Purpose: Breast cancers expressing high levels of Ki-67, a nuclear marker of cell proliferation, are associated with worse outcome. Recent data from neoadjuvant studies indicate that a single measurement of the nuclear proliferation marker Ki-67 in breast carcinoma during neoadjuvant therapy is strongly predictive of long-term outcome. Secondly, recent literature data indicate that prognostic evaluation with Ki-67 may be better after pre-surgical therapy. A retrospective study from a prospectively maintained clinical database to compare the predictive and prognostic significance of biological markers, assessed before and after neoadjuvant chemotherapy, in locally advanced breast cancer, was performed. Patients and Methods: The following parameters were considered before and after chemotherapy for their relationship with treatment response and disease-free survival in 64 patients with locally advanced breast cancer: clinical stage, clinical and pathological lymph node involvement, Ki-67, estrogen receptor (ER), progesterone receptor (Pgr), Her2, tumor grade, clinical response, type of surgery performed, and number of chemotherapy cycles administered. The expression of Ki-67 was assessed using immunohistochemistry in pre-therapy tru-cut and post-therapy surgical excision specimens after neoadjuvant chemotherapy; only patients with breast tumors expressing high baseline Ki-67 (≧15%) were included in the analysis. In addition, the correlation between pre-chemotherapy biological markers and clinical and pathological response was reported. Results: Post-chemotherapy Ki-67 proliferation index decrease, pre-chemotherapy ER expression and post-chemotherapy ER expression were the only significant prognostic factors adversely influencing disease-free survival in univariate analysis. Her2 overexpression was the only factor to impact on the clinical response. Conclusions: Post-treatment Ki-67 and ER status were predictors of outcome for patients with locally advanced breast cancer and a high pre-chemotherapy proliferation index.
The relationship of changes in 3H-thymidine labelling index (TLI) induced by primary chemotherapy to tumor response and relapse rate in 36 patients with previously untreated locally advanced breast cancer (LABC) was analyzed. All patients received primary chemotherapy (3 cycles FAC), followed by mastectomy and subsequent adjuvant chemotherapy (3 FAC alternated with 3 CMF). Tumor TLI was evaluated immediately prior to primary chemotherapy and at the time of mastectomy. Median pretreatment TLI was used to discriminate between tumors with a high or low proliferative rate. Clinical objective response to primary chemotherapy was 83% in patients with high TLI and 56% for those with low pretreatment TLI (p = 0.06). Primary chemotherapy induced a > or = 50% reduction of the proliferative rate in 83% and 39% of the tumors with high and low pretreatment TLI, respectively (p = 0.006). Patients were classified into 4 groups according to TLI values both before and after primary chemotherapy: patients who remained in the high TLI group after primary FAC had the highest response rate (100%) and the lowest 2-year relapse rate (20%). These data suggest that: a) improved response to aggressive cytotoxic treatment occurs in tumors with high TLI at diagnosis; b) there is a significant correlation between TLI changes induced by primary chemotherapy and pretreatment proliferative activity; c) patients who remain in the high TLI group after primary chemotherapy are more likely to benefit from subsequent adjuvant systemic therapy.
One hundred and thirty-seven breast cancer patients, 102 receiving adjuvant chemotherapy and 35 receiving palliative chemotherapy for metastatic disease underwent a 37-item quality-of-life questionnaire to evaluate the impact of disease and treatment on physical, psychological and social well being. Patient groups were designated as follows--Adj CT: patients undergoing the questionnaire during their adjuvant chemotherapy program; Post Adj CT: patients evaluated 3 to 8 months after termination of adjuvant chemotherapy; Mts CT: patients assessed during palliative chemotherapy for metastatic disease, and Post Mts CT: patients 3 to 8 months after termination of palliative chemotherapy. Physical and social activities were reported as unaltered or normal by 64 to 70% and 52 to 67% of patients, respectively. Psychological status was judged normal by 39 to 45% of patients. No significant differences were observed between the patients groups. In 83 to 90% of cases the patient normally took care of herself. In 62 to 87% of cases time dedicated to recreational activities was reported as unaltered. The majority of patients (84%) judged that their relationship with partner and/or family were good. Severe anxiety was reported in 19 to 28% of patients and severe depression was infrequent (3.9%). Information regarding disease and treatment given by health professionals was considered satisfactory by 80 to 100% of patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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