PIK3CA E545G

The genomic profiling performed using biopsies from young colorectal cancer patients provides a unique ability to identify the potential “genomic triggers� for the development and progression of cancer in these patients. In this study, in addition to known colorectal cancer associated gene mutations, we identified recurrent missense mutations in DDR2 oncogene. This information can be further used to develop not only targeted treatment options for these patients but also to design new screening protocols for identifying high risk patients for optimal surveillance.

In this group of HR/HER2 breast cancer patients, common PIK3CA gene mutations account for the vast majority of the mutations. New rare variants in PIK3CA are also identified while their clinical significance needs to be further studied in a large cohort and/or multi-center study.

P2, N=11, Completed, NRG Oncology | Active, not recruiting --> Completed

P=N/A, N=200, Recruiting, Novartis Pharmaceuticals | Not yet recruiting --> Recruiting

Background: ALP is an alpha-selective PI3K-inhibitor approved in combination with fulvestrant for PIK3CA -mt HR+/HER2- advanced breast cancer (aBC). Table 1. Frequency of co- occurring alterations by PIK3CA -mt clonality

56 patients received therapy of inhibitors of cycline-dependent kinase CDK4/6 in combination with Letrosol or Fulvestrant.21 patients received therapy of inhibitors of cycline-dependent kinase CDK4/6 as a first line treatment, 19 patients as a second line treatment, 13 patients as a third line treatment and 3 patients as a forth and more line treatment...Median time of remission in patients who received treatment in an adjuvant setting with standard hormonal therapy - Tamoxifen or aromatase inhibitors Anastrazol or Letrozol is 41 months against 50 months in groups of with mutations and without respectively...Age of onset didn’t influence the detection of mutations in PIK3CA gene. Patients with mutation in Exon9 had less PFS compared to patients without any mutations but the difference is not statistically significant.

P, N=200, Not yet recruiting, Novartis Pharmaceuticals

Our study reveals the heterogeneity in PI3K-AKT-mTOR pathway among the breast cancer molecular subtypes in our cohort. Moreover, the number and specific sites of PIK3CA mutations have distinct prognostic impact.

All the patients received therapy of inhibitors of cycline- dependent kinase CDK4/6 in combination with aromatase inhibitors or Fulvestrant; in all cases they have received prior anticancer therapy and showed progression...Conclusion A mutation in the PIK3CA gene as a part of tumor genesis is a response predictor to treatment of metastatic breast cancer. Patients with a mutation in the PIK3CA gene in comparison with a control group presented worse results of progression free survival.

All the patients received therapy of inhibitors of cycline- dependent kinase CDK4/6 in combination with aromatase inhibitors or Fulvestrant; in all cases they have received prior anticancer therapy and showed progression...Conclusion A mutation in the PIK3CA gene as a part of tumor genesis is a response predictor to treatment of metastatic breast cancer. Patients with a mutation in the PIK3CA gene in comparison with a control group presented worse results of progression free survival.

All the patients received therapy of inhibitors of cycline- dependent kinase CDK4/6 in combination with aromatase inhibitors or Fulvestrant; in all cases they have received prior anticancer therapy and showed progression...Conclusion A mutation in the PIK3CA gene as a part of tumor genesis is a response predictor to treatment of metastatic breast cancer. Patients with a mutation in the PIK3CA gene in comparison with a control group presented worse results of progression free survival.

All the patients received therapy of inhibitors of cycline- dependent kinase CDK4/6 in combination with aromatase inhibitors or Fulvestrant; in all cases they have received prior anticancer therapy and showed progression...Conclusion A mutation in the PIK3CA gene as a part of tumor genesis is a response predictor to treatment of metastatic breast cancer. Patients with a mutation in the PIK3CA gene in comparison with a control group presented worse results of progression free survival.

Methods Thirty pts treated with palbociclib (n=26) or ribociclib (n=4) plus hormonal therapy were enrolled. Funding: Has not received any funding. Clinical trial identification: Circus study - ID 5694.

We elucidated that ctDNA mutations on PIK3CA and other genes dramatically increased in Stage IV patients compared to Stage III patients which provides a new insight on the Stage III and Stage IV MBC determination. New set of genes especially PIK3CA are identified to correlate with metastasis and affect the outcome which may also be reliably used to monitor the response to therapy. Research Funding: Lynn Sage Breast Cancer Research OncoSET Program, Robert H Lurie Cancer Center