Tamoxifen Response at Single-Cell Resolution in Estrogen Receptor-Positive Primary Human Breast Tumors

Area of Science:

• Oncology
• Genomics
• Cell Biology

Background:

• Intratumor heterogeneity in ER+/HER2- breast cancer is linked to poor response to endocrine therapy.
• Understanding cellular heterogeneity is crucial for predicting treatment efficacy.

Purpose of the Study:

• To develop a novel experimental model for measuring heterogeneity in response to tamoxifen treatment in primary breast tumors.
• To investigate tamoxifen response differences across cell types within human breast tumors.

Main Methods:

• Developed an operating room-to-laboratory pipeline for immediate processing of live breast specimens.
• Utilized single-cell workflows, including 10X Genomics, for genomic and experimental analyses.
• Treated ex vivo primary cell suspensions with tamoxifen or control media for 12 hours.

Main Results:

• Identified distinct tamoxifen-responsive and resistant subpopulations within malignant cells.
• Demonstrated cell-type-specific differences in tamoxifen response.
• Tamoxifen resistance signatures from resistant subpopulations predict poor outcomes in ER+ breast cancer cohorts.

Conclusions:

• The novel ex vivo model enables definition of responsive and resistant subpopulations in heterogeneous tumors.
• This system can lead to precise single-cell predictors of therapy response.
• The model facilitates identification of genes and pathways driving therapeutic resistance.