Malignant Neoplasm of Female Breast Clinical Trial
Official title:
Differential Gene Regulation During Neoadjuvant Therapy Trial of Epirubicin/Cyclophosphamide (EC) vs Docetaxel/Capecitabine (DX) Regimens in Patients With Large ER-positive and ER-negative Breast Cancers: A Randomized Phase II Trial.
A primary objective of this study is to evaluate the in vivo response of tumor to
chemotherapy through gene microarray analysis. Neoadjuvant treatment allows the unique
opportunity to observe the in vivo effects of cytotoxic therapy on gene expression in tumor
tissue. The investigators plan to evaluate several different questions by comparing gene
profiles in different phases of treatment in this study. These are outlined below.
Hypotheses
1. Chemotherapy enriches for tumor cell populations that have enhanced resistance and
survival mechanisms. These mechanisms will in part be identifiable through changes in
gene expression profiles pre vs. post treatment.
2. Use of two distinct chemotherapy selection pressures, for example a DNA-damaging regimen
(epirubicin and cyclophosphamide) or a mitotic spindle/metabolic targeted regimen
(docetaxel and capecitabine), will allow for the identification of a smaller set of
genes associated to resistance and survival mechanisms of broad importance.
3. Genes associated with enrichment for resistance and survival mechanisms will not be
present in large amounts pretreatment in tumors destined for complete pathologic
response.
The clinical outcomes of breast cancer treatment are remarkably similar regardless of the
regimen used, even though the individual drugs may differ substantially in mechanisms of
action. We are interested in identifying a set of genes that may be associated with breast
cancer cell survival following selection by chemotherapy. We intend to use two different
selection pressures (different chemotherapy regimens with different mechanisms of action) in
order to focus on those genes that are regulated similarly in response to either regimen.
Neoadjuvant chemotherapy is in common use for locally advanced breast cancers. Although it
does not yet appear to impart a survival advantage, it does enhance the likelihood of breast
conserving surgery and also provides important prognostic information. Taxotere appears to
add significantly to pathologic complete responses when added to doxorubicin and
cyclophosphamide alone. The combination of capecitabine and docetaxel was superior to
docetaxel alone in metastatic disease. Many investigators are interested in incorporating
this regimen for the treatment of earlier stages of breast cancer.
;