One of the basic principles of cancer chemotherapy is that these drugs act exclusively or mainly on cells in cycle. Estrogens have been shown to increase the fraction of breast cancer cells in cycle. Tamoxifen on the other hand, decreases the proliferative fraction and has been shown to negatively impact on the results of adjuvant chemotherapy in breast cancer when given concomitantly. A number of previous studies have attempted estrogenic recruitment of cancer cells (into cell cycle) to increase the efficacy of chemotherapy in locally advanced and metastatic breast cancer. Although some studies showed an increase in response rates in the recruitment arm, there was no benefit in time to progression or survival in any of the studies. These results may have been due to the inadequate sample size of the studies and advanced stage disease (with presumably higher fraction of inherently chemoresistant cells).

The present study is designed to test the hypothesis that estrogenic recruitment of micrometastatic disease in operable breast cancer will increase the efficacy of standard adjuvant chemotherapy after surgery. The intervention arm of the study will involve administration of short duration estrogen prior to each cycle of adjuvant chemotherapy. The end-points are disease free and overall survival.