Nye Pilot Project Summary

This pilot project aims to address the feasibility of a translational mouse model paired with an in-human pre-surgical window of opportunity clinical trial designed to identify a biomarker signature of non-response to Duavee® (bazedoxifiene and conjugated estrogen) in ductal carcinoma in situ (DCIS). With success, this model could be expanded to evaluate alternative drug therapies and allow for more expedient identification of drugs that have fewer toxicities and improved quality of life compared to standard chemoprevention and reduce the risk of invasive breast cancer.

The mouse model, known as mouse-intraductal or MIND model requires cells from patient with DCIS acquired from a breast biopsy that are injected into the immuno-compromised mouse mammary glands and allowed for progression of the human tumor within a mouse duct. The human study will involve postmenopausal women (participants) to be treated with BZA + CE in the pre-operative setting, for two to four weeks prior to definitive surgery. The paired mice (paired to the human that the DCIS cells were acquired from) in the MIND model will be injected with patient derived DCIS cells. Three months following the intraductal injection of cells, mice will be treated with BZA + CE for 3 months. At the end of 6 months, the mice will be assessed for the development of invasive disease, which would will be considered a nonresponse to the drug therapy. RNA sequencing will be done on mouse breast tissue to identify a signature of non-response. The identified signature will then be assessed in the paired human biopsy breast tissue and validated based on the ability to predict non-response in human tissue (change in Ki67 labeling index).

Aim 1: To establish feasibility of enrolling post-menopausal woman to a translational paired mouse and human study of Duavee® in DCIS.

Aim 2: To establish feasibility of the model to supply adequate tissue for biomarker assessment for a signature of DCIS tumor non-response to Duavee® in human breast tissue guided by findings in the paired mouse model.