Neoadjuvant Taxotere

Systemic chemotherapy for operable breast cancer significantly decreases the risk of relapse and death. However, it is not possible to identify those patients at the outset who are likely to respond to adjuvant treatment and which type of treatment should be used. Adjuvant treatment given before surgery (neoadjuvant therapy) has a number of theoretical advantages in breast cancer, including a reduction in the requirement for mastectomy. Access to the primary tumor during early treatment allows for in vivo testing for change in molecular markers by repeat biopsies that may occur with successful treatment. Established prognostic factors like tumor size and nodal involvement are important indicators for breast cancer relapse and survival but have not been shown to be predictive of sensitivity to treatment. Estrogen receptor (ER) and progesterone receptor (PgR) expression predict for response to tamoxifen and endocrine treatment. However, predictive markers for chemotherapy are not established. Overexpression of c-erbB-2 has been associated with decreased response to CMF chemotherapy (cyclophosphamide, methotrexate, and 5-fluorouracil) in most studies. Accumulation of aberrant protein expressed by the mutated tumor suppressor gene p53 product may be associated with relative resistance to cytotoxic therapy. Tissue growth kinetics are determined by the balance between programmed cell death (apoptosis) and cell proliferation, and any alteration between the two may be regarded as a key element for the uncontrolled growth of malignant tumors. In vitro experiments suggest that many anti-cancer agents achieve their effect by inducing apoptosis. Mechanisms that suppress this process may, therefore, be important in the development of intrinsic and acquired chemotherapy resistance. A clinical study has reported an increase in labeled apoptotic leukemic cells during treatment. In breast cancer biopsy specimens, chemotherapy was found to induce apoptosis within the first 24 hours of treatment. Measurement of biological molecular markers before and after exposure may, therefore, allow for early prediction of the likelihood of response to systemic therapy. Preoperative chemotherapy has been shown to result in changes in biomarkers, and these changes, when correlated with tumor response, may be early predictors of clinical outcome. New treatment strategies are needed to improve the clinical outcome in breast cancer patients at high risk of recurrence. Even with the best present combination chemotherapy, radiotherapy, and surgery, disease recurrence and death is at least 60% in this population. Thus, new strategies are needed to improve survival. Recent advances that may improve clinical outcome include the use of taxoids (paclitaxel and docetaxel), a new class of cytotoxic agents, with reported higher response rates than standard anthracycline-based chemotherapy.