PIK3CA exon 9 mutation + HR positive

Other mutations detected were CTNNB1 D32N, KRAS G12V, and PIK3CA E542K Conclusion Resistance development is unavoidable in EGFR mutant advanced NSCLC on any generation of TKIs. NGS offers an advantage in diagnosing mechanism of resistance for further choice of therapy.

21 (58.6%) patients were on palbociclib and 15 (41.4%) on ribociclib along with endocrine therapy. The incidence and type of PIK3CA mutation is similar to the data reported previously. The presence of de novo PI3K mutation confers a worse clinical outcome in HR-positive / HER2 negative metastatic breast cancer patients despite use of CDK4/6 inhibitors. The presence of de novo PIK3CA mutation should be assessed upfront.

The EGFR, KRAS, and PIK3CA gene exon mutation rates differ and were shown to be correlated with different clinical indicators, which have significance in clinical treatment.

Indeed, for rapid results or low-costs procedures, some targeted methods specifically targeting T790M may be used at relapse and may overlook alterations such as C797S or PIK3CA mutations. Targeted next generation sequencing is therefore a recommended option.

MSTS was more representative than RP. Therefore, MSTS can compensate the RP limitations in ITH detection especially in large tumours.

P=N/A, N=750, Completed, New Mexico Cancer Care Alliance | Recruiting --> Completed

KIT exon 11 mutant patients were more favorable in responding to imatinib than those with exon 9 mutant or wild-type GISTs, and compared to non-KIT exon 11 mutant GISTs (p = 0.041)... Massively parallel sequencing can simultaneously provide the MSI status as well as the somatic mutation profile in a single test. This combined approach may help us to understand the molecular pathogenesis of GIST carcinogenesis and malignant progression.

Primary and secondary acquired resistance is unavoidable in EGFR mutant advanced NSCLC on any generation of TKIs . NGS offers an advantage in diagnosing mechanism of resistance for further choice of therapy.

We found that PIK3CA mutation was an adverse predictive marker for the overall survival of stage IV patients and recurrence of stage III patients, respectively. Further more, we suggested that PIK3CA exon 9 mutations are not negative predictors of cetuximab treatment in KRAS, NRAS, and BRAF wild-type mCRC patients.

PIK3CA mutations can be detected using liquid biopsy even in patients with no PIK3CA mutations in their primary tumors; thus, combination analysis using tissue and liquid biopsies can provide clinically useful information for patients with breast cancer.

 PIK3CA mutations are common in luminal breast cancer. These changes also occur among treatment naive patients. The role of such alterations in the natural history of the disease and its role on primary resistance to endocrine therapy remains to be determined.

Finally, AsH patients with the overexpression of PIK3CA or NFκB had the worst overall survival, signifying a strong impact of arsenic on this pathway and outcome of the patients. Thus, our study showed that the arsenic-associated differential molecular profile of PIK3CA/AKT1/NFkB in BlCa has an important role in the molecular pathogenesis of the disease.

Like conventional fibroadenomas, MED12 exon 2 mutations appear to be restricted to the stromal component of CFAs, supporting the notion that CFAs are stromal neoplasms.

The novel p110α L551Q mutation could have carcinogenic feature similar to previously known helical domain mutations.

Mutations in TP53 and PIK3CA hotspot at exon 9 may be potential negative predictors of ER+HER2+ BC treated with neoadjuvant letrozole and lapatinib, while MLL2 inactivating mutation might confer therapeutic benefit in these patients.

ALP plus FUL demonstrated clinical benefit in pts with PIK3CA mutations detected in plasma ctDNA by NGS, in pts with single alterations, and in pts with alterations in exons 9 and 20. Results were consistent across pt groups, except in those with alterations not detectable by PCR. In conclusion, these data demonstrate a consistent clinical benefit of ALP plus FUL in various groups of pts with PIK3CA alterations detected in ctDNA by NGS.

Our study revealed that PI3K pathway was activated in at least 14.9% in EGFR-TKI resistant patients. EGFR-TKIs plus everolimus showed limited antitumor activity in EGFR mutant NSCLC patients with PI3K pathway aberrations.

PIK3CA mutation showed no prognostic impact in the ShortHER trial. Within the HER2-enriched molecular subtype, patients with PIK3CA mutated tumors showed better DFS vs PIK3CA wild-type that may be partly explained by upregulation of immune-related genes.

As PIK3CA mutations were found to be closely associated with KRAS mutations, their relationship warrants further investigation. Since PIK3CA exon 9 and 20 mutations showed different tendencies with regard to BRAF mutation and MSI status, they may have distinct molecular impacts on CRC.

Generally, the prognosis of epithelial ovarian cancer patients with brain metastases is poor. PIK3CA mutations could be a good prognostic indicator in clear cell carcinomas.

Oncogenic mutations can cause changes that can have a drastic impact on transcription. Rearrangement of chromatin topology is a key mechanism by which the transcriptional program of a cell can be modified. Our experiments reveal key sites of chromatin rearrangement caused by a single oncogenic mutation that may promote a cancer phenotype in our cells.

The ShortHER trial randomized 1254 patients with HER2-positive early breast cancer to 9 weeks or 1 year of adjuvant trastuzumab combined with chemotherapy. Within the HER2-enriched molecular subtype, PIK3CA mutated patients showed better DFS as compared to PIK3CA wild-type patients. These results highlight the need to integrate multiple biomarkers in order to dissect the heterogeneity of HER2-positive breast cancer.Legal entity responsible for the study: University of Padua. Funding: Italian Medicines Agency (AIFA, grant FARMS5KR); Italian Association for Cancer Research (AIRC, grant MFAG-15938).

Thirty-six patients who resistance to imatinib or sunitinib were screened. Panel-based NGS could comprehensively elucidated the landscape of GIST and identified more tumor-specific genetic alterations which can be managed by targeted therapy. But immunotherapy and liquid biopsies remains challenging and needs further investigation from our results. T: tissue, B: Blood, R: resistant, S: sensitive Research Funding: None

P2, N=90, Suspended, UNICANCER | Recruiting --> Suspended

The ShortHER trial randomized 1254 patients with HER2-positive early breast cancer to 9 weeks or 1 year of adjuvant trastuzumab combined with chemotherapy. Within the HER2-enriched molecular subtype, PIK3CA mutated patients showed better DFS as compared to PIK3CA wild-type patients. These results highlight the need to integrate multiple biomarkers in order to dissect the heterogeneity of HER2-positive breast cancer.Legal entity responsible for the study: University of Padua. Funding: Italian Medicines Agency (AIFA, grant FARMS5KR); Italian Association for Cancer Research (AIRC, grant MFAG-15938).

P1/2, N=106, Recruiting, Institut Paoli-Calmettes