The goal of adjuvant systemic therapy for early-stage breast cancer is to eliminate micrometastatic disease, thus preventing future recurrences. Adjuvant systemic therapy, chemotherapy, targeted therapy, and/or endocrine therapy, has led to a substantial decline in breast cancer mortality in women with operable breast cancer. Although chemotherapy can be effective in preventing distant failure, not all patients benefit. Many patients would remain disease free without therapy, and others would relapse despite treatment. The decision to use adjuvant chemotherapy involves a careful assessment of its benefits and potential risks. New insights into the biology of breast cancer have provided improved tools to predict more accurately the benefits of chemotherapy in a given patient, thus allowing chemotherapy to be used in patients who most likely will benefit and sparing those who are less likely to benefit. This chapter focuses on adjuvant systemic chemotherapy; the benefit of targeted therapy and endocrine therapy are detailed elsewhere in this text.
The Early Breast Cancer Trialists' Collaborative Group (EBCTCG) has provided key insights about the benefits of adjuvant chemotherapy. The EBCTCG was formed to perform meta-analyses of randomized trials in the adjuvant setting and has been updated approximately every 5 years. The 2000 Overview Analysis (published in 2005) reaffirms the role of adjuvant chemotherapy in the treatment of early-stage breast cancer.1 This analysis involved 28,764 women treated in 60 trials that randomized patients to combination chemotherapy versus no chemotherapy and demonstrated a significant improvement in both the rate of recurrence (relative risk [RR]: 0.77) and breast cancer mortality (RR: 0.83). The relative and absolute risk reductions for both recurrence and death from adjuvant chemotherapy were similar in women with node-negative or node-positive disease, although the absolute benefits were greater in women with node-positive disease. The reduction in risk of recurrence with chemotherapy is seen within the first 5 years after randomization and is maintained at the 10- and 15-year time points.
The absolute benefit of adjuvant chemotherapy in a given patient requires knowledge of that patient's baseline risk of recurrence as well as the expected relative risk reduction from chemotherapy. A patient's baseline recurrence risk is a function of both the anatomic extent of disease (ie, tumor size and lymph node status) and the molecular characteristics of the tumor (ie, tumor grade and hormone receptor [HR] and human epidermal growth receptor 2 [HER-2] status). The RR reduction from chemotherapy (ie, a tumor's sensitivity to chemotherapy) appears to be largely based on the molecular characteristics of the tumor, independent of anatomic features, as discussed later.
Considering a patient's baseline risk and the relative benefit from chemotherapy identifies groups of patients with markedly different benefits from chemotherapy. Patients who have high baseline risk and chemo-sensitive cancers receive the greatest absolute benefit from chemotherapy, whereas those with low baseline risk and relatively chemo-insensitive cancers receive the least benefit from chemotherapy. Those patients with high baseline risk and relatively chemo-insensitive cancers and those with low baseline risk and ...