treatment and breast cancer risk
Organic Chemistry
estradiol/micronized progesterone
General Medicine
breast cancer gene expression
healthy postmenopausal women
Catalysis
Computer Science Applications
Inorganic Chemistry
core needle biopsies
Physical and Theoretical Chemistry
conjugated equine estrogens/medroxyprogesterone acetate
Molecular Biology
Spectroscopy
Subjects
Details
- ISSN :
- 14220067
- Volume :
- 24
- Database :
- OpenAIRE
- Journal :
- International Journal of Molecular Sciences
- Accession number :
- edsair.doi.dedup.....2534264b9faea6eb14e6728710456b2e
- Full Text :
- https://doi.org/10.3390/ijms24044123