PURPOSE - The aim of this study was to determine the safety and pathologic response rates following neoadjuvant paclitaxel and radiation in patients with stage II/III breast cancer and to evaluate the use of sequential biopsies to allow an in vivo assessment of biological markers as potential predictive markers of response to this regimen.
PATIENTS AND METHODS - Patients with high-risk, operable breast cancer were treated with three cycles of paclitaxel 175 mg/m2 every 3 weeks, followed by twice-weekly paclitaxel 30 mg/m2 and concurrent radiation. Core biopsies were obtained at baseline and 24 to 72 hours after the first cycle of paclitaxel. After completing neoadjuvant treatment, patients underwent definitive surgery. The primary end point was pathologic complete response, which is defined as the absence of any invasive cancer at surgery. Potential markers of therapeutic response were evaluated including markers of proliferation, apoptosis, p21, HER2, estrogen receptor, and progesterone receptor status.
RESULTS - Of the 38 patients enrolled, 13 (34%) had a pathologic complete response. There was no significant difference in baseline Ki-67 between responders (35%) and nonresponders (28%; P = 0.45). There was also no significant change in Ki-67 following paclitaxel administration. Despite this lack of immunohistologic change in proliferative activity, baseline mitotic index was higher for patients with pathologic complete response over nonresponders (27 versus 10, P = 0.003). Moreover, the increase in mitotic index following paclitaxel administration was associated with pathologic complete response.
CONCLUSIONS - Neoadjuvant paclitaxel/radiation is effective and well tolerated. Tumor proliferation at baseline and response to chemotherapy as measured by mitotic activity may serve as an important indicator of pathologic response to neoadjuvant paclitaxel/radiation.