NEOLBC

Population (base)

Postmenopausal patients with hormone receptor positive (ER≥50%, PR any), HER2 negative, stage II/III breast cancer, amenable to receive dose dense neoadjuvant AC – T (4x docetaxel 3-weekly or 12x paclitaxel weekly) chemotherapy for early breast cancer.

Inclusion criteria

• In order to be eligible to participate in this study, a subject must meet all of the following criteria: Postmenopausal women presenting with histological proven (core biopsy material) hormone receptor positive (ER≥50%, PR any), HER2 negative, stage II/ III breast
• Measurable disease (breast and/or lymph nodes) WHO 0-2
• Adequate bone marrow function (within 4 weeks prior to registration): WBC≥3.0×109/l, neutrophils ≥1.5 x 109/l, platelets ≥100 x 109/l
• Adequate liver function (within 4 weeks prior to registration): bilirubin ≤1.5 x upper limit of normal (UNL) range, ALAT and/or ASAT ≤2.5 x UNL, Alkaline Phosphatase ≤5 x UNL
• Adequate renal function (within 4 weeks prior to registration): the calculated creatinine clearance should be ≥50 ml/min
• Accessible for treatment and follow-up
• Written informed consent

Inclusion criteria – randomization specific

In order to be eligible to be randomized in this study, a subject must meet all of the following criteria:

• Registration in the NEOLBC trial before 2 weeks biopsy
• Use of letrozole
• Outcome central Ki67 determination in two weeks biopsy

Exclusion criteria

• Evidence of distant metastases (M1)
• Previous invasive breast cancer
• Prior chemotherapy, radiation therapy or hormonal therapy with the exception of patients who received letrozole ≤ 14 days (+ max. 4 days) prior to registration and who are still on letrozole.
• Previous malignancy within 5 years, with exception of a history of a previous basal cell carcinoma of the skin or pre-invasive carcinoma of the cervix.
• Peripheral neuropathy > grade 2, whatever the cause
• Serious other diseases as infections (hepatitis B, C and HIV), recent myocardial infarction, clinical signs of cardiac failure or clinically significant arrhythmias or on screening, any of the following cardiac parameters: bradycardia (heart rate <50 at rest) or QTcF ≥450 msec.
• Known hypersensitivity reaction to any of the components of the treatment (peanuts, soy)
• Currently receiving warfarin or other coumarin derived anti-coagulant, for treatment, prophylaxis or otherwise. Therapy with heparin, low molecular weight heparin (LMWH), or fondaparinux is allowed.
• Currently receiving any of the following substances and cannot be discontinued 7 days prior to randomisation:
• • Known strong inducers or inhibitors of CYP3A4/5, including grapefruit, grapefruit hybrids, pummelos, star-fruit, pomegranate and Seville oranges.
  • That have a known risk to prolong the QT interval or induce Torsades de Pointes.
  • That have a narrow therapeutic window and are predominantly metabolized through CYP3A4/5. Herbal preparations/medications, dietary supplements.
• Medical or psychological condition which in the opinion of the investigator would not permit the patient to complete the study or sign meaningful informed consent.