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PIK3CA Mutation Associates with Improved Outcome in Breast Cancer
Ist Teil von
Clinical cancer research, 2009-08, Vol.15 (16), p.5049-5059
Ort / Verlag
Philadelphia, PA: American Association for Cancer Research
Erscheinungsjahr
2009
Link zum Volltext
Quelle
EZB Electronic Journals Library
Beschreibungen/Notizen
Purpose: In breast cancer, somatic mutations in the PIK3CA gene are common. The prognostic implication of these activating mutations remains uncertain as moderately sized studies have
yielded variable outcomes. Our aim was to determine the prognostic implications of PIK3CA mutations in breast cancer.
Experimental Design: Archival formalin-fixed paraffin-embedded primary breast tumors, from 590 patients selected for known vital status with a
median follow-up of 12.8 years and a tumor >1 cm, were genotyped for PIK3CA mutations. Mutation rates and associations between
mutation site and clinicopathologic characteristics were assessed. Progression-free survival, overall survival, and breast
cancer–specific survival were examined using Kaplan-Meier or competing risk methodology.
Results: PIK3CA mutation is identified in 32.5% of breast cancers. PIK3CA mutation significantly associates with older age at diagnosis,
hormone receptor positivity, HER2 negativity, lower tumor grade and stage, and lymph node negativity. Patients with PIK3CA
mutated tumors have significant improvement in overall survival ( P = 0.03) and breast cancer–specific survival ( P = 0.004). Analysis for PIK3CA mutation site-specific associations reveals that the H1047R kinase domain mutation highly associates
with node negativity ( P = 0.007), whereas helical domain hotspot mutations associate with older age at diagnosis ( P = 0.004).
Conclusion: This study defines the positive prognostic significance of PIK3CA mutations. This work is clinically relevant, as it will
significantly affect the design of clinical trials planned for phosphatidylinositol 3-kinase–targeted therapy. Future work
may define a population of older age breast cancer patients in whom therapy can be minimized. (Clin Cancer Res 2009;15(16):5049–59)