Genotype-phenotype interactions in the estradiol pathway.
Endogenous estrogen is a known risk factor for breast and ovarian cancer and hormonal therapy is widely used in clinical practice. Estrogen is therefore a target for susceptibility and treatment response studies. Genetic variations in the enzymes that determine its levels: CYP17, CYP11a, CYP19, hydroxysteroid hydrogenase, steroid sulphatase, CYP1A1, CYP3A4, CYP1B are likely to modify the risk for breast cancer and treatment with antiestrogens and aromatase inhibitors.
Figure. The relationship between the oestrogens found in tissues and in circulation and transcriptional activation by the ER-ERE-Complex, mechanisms of acquired resistance to aromatase inhibitors and antiestrogens.
(click to enlarge)
Torland LA, Geisler J, Azimzade Y, Frafjord A, Røed Nilsen H, Buer L, Lømo J, Garred Ø, Tahiri A, Lyngra M, Øynebråten I, Corthay A, Sahlberg K, Kristensen V, Tekpli X(2026) Multi-platform analysis of the tumor immune microenvironment associated with breast cancer subtypes Oncoimmunology, 15(1), 2610535 DOI 10.1080/2162402X.2025.2610535, PubMed 41530924
Billaud A, Figlioli G, Mooser C, Casamassima I, Azzoni V, Srivatsa J, Colombo M, Caleca L, Ahearn TU, Andrulis IL, Antoniou AC, Beckmann MW, Behrens S, Bermisheva M, Bogdanova NV, Bolla MK, Bonanni B, Brüning T, Camp NJ, Campbell A, Castelao JE, Cessna MH, Chang-Claude J, NBCS Collaborators, Czene Ket al.(2025) Large-scale meta-analysis and precision functional assays identify FANCM regions in which PTVs confer different risks for ER-negative and triple-negative breast cancer Breast, 85, 104619(in press) DOI 10.1016/j.breast.2025.104619, PubMed 41223770
Lawrenson K, Kar S, McCue K, Kuchenbaeker K, Michailidou K, Tyrer J, Beesley J, Ramus SJ, Li Q, Delgado MK, Lee JM, Aittomäki K, Andrulis IL, Anton-Culver H, Arndt V, Arun BK, Arver B, Bandera EV, Barile M, Barkardottir RB, Barrowdale D, Beckmann MW, Benitez J, Berchuck A, Bisogna Met al.(2025) Author Correction: Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus Nat Commun, 16(1), 8237 DOI 10.1038/s41467-025-63507-x, PubMed 40925936
