Integration of Systemic Chemotherapy in the Management of Primary Breast Cancer

Breast cancer cells can metastasize early in the development of primary tumors. Adjuvant chemotherapy improves disease-free survival and overall survival (OS) in patients with early-stage breast cancer, both in premenopausal and postmenopausal women. Tamoxifen improves OS in patients whose tumors are estrogen-receptor-positive, regardless of age. Although the relative risk reduction with these interventions is the same for all patients, the absolute benefit is more prominent in patients at the highest risk of relapse. All patients with involved lymph nodes should receive adjuvant chemotherapy if no contraindications occur. In patients with negative lymph nodes, adjuvant chemotherapy is recommended if the invasive tumor is moderately or poorly differentiated, the tumor size is larger than 1 or 2 cm, or hormone receptors are negative. Other prognostic and predictive indicators of response to chemotherapy and hormonal therapy remain investigational. Models that combine several factors to determine a patient's risk of relapse and death are presented. Neoadjuvant chemotherapy in conjunction with radiation therapy and surgery is the treatment of choice for patients with locally advanced breast cancer. Recently, this approach has been extended to patients with small, operable tumors. Neoadjuvant chemotherapy can downstage tumors effectively, leading to improved cosmetic results and possibly to a reduction in local recurrence rate. Another advantage of neoadjuvant therapy is the in vivo assessment of tumor sensitivity to chemotherapy, which allows optimization of available therapeutic agents. One disadvantage of neoadjuvant chemotherapy is that preoperative treatment causes an alteration of information regarding lymph node status prior to systemic treatment. Although the optimal chemotherapy regimen has not been established, doxorubicin-containing regimens are considered superior to non-doxorubicin-containing regimens. The role of high-dose chemotherapy is not well defined in the adjuvant setting and remains investigational. The taxanes paclitaxel and docetaxel are moving rapidly from the metastatic setting to the adjuvant setting. A better understanding of the biology of breast cancer is providing molecular tools to study novel treatment approaches. Oncogenes and tumor suppressor genes are emerging as important indicators of response to chemotherapy. These molecules, in turn, become targets for therapy. Novel agents under development are presented.