Chemosensitivity based approach of neoadjuvant chemotherapy with doxorubicin plus cyclophosphamide or docetaxel plus cyclophosphamide for operable breast cancer

AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA 3619 BACKGROUND: Active nonanthracycline-containing regimens are emergingfrom clinical trials of breast cancer. US oncology group demonstrated that docetaxel plus cyclophosphamide (TC) was associated with a superior disease free survival compared with a standard adjuvant treatment of doxorubicin plus cyclophosphamide (AC). There is also growing evidence that gene expressions may be markers for anthracycline or taxane sensitivity. AIM: In this pilot study, we attempt to demonstrate an improved response by chemosensitivity-based approach with AC or TC over a standard regimen of AC. METHODS: The study included 19 women with operable breast cancer with lymph node metastasis. In addition to routine histological study including ER/PgR status with core needle biopsy specimens before treatment, gene expressions of HER2, topoisomerase II α (TOPO IIα), Cyp3A4, class III β tublin, p53 and ki67 were examined immunohistochemically. According to sensitivity results, patients received chemotherapy four cycles of either standard-dose AC (60 and 600 mg/m2 q3w, respectively) or TC (75 and 600 mg/m2 q3w, respectively). AC was chosen for cases with higher expressions of HER2/TOPO IIα and/or Cyp3A4/classIII β tublin, while TC for cases with the opposite patterns of expressions. When pathological complete response including near pCR (only focal residual tumor cells) (pCR) was not achieved by an initial treatment, crossover to the alternative treatment was recommended. Primary endpoint was pCR rate of this study. Secondary endpoint was to compare pCR rates between AC and TC. The projected pCR rate of this study was estimated to be more than 9% based on previous studies with AC. RESULTS: At present, analysis was completed for 9 cases for AC, and 10 cases for TC. The pCR rate of this study was 21 %. That of AC and TC was 11% and 33 %, respectively. CONCLUSIONS: TC demonstratedsuperior efficacy compared with AC, providing significant higher pCR rate. The examination of these gene expressions may not be sufficient to predict chemosensitivity, especially for AC.