Primary operable breast cancer
Conditions
Interventions
Randomization:
To one of the treatment arms (6 cycles TAC or AC dd).
ACdd:
Doxorubicin 60 mg/m2 i.v. bolus and cyclophosphamide 600 mg/m2 i.v. bolus on day 1 every 2 weeks.
TAC:
Doxorubicin 50 mg
2. Radiotherapy, if indicated
3. Endocrine treatment for at least 5 years, (according to the most recent Dutch national guidelines)starting 1 to 6 weeks after radiotherapy or 3 to 6 weeks after chemotherapy for patients with posit
Sponsors
Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital
Eligibility
Inclusion criteria
Inclusion criteria: 1. Women with pT1-T3, pN0-3b, M0 adenocarcinoma of the breast (TNM classification 2002). Women with a macrometastasis in the sentinel node, who did not receive an axillary dissection (pN1(sn)), are only eligible if radiotherapy of the axilla is included in the treatment plan (for instance experimental arm AMAROS study); 2. Known HER2 and estrogen receptor status; 3. Frozen tumor tissue available (or tumor tissue sent in RNAlater to NKI-AVL); 4. Primary surgery (defined as date of last surgical intervention) < 6 weeks before randomisation, or radiotherapy < 5 weeks before randomisation; 5. Good performance status (WHO < 1); 6. Normal hematology, normal renal and liver function tests (see below); 7. No history of heart failure; 8. Patients of childbearing potential must implement adequate non-hormonal contraceptive measures during study treatment (chemotherapy and hormonal therapy); 9. No conditions that may compromise follow-up; 10. Informed consent; 11. At least 18 years old and able to undergo intensive chemotherapy (in the study of Martin et al. employing the TAC regimen (1d) age < 65 years was required); 12. Laboratory requirements: (within 14 days prior to registration): Hematology: Neutrophils ≥ 1.5 109/L; Platelets ≥ 100 109/L; Hemoglobin ≥6.0 mmol/L. Hepatic function: Total bilirubin ≤ 16 umol/L; ASAT (SGOT) and ALAT (SGPT) ≤ 1.5 UNL; Alkaline phosphatase ≤ 2.5 UNL. Renal function: Creatinine ≤ 120 µmol/L; If limit values, the calculated creatinine clearance should be ≥ 60 mL/min.
Exclusion criteria
Exclusion criteria: 1. Prior systemic anticancer therapy for any cancer (immunotherapy, hormonal therapy, chemotherapy); 2. Prior radiation therapy for breast cancer; 3. HER2 positive breast cancer (except for patients who are going to be treated according to HERA study (1c)(see also ‘Dosage regimens’ p 8-9); 4. Pregnant, or lactating patients; 5. Pre-existing motor or sensory neurotoxicity of a severity > grade 2 by NCI criteria; 6. Other serious illness or medical condition: A. Congestive heart failure or unstable angina pectoris, previous history of myocardial infarction within 1 year from study entry, uncontrolled hypertension or high-risk uncontrolled arrhythmias; B. History of significant neurological or psychiatric disorders including psychotic disorders, dementia or seizures that would prohibit the understanding and giving of informed consent; C. Active uncontrolled infection. 7. Past history of invasive breast cancer or past or current history of neoplasm other than breast carcinoma, except for: A. Curatively treated non-melanoma skin cancer; B. In situ carcinoma of the cervix; C. Ipsilateral ductal carcinoma in-situ (DCIS) of the breast; D. Lobular carcinoma in-situ (LCIS) of the breast. 8. Concurrent treatment with other experimental drugs. Participation in another clinical trial with any investigational not marketed drug within 30 days prior to study entry; 9. Male patients.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To define gene expression profiles that can predict a disease-free survival (DFS) advantage for either dose dense therapy, or docetaxel—containing chemotherapy. | — |
Secondary
| Measure | Time frame |
|---|---|
| Is docetaxel-doxorubicin-cyclophosphamide (TAC) better than doxorubicin-cyclophosphamide dose-dense (AC dd) concerning DFS, RFS, breast cancer specific survival and all cause survival? Objectives of optional side studies: 1. To determine whether the proteomic profile of patients, with primary breast cancer, relates to patient demographic characteristics, tumor stage, tumor biologic characteristics or tumor genetic (micro-array) profile; 2. To identify a proteomic pattern that positively or negatively predicts relapse according to the genetic profile of the primary tumor (micro-array analysis) in each treatment arm; 3. To identify a proteomic pattern in follow-up serum samples that can predict for relapse. | — |
Contacts
Public ContactS.C. Linn
Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Departments of Molecular Biology and Medical Oncology, Plesmanlaan 121
Outcome results
None listed