Project description:Trial 223 was a placebo-controlled trial of neoadjuvant anastrozole alone or with gefitinib in early breast cancer. We used patients from arm B and C: anastrozole 1mg/d for the duration of the 16 week period plus placebo 1 tablet/d orally for 2 weeks. Patients in arm B were followed by gefitinib 250mg/d orally for 14 weeks whereas patients in arm C continued with placebo for 14 weeks. 96 samples
Project description:Trial 223 was a placebo-controlled trial of neoadjuvant anastrozole alone or with gefitinib in early breast cancer. We used patients from arm B and C: anastrozole 1mg/d for the duration of the 16 week period plus placebo 1 tablet/d orally for 2 weeks. Patients in arm B were followed by gefitinib 250mg/d orally for 14 weeks whereas patients in arm C continued with placebo for 14 weeks.
Project description:Transcriptome of 17 tru-cut biopsies and 13 matched surgical samples from ER+ breast tumor patients, treated for 3 months with Anastrozole were anayzed to identify a robust expression signature predictive of response to Anastrozole neoadjuvant treatment in ER+ breast cancer patients and, at the same time, to delineate treatment effects.
Project description:A phase II neoadjuvant trial of anastrozole (A), fulvestrant (F) and gefitinib (I - iressa) in patients with newly diagnosed estrogen receptor positive breast cancer
Project description:Endocrine therapy in patients with breast cancer can be limited by the problem of resistance. Preclinical studies suggest that complete blockade of the estrogen receptor (ER) combined with inhibition of the epidermal growth factor receptor (EGFR) can overcome endocrine resistance. We tested this hypothesis in a phase II neoadjuvant trial of anastrozole and fulvestrant combined with gefitinib in postmenopausal women with newly diagnosed ER-positive breast cancer. After a baseline tumor core biopsy, patients were randomized to receive anastrozole and fulvestrant (AF) or anastrozole, fulvestrant, and gefitinib (AFG) for 3 weeks. After a second biopsy at 3 weeks, all patients received AFG for 4 months and surgery was done if the tumor was operable. The primary endpoint was best clinical response by RECIST criteria and secondary endpoints were toxicity and change in biomarkers. The study closed after 15 patients were enrolled because of slow accrual. Median patient age was 67 years and median clinical tumor size was 7 cm. Four patients had metastatic disease present. Three patients withdrew before response was assessed. In the remaining twelve patients, there were two complete clinical responses (17%), three partial responses (25%), five had stable disease (41%), and two (17%) had progressive disease. Most common adverse events were rash in four patients, diarrhea in four, joint symptoms in three, and abnormal liver function tests in three. There were no grade 4 toxicities and all toxicities were reversible. At 3 weeks, cell proliferation as measured by Ki-67 was significantly reduced in the AFG group (p value= 0.01) with a parallel reduction in the expression of the Cyclin D1 (p value=0.02). RNA microarray data showed a corresponding decrease in the expression of cell cycle genes. These results suggest that AFG was an effective neoadjuvant therapy and consistently reduced proliferation in ER-positive tumors.
Project description:To identify the effect of 16 weeks of neoadjuvant anastrozole treatment on gene expression profiles of oestrogen receptor positive breast tumours from post-menopausal patients.
