Abstract
Adjuvant treatment for early breast cancer is an evolving field. Since the advent of the initial cyclophosphamide, methotrexate and 5-fluorouracil (CMF) regimens, which reduced risk for recurrence and death, anthracyclines and subsequently taxanes were added to the cytotoxic armamentarium for use sequentially or in combination in the adjuvant setting. The efficacy and toxicity of each chemotherapy regimen must be viewed within the context of host co-morbidities and the specific biologic phenotype of the tumor. In the era of mammographic screening, small, node-negative breast cancer is the most frequent presentation of the disease. Patient selection for adjuvant chemotherapy has become a key issue. Traditional prognostic factors continue to be of value in determining the risk for relapse, but new and sophisticated genomic tools (such as Oncotype Dx® and Mammaprint®) are now available and may improve our ability to select patients. For those patients who do require adjuvant chemotherapy, the 'one size fits all' paradigm should never again feature in the treatment of early breast cancer, following the important insights yielded by biomarker research to identify those who will benefit the most from a particular drug. In this review we focus on some of the current controversies and potential future steps in adjuvant chemotherapy for treatment of early breast cancer.
Highlights
Adjuvant systemic therapies were originally developed in an attempt to eradicate residual micrometastatic disease immediately after local control, in order to reduce the risk for cancer recurrence and death
During the late 1960s the earliest clinical trials in the field began to evaluate the biologic concept of adjuvant chemotherapy in node-positive breast cancer, determining the effects of various chemotherapy regimens compared to observation after surgery to remove the primary tumor [3]
In this review we address current prospects of adjuvant therapy, focusing on the advances in chemotherapy with taxanes and on treatment individualization; we give attention to likely future developments involving taxanes intended to improve further outcomes in early-stage breast cancer
Summary
Adjuvant systemic therapies were originally developed in an attempt to eradicate residual micrometastatic disease immediately after local control, in order to reduce the risk for cancer recurrence and death. During the late 1960s the earliest clinical trials in the field began to evaluate the biologic concept of adjuvant chemotherapy in node-positive breast cancer, determining the effects of various chemotherapy regimens compared to observation after surgery to remove the primary tumor [3] These trials clearly demonstrated benefit from adjuvant chemotherapy in the subgroup of patients at high risk for recurrence [4,5]. The optimal duration of the adjuvant therapy was addressed in a French study (FASG-01) [13], which demonstrated that six cycles of adjuvant FEC were superior to three cycles of the same regimen in patients with operable breast cancer Based on this growing body of evidence, during the 1990s consensus emerged that six cycles of a three-drug anthracycline-containing combination was the optimal adjuvant treatment for node-positive operable breast cancer, the use of four-cycle AC and six-cycle CMF remained common practice in many institutions. The Hellenic Cooperative Oncology Group trial HE 10/97 [17] compared three cycles of epirubicin (110 mg/m2) followed by three cycles of paclitaxel (250 mg/m2) and three cycles of intensified CMF (cyclophosphamide 840 mg/m2, methotrexate 57 mg/m2, and 5-fluorouracil 840 mg/m2) versus
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