Molecular markers predicting response to preoperative
chemotherapy would be of major clinical relevance in
breast cancer. Therefore, we studied the relationship between the expression of
cell cycle regulatory proteins and clinical outcome in
breast cancer patients receiving preoperative
chemotherapy. Expression of p2lWaf1, p27KiP1, p53,
cyclin D3 and Ki-67 was determined in
breast carcinomas by means of immunohistochemistry both prior and after preoperative
chemotherapy. Expression data were compared with both clinical parameters and response to preoperative
chemotherapy with either
cyclophosphamide/
methotrexate/
5-fluorouracil (CMF, n = 29) or
epirubicin/
docetaxel (ED, n = 36). In paired samples before and after preoperative
chemotherapy, the percentage of p21Waf1, p27Kip1, p53 and
cyclin D3 positive nuclei of
tumor cells in postchemotherapy specimens was significantly higher than the percentage in prechemotherapy samples but no change in Ki-67 expression was observed. High Ki-67 expression (p = 0.02), negative
estrogen receptor status (p = 0.01) and negative
progesterone receptor status (p = 0.04) were associated with complete pathologic response to
chemotherapy, whereas the other markers did not predict response. In conclusion, expression levels of p21Waf1, p27Kip1, p53 and
cyclin D3 significantly increased after preoperative
chemotherapy in
breast carcinomas but only high Ki-67 expression, negative
estrogen receptor status and negative
progesterone receptor status were associated with complete pathologic response to preoperative
chemotherapy.