PacRim7 7th PacRim Meeting Poster Presentations (1) (52 abstracts)
Recent pre-clinical studies indicate that activated progesterone receptor (PR) (particularly the PR-B isoform) binds to oestrogen receptor-α (ER) and reprograms transcription toward better breast cancer outcomes. We investigated whether ER and PR interactions were present in breast and endometrial tumours and associated with clinical parameters including response to endocrine treatments. We developed a proximity ligation assay to detect ER and PR interactions in formalin-fixed paraffin-embedded tissues. The assay was validated in a cell line and patient-derived breast cancer explants. The assay was applied to a cohort of 229 patients with ER-positive and HER2-negative breast cancer with axillary nodal disease and another cohort of 100 patients with early-stage endometrioid adenocarcinoma treated with a levonorgestrel-releasing intrauterine device (Mirena). In breast cancer, a 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). Results of the endometrioid adenocarcinoma cohort are to be detailed during the meeting. This study demonstrates that ER:PR-B interactions have utility in predicting patient response to adjuvant AI therapy in breast cancer. ER and PR interactions are potentially associated with response to progestogen in endometrial cancer.
17 Mar 2019 - 20 Mar 2019