11022 Background: The tumor suppressor gene p53 plays a key role in multiple cellular pathways controlling proliferation, survival, and genomic integrity. Disruption of its function promotes checkpoint defects, genomic instability and inappropriate survival leading to uncontrolled proliferation of damaged cells. The relationship of p53 mutation status to the outcome of patients suggests that p53 mutation status is a potential prognostic and predictive indicator of survival. Immunohistochemical analysis cannot accurately identify p53 mutation status and cannot differentiate between the several functional defects that arise from mutations at specific sites of this multifunctional gene. Methods: The primary objective is to define the rate of pCR in the affected breast after neoadjuvant C+D±T for HER2- or HER2+ BC pts, respectively. Eligibility: infiltrating HER2- or HER2+ stage II/III BC with no evidence of metastases and no prior systemic or local primary treatment. Four 3-week cycles consisted of C 825 mg/m2 bid on days 1–14 and D 75 mg/m2 on day 1. HER2+ pts also received T 4 mg/kg x1 on day -1 followed by 2 mg/kg weekly. Enrollment of 99 HER2- patients is planned. The AmpliChip p53 test (Roche Diagnostics, in development), a DNA microarray-based sequencing method, was used to analyze the p53 mutation status. The AmpliChip p53 test is designed to detect all substitution single base changes and single base deletion in all coding regions of the p53 gene. The genomic DNA was extracted from a biopsy sample from each patient and 50–100 ng genomic DNA was used. Results: A total of 47 p53 mutations were found in 44 of 88 (50%) patients, including 32 missense, 6 frameshift, 8 non-sense, and 1 splice site mutation, and were widely distributed in exon 2, 4, 5, 6, 7, 8, 9 and 10. The p53 mutation status including the type and location will be analyzed in relation to clinical and pathological response. Updated data will be presented. Conclusions: The AmpliChip p53 test is a rapid, accurate, and standardized way to detect p53 mutations. These findings suggest that p53 mutations occur in at least 50% of recently diagnosed BC. No significant financial relationships to disclose.
Molecular basis of RhD-positive/D-negative chimerism in two patients