The enhanced use of currently available therapeutic agents and the development of novel drugs may be facilitated by the novel classification of ovarian cancer based on <i>TP53</i> mutations, the efficacy of poly (ADP-ribose) polymerase inhibitors for tumors with breast cancer 1/2 mutations and the effect of phosphoinositide-3-kinase (PI3K)/mammalian target of rapamycin inhibitors for tumors with mutations in the PI3K/protein kinase B signaling pathway.
The Sequenom MassARRAY System was used to determine the presence of 20 somatic mutations across the PIK3CA gene in 85 oestrogen receptor-positive (ER+) BC patients treated with 2 weeks of anastrozole before surgery.
Resistance to trastuzumab (which is a standard therapy for breast cancer patients with HER2 overexpression) is associated with higher risk of progression or cancer death, and might be related to activation of signalling cascades (PI3K/AKT/mTOR, Ras/Raf/MAPK) and decreased level of their inhibitors.
Exon 20 PIK3CA mutations are relatively frequent in Her-2+ tumors and shorten survival, whereas neither exons 9 and 20 mutations seem related with "triple negative" breast carcinomas.
In a median follow up of 54.4 months, the presence of PIK3CA mutations of cfDNA had significant impacts on relapse-free survival (RFS; P = 0.0072) and breast cancer-specific survival (BCSS; P = 0.016), according to the log-lank test.
Some of the PIK3CA mutations were detected in the early lesions of breast cancer carcinoma, hepatocellular carcinoma, and gastric carcinomas, suggesting that PIK3CA mutation may occur independent of stage of the tumors.
Solid papillary breast carcinomas resembling the tall cell variant of papillary thyroid neoplasms (solid papillary carcinomas with reverse polarity) harbour recurrent mutations affecting IDH2 and PIK3CA: a validation cohort.
This study showed that neuroendocrine breast carcinoma is a distinct subtype of luminal carcinoma with a low rate of PIK3CA mutations and with an aggressive clinical behavior.
Collectively, these findings advance our understanding of PI3K impactful mutations in breast cancer and have important implications for PI3K-targeted therapy in precision oncology.
This study suggests that the Akt inhibitor GDC-0068 may be an encouraging targeted treatment strategy for breast cancer brain metastasis patients with activating mutations in the PI3K pathway.
PIK3CA mutations were more frequent in low-risk luminal BCs (e.g., grade 1 nodev 3, node-negative v -positive), confounding the relationship between mutations and outcome.
PIK3CA mutation status does not change in the majority of patients with breast cancer and the acquisition of mutations in PIK3CA is not responsible for the development of endocrine resistance.
We further validated the approach in breast cancer cells with mutational activation of PIK3CA, where tandem mass spectrometry detected and quantitatively measured the abundance of a helical domain mutant (E545K) of PIK3CA connected to PI3K activation.
The patient underwent successful resection of both her breast and lung cancers, and using standard Sanger sequencing the breast cancer was shown to harbor the identical PIK3CA mutation identified in peripheral blood.