Breast cancer is the most common non-skin cancer affecting women worldwide. In the United States, over 90% of tumors are diagnosed as either in situ or localized to the breast or regional lymph nodes. Surgical treatment and adjuvant radiotherapy play an important role in loco-regional treatment of early stage breast cancer. Systemic adjuvant therapy is targeted towards isolated circulating and/or disseminated tumor cells to prevent systemic recurrence. This review will describe the diverse tumor biology of human breast cancer and how it influences decisions with regard to the use of adjuvant therapies. J. Surg. Oncol. 2011;103:619–626. © 2011 Wiley-Liss, Inc.