Breast cancer is the most common malignancy among American women. Due to increased screening, the majority of patients present with early-stage breast cancer. The Oxford Overview Analysis demonstrates that adjuvant hormonal therapy and polychemotherapy reduce the risk of recurrence and death from breast cancer. Adjuvant systemic therapy, however, has associated risks and it would be useful to be able to optimally select patients most likely to benefit. The purpose of adjuvant systemic therapy is to eradicate distant micrometastatic deposits. It is essential therefore to be able to estimate an individual patient's risk of harboring clinically silent micrometastatic disease using established prognostic factors. It is also beneficial to be able to select the optimal adjuvant therapy for an individual patient based on established predictive factors. It is standard practice to administer systemic therapy to all patients with lymph node-positive disease. However, there are clearly differences among node-positive women that may warrant a more aggressive therapeutic approach. Furthermore, there are many node-negative women who would also benefit from adjuvant systemic therapy. Prognostic factors therefore must be differentiated from predictive factors. A prognostic factor is any measurement available at the time of surgery that correlates with disease-free or overall survival in the absence of systemic adjuvant therapy and, as a result, is able to correlate with the natural history of the disease. In contrast, a predictive factor is any measurement associated with response to a given therapy. Some factors, such as hormone receptors and HER2/neu overexpression, are both prognostic and predictive. The Oncologist 2004;9:606-616

Background NSABP B-35 is a phase III trial comparing anastrozole (A) to tamoxifen (T) for breast cancer-free interval (BCFI), defined as time from randomization to any breast cancer event: local, regional, distant, or contralateral, invasive or DCIS. Methods Postmenopausal women with hormone-positive DCIS treated by lumpectomy with clear resection margins and whole breast irradiation were randomized to receive either 20mg/day T or 1mg/day A (blinded) for 5 years. Stratification was by <60 versus ≥60 years. Findings From 1/6/2003–6/15/2006, 3,104 patients were entered and randomized. As of 2/28/15, follow-up information was available on 3,083 patients for OS and 3,077 for all other disease-free endpoints, with median follow-up of 9 years. There were 212 BCFI events, 122 in the T group and 90 in the A group (HR, 0.73; 95% CI, 0.56–0.96; p=0.0234). 10-year estimates for BCFI were 89.1% (95% CI, 86.8–91.0) for T and 93.1% (95% CI, 91.5–94.5) for A. A significant time-by-treatment interaction (p=0.0410) became evident later in the study. There was a significant interaction between treatment and age group (p=0.0379); A is superior only in women <60 years. There were 495 DFS events: 260 in the T group, 235 in the A group (HR, 0.89; 95% CI, 0.75–1.07; p=0.21). 10-year DFS estimates were 77.9% (95% CI, 75.0–80.6) for T and 82.7% (95% CI, 80.4–84.7) for A. There were 186 deaths: 88 in the T group, 98 in the A group (HR, 1.11; 95% CI, 0.83–1.48; p=0.48). 10-year OS estimates were 92.1% (95% CI, 90.1–93.7) for T, 92.5% (95% CI, 90.8–93.9) for A. Eight deaths were due to breast cancer in the T group and five in the A. There were 69 cases of invasive breast cancer in the T group and 43 in the A group (HR, 0.62; 95% CI, 0.42–0.90; p=0.0123). A significant reduction in contralateral breast cancers with A (HR, 0.64; 95% CI, 0.43–0.96; p=0.0322) was identified. Interpretation Anastrozole provided a significant improvement compared to tamoxifen for BCFI, primarily in women <60 years. Funding US NCI; AstraZeneca Pharmaceuticals LP.