Doxorubicin and Cyclophosphamide (AC) Followed by Weekly Docetaxel as Neoadjuvant Treatment of Breast Cancer Patients

• Clinical response rate
• Toxicity
• Disease-free survival
• Overall survival
• Molecular markers and correlation with response

• Clinical response rate.
• Toxicity.
• Disease-free survival.
• Overall survival.
• Molecular markers and correlation with response.

Treatment consists of 4 AC cycles followed by 2 weekly docetaxel cycles (12 infusions).

The pathological complete response rate obtained in previous studies is around 12%. The expected pathological complete response rate in this study is 25%. With an alpha error of 0.05 and a beta error of 0.2, and following Simon´s 2 phase test, 19 patients are needed initially. With 2 pathological complete responses, patient recruitment will continue until approximately 61 patients are recruited. Twelve pathological complete responses are needed to confirm the study hypothesis.

Inclusion Criteria:

• Written informed consent.
• Patients with breast cancer stages II and IIIA, with histological diagnoses as per true-cut or open biopsy.
• Negative extension study, including bilateral mammography, thoracic x-ray, computed tomography (CT)-scan or abdominal echography and bone scintigraphy.
• Analysis of hormone receptor status in primary tumour. It is highly recommended to obtain a tumour tissue sample before start of treatment, and after definitive surgery. These samples will be analysed centrally by GEICAM.
• Age >= 18 and <= 70 years old.
• Performance status as per Karnofsky index >= 80.
• Minimum life expectancy of 6 months.
• Electrocardiogram (EKG) 12 weeks before registration to the study. If abnormalities are suspected, cardiac function must be assessed by left ventricular ejection fraction (LVEF).
• Haematology: neutrophils >= 2.0 x10^9/l; platelets >= 100 x10^9/l; hemoglobin >=10 g/dl.
• Hepatic function: total bilirubin <= 1 x upper normal limit (UNL); SGOT and SGPT <= 2.5 x UNL; alkaline phosphatase <= 5 x UNL.
• Renal function: creatinine <= 1.5 x UNL; creatinine clearance >= 60 ml/min.
• Patients able to comply with study requirements.
• Negative pregnancy test.
• Adequate contraceptive method during the study and up to 3 months after definitive surgery.

Exclusion Criteria:

• Previous systemic therapy for breast cancer treatment.
• Previous treatments with anthracyclines or taxanes for any malignancy.
• Previous radiotherapy for breast cancer.
• Bilateral invasive breast cancer.
• Pregnant or lactating women.
• Previous motor or sensorial neurotoxicity grade >=2.
• Other serious pathologies: congestive heart failure or angina pectoris; history of myocardial infarction in the previous year; uncontrolled hypertension (HT) or high risk arrhythmias.
• History of neurological or psychiatric impairment, precluding patients from providing free informed consent.
• Active infection.
• Active peptic ulcer; unstable diabetes mellitus.
• History of previous or current malignancies other than breast cancer, except for basal skin carcinoma, cervical in situ carcinoma, other tumour diagnosed and treated more than 10 years before, ductal carcinoma in situ (DCIS) or lobular carcinoma in situ (LCIS).
• Chronic treatment with corticoids unless the treatment started > 6 months before registration to the study, and low doses are administered.
• Substitutive hormonal therapy. This treatment must be interrupted before inclusion in the study.
• Concomitant treatment with other investigational products or administration in the 30 previous days.
• Males.