Adjuvant systemic therapy for early breast cancer.

Breast cancer-specific mortality has declined over the last two decades as a result of the introduction of screening programmes and advances in adjuvant systemic therapy. The most notable progress has been achieved in the case of Her2-positive disease, following the introduction of trastuzumab, a humanized monoclonal antibody targeting the extracellular domain ofHer2. Indeed, addition of trastuzumab to chemotherapy for a total duration of 1 year increases progression-free survival (PFS) as well as overall survival (OS) compared with chemotherapy alone. In hormone receptor-positive disease, treatment with aromatase inhibitors (AIs) prolongs PFS compared with tamoxifen, and in some clinical trials they have been found to increase OS also. Chemotherapy remains the mainstay of treatment for patients with triple-negative disease and also plays a role in Her2-positive and high-risk hormone receptor-positive tumours. Although, overall, only limited progress has been achieved in this field, most trials suggest that the introduction of taxanes has resulted in improved outcomes. Dose-dense chemotherapy is superior to older adjuvant regimens comprising 3-weekly administration of paclitaxel, while high-dose chemotherapy with autologous stem cell support currently has no place in the treatment of breast cancer. Neoadjuvant chemotherapy increases the rate of breast-conserving surgeries; importantly, the pathological complete remission (pCR) rate has been identified as a surrogate for improved OS in hormone receptor-negative patients. Thus, clinical trials have aimed to increase pCR rates by addition of further cytotoxic substances or biologicals such as trastuzumab, lapatinib or bevacizumab. However, the optimum treatment strategy for hormone receptor-negative patients without pCR remains elusive. This review discusses recent developments and open questions in the field of adjuvant systemic therapy for early breast cancer.