Assessment of a Human Proliferation Signature to Predict Endocrine Blockade Therapy Response in an Animal Model of ER+ Breast Cancer

Breast cancer (BrCa) is the most frequently cancer diagnosed in women in the United States. There are over 200,000 new cases per year and a death rate of over 40,000 per year. Recent studies that in ER+ breast cancer, tumor proliferation is a good prognostic indicator. Furthermore, neo-adjuvant studies have shown that proliferation can be used as predictor of response to endocrine blockade therapy. A common method to assess proliferation in breast cancer is measuring protein expression of Ki-67.  In this study, we used a combination of 10 cell cycle-regulated genes to assess proliferation in mammary tumors in Rattus norvegicus that were induced by methylnitrosourea. These were ER+ breast cancers that had been treated in the rat using several different endocrine blockade agents. We developed and validated primer sets to measure the 10 proliferation genes in the rat tumors. These were tested across 10 different rat tumors and changes in expression were correlated to therapy response.