Preoperative bevacizumab combined with letrozole and chemotherapy in locally advanced ER- and/or PgR-positive breast cancer: clinical and biological activity

Abstract

The antiangiogenic agent bevacizumab showed synergistic effects when combined with chemotherapy in advanced breast cancer. We presently investigated the activity of bevacizumab in combination with chemotherapy, including capecitabine and vinorelbine, and endocrine therapy, including letrozole ( þ triptorelin in premenopausal women), as primary therapy for patients with ER and/or PgR X10% T2 -T4a-c, N0 -N2, M0 breast cancer. Biological end point included the proliferative activity (Ki67), whereas clinical end points were clinical response rate, pathological complete response (pCR) and tolerability. Circulating endothelial cells (CECs) and their progenitors, as surrogate markers of antiangiogenic activity, were measured at baseline and at surgery.Thirty-six women are evaluable. A clinical response rate of 86% (95% CI, 70 -95) and no pCR were observed; Ki67 was significantly decreased by 71% (interquartile range, À82%, À62%). Toxicity was manageable: two grade 3 hypertension, four grade 3 deep venous thrombosis and no grade 42 proteinuria were observed. Treatment significantly decreased the percentage of viable CECs and prevented the chemotherapy-induced mobilisation of circulating progenitors. Basal circulating progenitors were positively associated with clinical response. In conclusion, bevacizumab is feasible and active in association with primary chemoendocrine therapy for ER-positive tumours in terms of proliferation inhibition, clinical response and antiangiogenic activity.

Safety and Therapeutic Effect of Metronomic Chemotherapy with Cyclophosphamide and Celecoxib in Advanced Breast Cancer Patients

“…Antiangiogenic drugs interfere in many common pathways shared in all neoplastic cells in an unspecific fashion [24].…”

Bevacizumab

“…After the administration of 5 or 10 mg/kg of bevacizumab in locally advanced rectal carcinoma patients, CEC levels were lower on days 3 and 12 than at baseline (p Ͻ .01) [42]. In breast cancer patients, treatment with bevacizumab and combination chemotherapy resulted in a lower total number of CECs (p ϭ .07) and CEPs (p ϭ .02) than at baseline [43].…”

Thymidine kinase 1 expression in atypical ductal hyperplasia significantly differs from usual ductal hyperplasia and ductal carcinoma in situ: A useful tool in tumor therapy management

“…For example, neo-adjuvant pre-operative chemotherapy, in combination with radiotherapy, endocrine and immunological treatments, results in a more effective therapy, reducing the risk of recurrence and improving survival rates and the quality of life (1)(2)(3). However, anti-cancer therapy is not yet highly effective, in particular in patients with later-stage breast cancer disease.…”