Invasive Lobular Carcinoma Cell Lines Are Characterized by Unique Estrogen-Mediated Gene Expression Patterns and Altered Tamoxifen Response

What is it about?

Invasive lobular carcinoma (ILC) is the 2nd most common subtype of breast cancer, but the unique biology of ILC is not well understood. In particular, though most ILC tumors express the estrogen receptor (ER), ER signaling and response to anti-estrogen therapies have not been well characterized in ILC cells. This study used ILC models to examine how estrogen receptor (ER) signals and regulates gene expression specifically in ILC cells. We found that ER controls the expression of a large series of genes that are specific to ILC cells, suggesting that ER does have unique functions in ILC cells. Also, when we examined response to the anti-estrogen therapy tamoxifen, we found that one ILC cell line had innate tamoxifen-resistance. These observations together strongly suggest that ER has ILC-specific functions, and that understanding these functions may be necessary to improve anti-estrogen therapy for ILC patients.

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Why is it important?

The majority of ILC tumors (>90%) express ER; this and other biomarkers suggest that ILC patients should respond well to anti-estrogen therapy. However, retrospective studies instead showed that a subset of ILC tumors may in fact be anti-estrogen-resistant (e.g. http://www.ncbi.nlm.nih.gov/pubmed/26215945). This study provides the first mechanistic insight for why ILC may be anti-estrogen resistant, identifies a model to study this property of ILC, and provides a foundation for studies to improve ER-targeted therapies for ILC patients.