This study was designed to assess whether histological and biological factors of breast cancer can predict chemoresponse to specific agents. Adenosine triphosphate-based chemotherapy response assay (ATP-CRA) was employed to retrieve chemoresponse to 5-fluorouracil (5-FU), doxetaxel, doxorubicin, epirubicin, and paclitaxel in 49 patients. Tumors with high histologic and nuclear grade have higher response rate to doxorubicin (P<0.05) and palitaxel (P<0.05). Estrogen receptor (ER)-negative tumors respond well to doxorubicin (P=0.038), and progesterone receptor (PR)-negative tumors to 5-FU (P=0.039), doxetaxel (P=0.038), doxorubicin (P=0.000), epirubicin (P=0.010), and paclitaxel (P=0.003). Among the breast cancer subtypes determined by ER, PR, and HER-2 immunohistochemical stains, the HER-2+/ER- subtype has a higher response rate to doxorubicin (P=0.008). This in vitro result suggests that the combination of histologic and nuclear grade, hormone receptor, and HER-2 status can be a predictive factor of response to specific chemotherapy agents. Further in vivo study should be followed for clinical trials.
Adenosine Triphosphate/*metabolism ; Adult ; Aged ; Antineoplastic Agents/*therapeutic use ; *Breast Neoplasms/classification/drug therapy/pathology ; Doxorubicin/therapeutic use ; Drug Screening Assays, Antitumor/*methods ; Epirubicin/therapeutic use ; Female ; Fluorouracil/therapeutic use ; Humans ; Middle Aged ; Paclitaxel/therapeutic use ; Receptor, erbB-2/genetics/*metabolism ; Receptors, Estrogen/genetics/metabolism ; Receptors, Progesterone/genetics/metabolism

Antineoplastic Agents, Hormonal ; therapeutic use ; Breast Neoplasms ; classification ; drug therapy ; pathology ; surgery ; Carcinoma in Situ ; drug therapy ; pathology ; surgery ; Carcinoma, Intraductal, Noninfiltrating ; drug therapy ; pathology ; surgery ; Carcinoma, Lobular ; drug therapy ; pathology ; surgery ; Diagnosis, Differential ; Female ; Humans ; Mastectomy ; Precancerous Conditions ; drug therapy ; pathology ; surgery ; Tamoxifen ; therapeutic use

OBJECTIVETo investigate the expression of extracellular signal-regulated kinase (ERK) and its relationship with clinicopathological characteristics of breast cancer as well as the effect of preoperative chemotherapy on ERK expression.

METHODSExpression of ERK-1 and ERK-2 protein was examined by Western blot in the breast cancer and normal breast (control) tissue of 48 patients, of whom 8 had received preoperative chemotherapy of 5'-deoxy-5-fluorouridine (5'-DFUR), with distribution of ERKs protein detected by immunohistochemical method.

RESULTSExpression of ERK-1 and ERK-2 protein was increased in tumor specimen as compared with control tissue (P < 0.01). A positive correlation was observed between ERK-1 and ERK-2 (r = 0.457, P < 0.01). Protein level of ERK-1 and ERK-2 was higher in stage III patients than in stage I and stage II patients (P < 0.05). Expression of both ERK-1 and ERK-2 in the carcinoma tissue was decreased in patients who had received preoperative chemotherapy of 5'-DFUR. ERK-1 and ERK-2 proteins were mainly located in the cytoplasm.

CONCLUSIONThe hyperexpression of ERK may play an important role in the initiation and development of human breast cancer. Preoperative chemotherapy of 5'-DFUR is able to partially inhibit ERK expression.

Antimetabolites, Antineoplastic ; therapeutic use ; Breast Neoplasms ; classification ; drug therapy ; enzymology ; pathology ; Female ; Floxuridine ; therapeutic use ; Humans ; Mitogen-Activated Protein Kinase 1 ; biosynthesis ; Mitogen-Activated Protein Kinase 3 ; Mitogen-Activated Protein Kinases ; biosynthesis ; Neoplasm Staging