Dose-dense therapy in the treatment of early-stage breast cancer: An overview of the data

Breast cancer represents a significant public health burden with > 200,000 new cases diagnosed in the United States each year. Although a significant proportion of these new diagnoses represent early-stage disease, many of these women will eventually experience a distant relapse and ultimately die of complications of metastatic breast cancer. Consequently, innovations in adjuvant treatment strategies are critical as we strive to further optimize outcomes. One such innovation, the dose-dense approach, is intended to specifically optimize the administration of standard chemotherapy regimens. Specifically, models of tumor growth and response, based on the Norton-Simon hypothesis, were translated into regimens which aim to increase tumor cell kill by decreasing the time intervals between treatments. This strategy, fully evaluated with doxorubicin/cyclophosphamide and paclitaxel in Cancer and Leukemia Group B 9741, demonstrated significant benefits compared with conventionally scheduled adjuvant chemotherapy. Dose density has since been applied to a number of other chemotherapy regimens and evaluated in clinical trials. An overview of the pivotal dose-dense trials will be reviewed herein.