Androgen and oestrogen receptor co-expression determines the efficacy of hormone receptor-mediated radiosensitisation in breast cancer.
Br J Cancer
; 127(5): 927-936, 2022 09.
Article
in En
| MEDLINE
| ID: mdl-35618789
ABSTRACT
PURPOSE:
Radiation therapy (RT) and hormone receptor (HR) inhibition are used for the treatment of HR-positive breast cancers; however, little is known about the interaction of the androgen receptor (AR) and estrogen receptor (ER) in response to RT in AR-positive, ER-positive (AR+/ER+) breast cancers. Here we assessed radiosensitisation of AR+/ER+ cell lines using pharmacologic or genetic inhibition/degradation of AR and/or ER.METHODS:
Radiosensitisation was assessed with AR antagonists (enzalutamide, apalutamide, darolutamide, seviteronel, ARD-61), ER antagonists (tamoxifen, fulvestrant) or using knockout of AR.RESULTS:
Treatment with AR antagonists or ER antagonists in combination with RT did not result in radiosensitisation changes (radiation enhancement ratios [rER] 0.76-1.21). Fulvestrant treatment provided significant radiosensitisation of CAMA-1 and BT-474 cells (rER 1.06-2.0) but not ZR-75-1 cells (rER 0.9-1.11). Combining tamoxifen with enzalutamide did not alter radiosensitivity using a 1 h or 1-week pretreatment (rER 0.95-1.14). Radiosensitivity was unchanged in AR knockout compared to Cas9 cells (rER 1.07 ± 0.11), and no additional radiosensitisation was achieved with tamoxifen or fulvestrant compared to Cas9 cells (rER 0.84-1.19).CONCLUSION:
While radiosensitising in AR + TNBC, AR inhibition does not modulate radiation sensitivity in AR+/ER+ breast cancer. The efficacy of ER antagonists in combination with RT may also be dependent on AR expression.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Radiation Tolerance
/
Breast Neoplasms
/
Receptors, Androgen
/
Receptors, Estrogen
Limits:
Female
/
Humans
Language:
En
Journal:
Br J Cancer
Year:
2022
Type:
Article
Affiliation country:
United States