Abstract P2-09-29: Cyclin-Dependent Kinase-Based Risk Score Predicts Both Clinical and Pathological Response to Neoadjuvant Paclitaxel Followed by FEC in Early Breast Cancers
Authors: Kim SJ , Tamaki Y , Tsukamoto F , Akazawa K , Nakayama S , Torikoshi Y , Matsushima T , Gohda K , Ishihara H , Noguchi S. 
Published: April 2011

Background: We have reported that breast tumors with a high ratio of cyclin-dependent kinase (CDK) 2 to CDK 1 are associated with high tumor cell proliferation and poor clinical outcome in Japanese. In addition, we have developed risk score based on CDK2/1 ratio (CDK-RS), and have demonstrated a high risk group showed a significantly poor prognosis in Hollanders (van Nes, et al: Br J C 2009: 100: 494). The aim of the present study is to evaluate the correlation of CDK-RS with response to neoadjuvant paclitaxel followed by fluorouracil + epirubicin + cyclophosphamide (FEC) in breast cancers.

Material and Methods: Of 131 primary breast cancer patients (age: 25-73y, mean: 51.7y), 126 were treated with paclitaxel (80 mg/m2, weekly) for 12 cycles followed by FEC (500/75/500 mg/m2, q3w) for four cycles and 5 were treated with paclitaxel-monotherapy (5 — 29 cycles) in the NAC or primary chemotherapy setting. Frozen tumor tissues were obtained from core needle biopsy before NAC, and CDK-RS was determined by the Cell Cycle Profiling (C2P) assay as previously reported. Clinical response was evaluated with MRI before NAC and after paclitaxel and FEC. Patients were classified into responders showing ≥80 % in reduction rates and non-responders showing &lt; 80 %. Pathological CR (pCR) was defined as no residual invasive foci and no axillary lymph node metastasis. Results: Patients characteristics were as follows: menopausal status: pre-47%, post-53%; Stage: II 68%, III 27%, IV 7%; Tumor size (cm): ≥5 cm 73%, &gt; 5 cm 27%; histologic grade (HG): I 16%, II 60%, III 24%; ER: (+) 56%, (-) 44%; PR: (+) 39%, (-) 61%; HER2: (+) 28%, (-) 72%. Of 131 patients, 22 (18%) attained pCR but 100 (82%) did not pCR (9 were excluded from evaluation of pathologic response because of stage IV diseases, no operations, and not available pathologic examination). In CDK-RS, 47% of 131 tumors were classified into high, 17% intermediate, and 37% low. In combination with high + intermediate risk score groups, that group had a tendency to show high HG (grade 2 or 3) (87% vs 78%), ER negativity (49% vs 35%), and PR negativity (65% vs 54%) compared with a low risk group, but their differences were not statistically significant. Tumors in the high + intermediate group were significantly more likely to show clinical response after the completion of not only paclitaxel (52% vs 27%, p=0.006) but also FEC (75% vs 52%, p=0.011) as well as to show pCR (24% vs 9%, p=0.037) compared with a low risk score group. In univariate analysis, CDK-RS showed a significant correlation with pCR (high + intermediate vs low, Odds ratio 4.03, 95%CI 1.03 — 10.3, p=0.045).

Discussion: CDK-RS in tumor samples before NAC is significantly associated with clinical and pathological response to paclitaxel followed by FEC. Thus CDK-RS seems to be a novel and useful predictive factor for paclitaxel — FEC in breast cancers.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-09-29.