We sequenced cfDNA of a hormone receptor-positive, HER2-negative metastatic breast cancer (MBC) cohort with a high coverage to examine the prevalence and relevance of any detected variant. cfDNA of 44 MBC patients was isolated, followed by library construction using a customized targeted DNA panel with integrated unique molecular indices analyzing AKT1, AR, BRCA1, BRCA2, EGFR, ERCC4, ERBB2, ERBB3, ESR1, FGFR1, KRAS, MUC16, PIK3CA, PIK3R1, PTEN, PTGFR, and TGFB1.
Except for the overall unfavorable prognostic effect of PIK3CA mutations in trastuzumab-treated MBC, our exploratory findings indicate that the outcome of patients with R-MBC is related to patient benefit from the preceding adjuvant chemotherapy and provide initial evidence that tumor mutational burden may be related to prognosis in dn-MBC, which is of potential clinical relevance and merits further investigation.
Correction to: Unexpected Benefit from Alpelisib and Fulvestrant in a Woman with Highly Pre-treated ER-Positive, HER2-Negative PIK3CA Mutant Metastatic Breast Cancer.
Collectively, these findings suggest that while <i>FGFR1</i> amplification confers broad resistance to ER, PI3K, and CDK4/6 inhibitors, mTOR inhibitors might have a unique therapeutic role in the treatment of patients with ER<sup>+</sup>/FGFR1<sup>+</sup> MBC.
Unexpected Benefit from Alpelisib and Fulvestrant in a Woman with Highly Pre-treated ER-Positive, HER2-Negative PIK3CA Mutant Metastatic Breast Cancer.
Here we show the higher frequency of ESR1 and PIK3CA mutations in the plasma than in the serum in 33 MBC patients; therefore, serum samples should not be considered the preferred source of cfDNA.
Our data suggest that additional PI3K blockade might be effective in enhancing the therapeutic effect of tamoxifen in ER-positive BC and support the rationale combination in clinical trials.
Identification of single nucleotide polymorphisms of the PI3K-AKT-mTOR pathway as a risk factor of central nervous system metastasis in metastatic breast cancer.
A Novel Workflow to Enrich and Isolate Patient-Matched EpCAM<sup>high</sup> and EpCAM<sup>low/negative</sup> CTCs Enables the Comparative Characterization of the PIK3CA Status in Metastatic Breast Cancer.
One patient achieved a complete response (CR; endometrial carcinoma exhibiting both PIK3CA and PTEN mutations and complete PTEN loss) and two had a partial response (PR; both metastatic breast cancer).
Pictilisib PI3Kinase inhibitor (a phosphatidylinositol 3-kinase [PI3K] inhibitor) plus paclitaxel for the treatment of hormone receptor-positive, HER2-negative, locally recurrent, or metastatic breast cancer: interim analysis of the multicentre, placebo-controlled, phase II randomised PEGGY study.
MYC gene copies, centromere status and PI3K activation may adversely impact trastuzumab treated mBC patient outcome and seem worthy validating in larger series.
Six MBC patients with TP53 and/or PIK3CA mutations in pDNA had a significantly worse survival rate (P < .05) after recurrence than that of the other 8 MBC patients without these mutations.
Identification of E545k mutation in plasma from a PIK3CA wild-type metastatic breast cancer patient by array-based digital polymerase chain reaction: Circulating-free DNA a powerful tool for biomarker testing in advance disease.
Phase I/II dose-escalation study of PI3K inhibitors pilaralisib or voxtalisib in combination with letrozole in patients with hormone-receptor-positive and HER2-negative metastatic breast cancer refractory to a non-steroidal aromatase inhibitor.
Here, resistance to a class I PI3K inhibitor in a model of metastatic breast cancer driven by PI3K and MYC was associated with feedback activation of tyrosine kinase receptors (RTKs), AKT, mTOR, and MYC.