Improved relapse-free survival on aromatase inhibitors in breast cancer is associated with interaction between oestrogen receptor-alpha and progesterone receptor-b
Menée à l'aide d'une lignée cellulaire de cancer mammaire et d'explants tumoraux, puis menée auprès d'une cohorte de 229 patientes atteintes d'un cancer du sein ER- HER2- avec envahissement des ganglions axillaires, cette étude met en évidence l'intérêt de mesurer la fréquence d'interaction entre le récepteur alpha des estrogènes et le récepteur bêta de la progestérone pour prédire la survie sans récidive chez les patientes recevant un traitement adjuvant par inhibiteur d'aromatase
Background : Recent pre-clinical studies indicate that activated progesterone receptor (PR) (particularly the PR-B isoform) binds to oestrogen receptor-
α (ER) and reprogrammes transcription toward better breast cancer outcomes. We investigated whether ER and PR-B interactions were present in breast tumours and associated with clinical parameters including response to aromatase inhibitors.
Methods
:
We developed a proximity ligation assay to detect ER and PR-B (ER:PR-B) interactions in formalin-fixed paraffin-embedded tissues. The assay was validated in a cell line and patient-derived breast cancer explants and applied to a cohort of 229 patients with ER-positive and HER2-negative breast cancer with axillary nodal disease.
Results
:
Higher frequency of ER:PR-B interaction correlated with increasing patient age, lower tumour grade and mitotic index. A low frequency of ER:PR-B interaction was associated with higher risk of relapse. In multivariate analysis, ER:PR-B interaction frequency was an independent predictive factor for relapse, whereas PR expression was not. In subset analysis, low frequency of ER:PR-B interaction was predictive of relapse on adjuvant aromatase inhibitor (HR 4.831, p
= 0.001), but not on tamoxifen (HR 1.043, p = 0.939).
Conclusions : This study demonstrates that ER:PR-B interactions have utility in predicting patient response to adjuvant AI therapy.
British Journal of Cancer , résumé, 2018