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Gene Signature May Predict Which Breast Cancer Patients Will Benefit From Tamoxifen

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Key Points

  • Loss of USP9X function in breast cancer cells resulted in tamoxifen resistance.  
  • The gene signature may be able to predict which patients with estrogen receptor–positive breast cancer will benefit from tamoxifen following surgery.
  • The gene signature could not predict treatment outcomes in patients who did not receive tamoxifen therapy, suggesting that this signature is specific to outcomes with tamoxifen treatment.

A novel approach using ChIP-seq and RNA-seq analysis in combination with RNA expression data has identified a gene called USP9X that may predict which patients with estrogen receptor–positive breast cancer will benefit from tamoxifen therapy after surgery. The gene signature the researchers identified could not predict treatment outcomes in patients who did not receive tamoxifen, suggesting that the signature is specific to outcomes with tamoxifen therapy. The study by Oosterkamp et al is published in Cancer Research.

Study Methodology and Results

To address the problem of why some patients with estrogen receptor–positive breast cancer are resistant to tamoxifen, the researchers performed a large-scale loss-of-function genetic screen in ZR-75-1 luminal breast cancer cells to identify candidate-resistance genes. They identified a gene called USP9X, whose loss of function in breast cancer cells resulted in tamoxifen resistance.

Next, the researchers identified other genes that were altered during treatment with tamoxifen, in the absence of USP9X. Then, using publicly available data sets, the researchers studied the expression of these specific genes in patients who were treated with tamoxifen after surgery and whose treatment outcomes were known. The researchers found that that the data split into two groups: one with a gene signature with a good outcome, and one with a signature showing a bad outcome, after adjuvant tamoxifen treatment.

The gene signature the researchers identified could not predict treatment outcomes in patients who did not receive tamoxifen therapy, suggesting that this signature is specific to outcomes with tamoxifen treatment.

In all, the researchers used data from about 680 patients from four different data sets to test the feasibility of the gene signature in predicting responses to tamoxifen therapy in patients with estrogen receptor–positive breast cancer.

“We are currently validating our promising results using the data from a prospective randomized controlled trial, and we expect to complete this validation by the end of this year,” René Bernards, PhD, a coauthor of the study and Professor and Head of the Division of Molecular Carcinogenesis at the Netherlands Cancer Institute in Amsterdam, said in a statement. “If this is successful, clinical implementation is a logical next step.”

Dr. Bernards is the corresponding author for the Cancer Research article.

The study was funded by the Dutch Cancer Society. The study authors reported no conflicts of interest.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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