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Male BC is usually ER, PR and AR-positive, Luminal B-like/HER2-negative. Of note, 56% patients had T1 tumors but only 4% had BCS. ER was highly positive in >90% of cases but only 77% received adjuvant ET. ER, PR and AR were associated with OS and RFS, whereas grade, Ki67 and IHC surrogates were not. Significant improvement in survival over time was observed.

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Background This study tested the hypothesis that docetaxel confers a greater advantage over anthracyclines in p53 mutant compared to p53 wild type breast cancers. Methods Patients with locally advanced, inflammatory or large operable breast cancers were randomised to receive neoadjuvant chemotherapy consisting of either a standard anthracycline regimen (FEC 100 or tailored FEC) or a taxane-based regimen (docetaxel for 3 cycles, followed by epirubicin and docetaxel for 3 cycles). In this open label study, randomisation was performed using a minimisation method that stratified by institution and initial tumour stage (large operable versus locally advanced or inflammatory breast cancer). p53 status was assessed with a yeast functional assay on tumour biopsies taken before chemotherapy. The primary endpoint was a comparison of progression-free survival in the two arms according to p53 status and in the entire trial population (by intention to treat). We report the final analysis of the trial. The study is registered in ClinicalTrials.gov, number NCT00017095. Findings 1856 patients were enrolled and 370 were unassessable for p53 tumour status (the main reason being low tumour cell content in the biopsy). 675 events for the primary endpoint were registered. The hazard ratio (HR) between the two arms for progression-free survival (PFS) was 0.84 (98% CI: 0.63–1.14; p=0.17) in the p53 mutant group and 0.89 (98% CI: 0.68–1.18; p=0.35) in the p53 wild type group. In the entire population, the HR was 0.85 (98% CI: 0.71–1.02; p=0.035) for the use of docetaxel. The most common grade 3 or 4 adverse events were neutropenia in 1598 patients (86.6%), febrile neutropenia in 284 (15.4%), fatigue in 136 (7.4%), infection in 121 (6.6%) and nausea or vomiting in 89 (4.8%). Two patients died of toxicity during or within 30 days of chemotherapy completion and without disease relapse (one in each arm). Interpretation Although p53 status is prognostic for overall survival, it was not predictive of preferential sensitivity to taxanes. p53 status tested by yeast assay in this population can not be used to select patients for FEC versus taxane-based chemotherapy. Funding National Cancer Institute (USA), “La Ligue Nationale Contre le Cancer”, EU (fp6 Active p53 grant), Pharmacia and Sanofi-Aventis.