Analysis of PIK3CA mutations and activation pathways in triple negative breast cancer

Background
Triple Negative Breast Cancer (TNBC) accounts for 12–24% of all breast carcinomas, and
shows worse prognosis compared to other breast cancer subtypes. Molecular studies demonstrated
that TNBCs are a heterogeneous group of tumors with different clinical and pathologic
features, prognosis, genetic-molecular alterations and treatment responsivity. The
PI3K/AKT is a major pathway involved in the regulation of cell survival and proliferation, and
is the most frequently altered pathway in breast cancer, apparently with different biologic
impact on specific cancer subtypes. The most common genetic abnormality is represented
by PIK3CA gene activating mutations, with an overall frequency of 20–40%. The aims of
our study were to investigate PIK3CA gene mutations on a large series of TNBC, to perform
a wider analysis on genetic alterations involving PI3K/AKT and BRAF/RAS/MAPK pathways
and to correlate the results with clinical-pathologic data.
Materials and Methods
PIK3CA mutation analysis was performed by using cobas1 PIK3CA Mutation Test. EGFR,
AKT1, BRAF, and KRAS genes were analyzed by sequencing. Immunohistochemistry was
carried out to identify PTEN loss and to investigate for PI3K/AKT pathways components.
Results
PIK3CA mutations were detected in 23.7% of TNBC, whereas no mutations were identified
in EGFR, AKT1, BRAF, and KRAS genes. Moreover, we observed PTEN loss in 11.3% of tumors. Deregulation of PI3K/AKT pathways was revealed by consistent activation of pAKT
and p-p44/42 MAPK in all PIK3CA mutated TNBC.
Conclusions
Our data shows that PIK3CA mutations and PI3K/AKT pathway activation are common
events in TNBC. A deeper investigation on specific TNBC genomic abnormalities might be
helpful in order to select patients who would benefit from current targeted therapy
strategies