Adjuvant Systemic Therapy

Despite advances in local therapy, a substantial proportion of women with early-stage disease will not be cured with local treatment alone. Ten-year disease-free survival rates for patients treated with radical mastectomy alone are shown in Table 33.7. Despite optimal local therapy, many women develop distant disease over time, presumably because micrometastases have already spread to other parts of the body from the original breast tumor. Adjuvant systemic therapy attempts to eradicate this subclinical disease and improve disease-free and overall survival. The principal options for adjuvant therapy are hormonal treatment (tamoxifen) and cytotoxic chemotherapy.

Well over 100 randomized clinical trials examining adjuvant therapy for early-stage breast cancer have been conducted worldwide. Large meta-analyses of adjuvant trials were updated in 1995. The most recent publication of the Early Breast Cancer Trialists' Collaborative Group included 124 randomized trials beginning before 1990 from which primary data could be obtained, including data on more than 67,000 women.

In general, tamoxifen treatment substantially reduced proportional mortality at 10 years by up to 26% among all women with estrogen receptor-positive (ER-positive) and ER-unknown tumors. Importantly, tamoxifen had essentially no impact on disease-free and overall survival in women whose tumors were estrogen receptor-negative. Adjuvant chemotherapy also substantially reduced risk of recurrence and mortality in all age groups. Among women under 50, chemotherapy results in an proportional reduction in mortality of 15% to 27%, whereas among women age 50 or older, the proportional reduction was of the order of 8% to 14%. Thus, overall, adjuvant chemotherapy and hormonal treatments result in significant improvements in disease-free and overall survival (Figure 33.2). Unfortunately, despite adjuvant therapy, a significant number of women will relapse and ultimately die of breast cancer. Thus, decisions about adjuvant therapy should be based on the risk of recurrence, and proportional risk reduction with specific therapies balanced with toxicities of therapy, life expectancy, and patient preferences.