Abstract
Breast cancer is the most common cause of cancer and cancer death worldwide. Although most patients present with localized breast cancer and may be rendered disease-free with local therapy, distant recurrence is common and is the primary cause of death from the disease. Adjuvant systemic therapies are effective in reducing the risk of distant and local recurrence, including endocrine therapy, anti-HER2 therapy, and chemotherapy, even in patients at low risk of recurrence. The widespread use of adjuvant systemic therapy has contributed to reduced breast cancer mortality rates. Adjuvant cytotoxic chemotherapy regimens have evolved from single alkylating agents to polychemotherapy regimens incorporating anthracyclines and/or taxanes. This review summarizes key milestones in the evolution of adjuvant systemic therapy in general, and adjuvant chemotherapy in particular. Although adjuvant treatments are routinely guided by predictive factors for endocrine therapy (hormone receptor expression) and anti-HER2 therapy (HER2 overexpression), predicting benefit from chemotherapy has been more challenging. Randomized studies are now in progress utilizing multiparameter gene expression assays that may more accurately select patients most likely to benefit from adjuvant chemotherapy.
Highlights
Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer death among women, accounting for 25 % of the total cancer cases (1.68 million) and 15 % of the cancer deaths (520,000) worldwide [1, 2]
Adjuvant systemic therapies reduce the risk of distant recurrence, presumably by treating micro-metastatic disease that may not be clinically evident at the time of local therapy
Localized and regionally advanced breast cancer is a potentially curative disease with local therapy alone, and adjuvant systemic chemotherapy, endocrine therapy, and anti-human epidermal growth factor receptor 2 (HER2) directed therapy substantially reduce the risk of distant recurrence and breast cancer mortality
Summary
Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer death among women, accounting for 25 % of the total cancer cases (1.68 million) and 15 % of the cancer deaths (520,000) worldwide [1, 2]. The first randomized trial evaluating adjuvant chemotherapy in breast cancer was the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-01 trial initiated in 1958, which reported in 1968 that an adjuvant alkylating agent (thiotepa) given after radical mastectomy significantly decreased recurrence rate in pre-menopausal women with four or more positive axillary lymph nodes [20]. Other reports from the Istituto Nazionale Tumori in Milan, Italy, showed that combination chemotherapy regimen called “CMF” including an alkylating agent (cyclophosphamide) and antimetabolites (methotrexate and 5-fluorouracil) significantly reduced the risk of recurrence [22], ushering in the modern age of adjuvant polychemotherapy regimens that are commonly used in clinical practice. Multiparameter gene expression assays identify subsets of patients with ER-positive disease who derive greatest benefit from adjuvant chemotherapy [29, 30] and are incorporated into evidence-based guidelines [31]
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