Neoadjuvant (or preoperative) chemotherapy is being increasingly used for the treatment of breast cancer. Response to neoadjuvant chemotherapy may convert an inoperable breast cancer to an operable tumor. By downsizing the tumor, neoadjuvant chemotherapy also increases the possibility of breast-conserving surgery in a larger number of patients1,2 (Fig. 85-1A). In addition, in patients who have operable breast cancer at the onset, the delivery of neoadjuvant chemotherapy allows for excisions of smaller volumes of breast tissue. Indeed, this was shown in a study by Boughey et al3 in which patients treated with neoadjuvant therapy were compared with patients who underwent adjuvant chemotherapy. For patients who had an initial tumor size greater than 2 cm, neoadjuvant chemotherapy was found to allow for significantly smaller volumes of breast tissue to be excised (113 cm3 vs 213 cm3, p = 0.004). In this study, the delivery of neoadjuvant chemotherapy did not alter the reexcision rate or the number of operations performed in the 2 groups.
Neoadjuvant chemotherapy for women with operable breast cancer. Comparison of preoperative versus postoperative chemotherapy. A. Locoregional treatment (mastectomy rate). B. Overall survival. C. Disease-free survival. (Reproduced, with permission, from Mieog JS, van der Hage JA, van de Velde CJ. Preoperative chemotherapy for women with operable breast cancer. Cochrane Database Syst Rev. 2007:CD005002.)
Another rationale for neoadjuvant systemic therapy is that this allows for the immediate treatment of micrometastases; however, this has not been associated with an increase in survival in most trials to date (Figs. 85-1B and 85-1C). In contrast, a major advantage is that tumor response to chemotherapy is a strong predictor of outcome. Thus neoadjuvant systemic therapy can be used as an in vivo assay of systemic therapy efficacy. This, in theory, can allow for testing of new therapy regimens in the neoadjuvant setting, allowing for shorter and smaller trials to be conducted using chemotherapy response as the primary end point. In addition, the neoadjuvant setting allows the opportunity to identify biomarkers that can predict response as well as identify pharmacodynamic markers of response, that is to say, markers that can change within the primary tumor with the administration of chemotherapy, which can be an early molecular signal of therapy activity. Although the standard of care at this point has been to not deliver any further therapy in patients who have received a full course of neoadjuvant chemotherapy even if they have significant residual disease, there is now increasing interest in clinical trials of further therapy based on the residual cancer burden, as well as the molecular phenotype of the residual disease for subsequent treatment planning.
Neoadjuvant chemotherapy does, ...