Proliferating Fraction During Neoadjuvant Chemotherapy of Primary Breast Cancer in Relation to Objective Local Response and Relapse-free Survival

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Abstract
In women with inoperable primary breast cancer or large T2 tumors, preoperative chemotherapy may induce tumor shrinkage, facilitate surgery and possibly improve survival. However, at present there are no reliable tumor cell parameters to predict which patients will benefit from preoperative chemotherapy. The aims of this study were to analyze the utility of tumor cell proliferation as assessed by Ki-67 staining in fine-needle aspirates from primary breast carcinomas to predict initial response to neoadjuvant chemotherapy as well as recurrence-free survival. The study comprised 51 women with primary breast cancer who received 3-4 courses of CEF (cyclophosphamide, epirubicin, 5-fluorouracil) as neoadjuvant chemotherapy. Tumor cells were procured through fine-needle aspiration biopsy prior to treatment. A second biopsy was performed before the second course of therapy in 33 women. Twenty-nine women (56%) experienced an objective local response after neoadjuvant treatment. During a median follow-up period of 39 months, 21 women (41%) developed disease recurrence. A decrease of more than 25% in proliferating fraction after the first course of chemotherapy correlated significantly with a decreased risk of disease recurrence (p = 0.033) but showed no significant correlation with local objective response. A multivariate analysis revealed that the decrease in proliferating fraction significantly (p < 0.05) added prognostic information to that of involved lymph nodes. These results suggest that changes in proliferating fraction as assessed by Ki-67 staining in fine-needle aspirates during preoperative chemotherapy may be of value in selecting postoperative adjuvant systemic treatment.

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