PIK3CA mutations and BRCA1 expression in breast cancer: potential biomarkers for chemoresistance.
Mutations in PIK3CA and alterations of BRCA1 expression are common in breast cancer and have been correlated with altered sensitivity to taxanes in human cancer cell lines and with outcome of patients. We assessed mutations in the three hotspots of PIK3CA (E542K, E545K and H1047R) and intratumoral BRCA1 mRNA expression by quantitative RT-PCR in 61 breast cancer patients. Mutations of PIK3CA were found in 17 (27.9%) and did not correlate with BRCA1 transcript levels. Correlation with clinical and pathological features identified a significant association of mutations with older patients (P = 0.03). Higher BRCA1 mRNA expression was significantly correlated with advanced disease (P = 0.01) and ERBB2 overexpression (P = 0.02). These findings may help to identify a subgroup of patients who will likely benefit from chemotherapy regimens containing microtubule-disrupting agents.
Santarpia
Mariacarmela
M
Human Pathology Department, Medical Oncology Unit, University of Messina, Italy.
Altavilla
Giuseppe
G
Margeli
Mireia
M
Cirauqui
Beatriz
B
Mesiti
Mario
M
Cavallari
Vittorio
V
Ramirez
Jose Luis
JL
Sanchez-Ronco
Maria
M
Santarpia
Libero
L
Taron
Miquel
M
Rosell
Rafael
R
D019313:BRCA1 Protein / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000235:genetics; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D058534:Class I Phosphatidylinositol 3-Kinases; D003062:Codon / Q000235:genetics; D017931:DNA Primers; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D006801:Humans; D009154:Mutation; D009367:Neoplasm Staging; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D016896:Treatment Outcome
D019313:BRCA1 Protein; D014408:Biomarkers, Tumor; D058534:Class I Phosphatidylinositol 3-Kinases; D003062:Codon; D017931:DNA Primers; D019869:Phosphatidylinositol 3-Kinases; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D018719:Erb-b2 Receptor Tyrosine Kinases; C492913:BRCA1 protein, human; C484760:PIK3CA protein, human; C508053:ERBB2 protein, human