Dataset Information
Prolonged recombinant pregnancy hormone use in BRCA1 and BRCA2 mutation carriers.
Ontology highlight
ABSTRACT: Background
An early first full-time pregnancy substantially reduces the risk of developing breast cancer later in life. Extensive studies indicate that this protective effect is mediated by the pregnancy hormone human chorionic gonadotrophin (hCG).Methods
In this proof-of-concept study 33 women with a BRCA mutation received recombinant-hCG (r-hCG). A 4-mm breast biopsy was obtained before (T1) and after 12 weeks of r-hCG injections (T2), as well as 6 months later (T3). The tissue was examined using RNA-sequencing methodology to determine if the 'high-risk' transcriptomic signature was converted to a 'low-risk' signature as in an early first full-time pregnancy. A stringent clinical safety monitoring was performed.Results
The r-hCG administration was well tolerated in all participants. No clinically relevant changes were observed. In 25 women, the RNA quality was good for RNA sequencing in all three breast tissue biopsies. In response to the r-hCG, we observed 1907 differentially expressed genes (DEGs) (1032 up, 875 down) at T2 vs. T1 and 1065 DEGs (897 up, 168 down) at T3 vs. T1 in the group of women (n = 11) not using any hormonal contraceptives during the study. There was no response at T2 vs. T1 and a small number of DEGs, 260 (214 up, 46 down) at T3 vs. T1 in the group of 14 women using contraceptives.Conclusions
In summary, r-hCG has a remarkable effect on the gene expression profile of breast tissues from BRCA1/2 carriers who did not use any contraception. This opens an opportunity for a novel preventive strategy to reduce the incidence of breast cancer.
SUBMITTER: Depypere H
PROVIDER: S-EPMC8011504 | biostudies-literature | 2021 May
REPOSITORIES: biostudies-literature
Publications
Prolonged recombinant pregnancy hormone use in BRCA1 and BRCA2 mutation carriers.
European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP) 20210501 3
<h4>Background</h4>An early first full-time pregnancy substantially reduces the risk of developing breast cancer later in life. Extensive studies indicate that this protective effect is mediated by the pregnancy hormone human chorionic gonadotrophin (hCG).<h4>Methods</h4>In this proof-of-concept study 33 women with a BRCA mutation received recombinant-hCG (r-hCG). A 4-mm breast biopsy was obtained before (T1) and after 12 weeks of r-hCG injections (T2), as well as 6 months later (T3). The tissue ...[more]