Chemotherapy is traditionally initiated six weeks postoperatively. This allows the tissue time to heal prior to the immunosuppression associated with chemotherapy. Chemotherapy was historically reserved for patients with a poor prognosis. This included patients with greater than 4 positive nodes, primary tumors greater than 4 cm, a grade III tumor, or any tumor with lymphatic or vascular invasion. All of these imply systemic spread of tumor. Neoadjuvant chemotherapy is used in women who desire breast conservation but have large primary tumors. Preoperative chemotherapy has been shown to decrease the size of the primary tumor and, also, the incidence of positive nodes with no change in systemic recurrence.1
Chemotherapy can be divided into cytotoxic, hormonal, and molecular. Cyto-toxic chemotherapy is the classic chemotherapy and includes four main drugs. The classic therapy is CMF (cyclophosphamide, methotrexate, and 5-fluorouracil). Adriamycin (doxorubicin) is sometimes added or substituted (Table 9.6).
Tamoxifen is the first hormonal chemotherapy drug and is used to block estrogen receptors.2 This drug historically was used for tumors that are estrogen or progesterone receptor positive. Now, tamoxifen is used in women that are receptor positive or negative for prophylaxis against a new breast cancer. This is used after cytotoxic chemotherapy. Tamoxifen functions to put the cancer cells in G0 phase of cell division by blocking the estrogen receptor. Either used as prophylaxis against further
Table 9.6. Chemotherapeutic agents used in breast cancer
Alkylating agent that stops DNA replication
Acid analogue that inhibits DNA replication
Antimetabolite to inhibit DNA synthesis DNA antimetabolite that the exact function is unknown, but intercalates between DNA base pairs
Microtubule stabilizer preventing malignant cells from completing mitosis
Nausea and vomiting Cardiomyopathy with a cumulative effect. Limited lifetime dose secondary to this side effect.
Peripheral neuropathy cancer or in receptor positive patients, no increased benefit has been seen with more than 5 years use. The side effect is an increased risk of uterine cancer secondary to the estrogen receptor blockade/stimulation.
Aromatase inhibitors are a new hormonal chemotherapy that serves to decrease end estrogen production. Aromatase is the enzyme that makes estrogen in a final biochemical pathway.
Molecular chemotherapy is being developed and one drug has been FDA approved. Herceptin is a monoclonal antibody to HER-2-neu. HER-2-neu is an epidermal growth factor receptor that has overexpression in poor prognosis breast cancer. This has been shown to decrease progression of disease in metastatic breast cancer.
1. Fisher B, Brown A, Mamounas E et al. Effect of preoperative chemotherapy on local-regional disease in women with operable breast cancer: Findings from national surgical adjuvant breast and bowel project b-18. J Clin Onc 1997; 15:7:2483-2493.
2. Early breast cancer trialists' collaborative group, tamoxifen for early breast cancer: An overview of the randomised trials. Lancet 1998; 351:1451-1467.
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