Prevalence of Phosphatidylinositol-3-Kinase (PI3K) Pathway Alterations and Co-alteration of Other Molecular Markers in Breast Cancer.

Autor:	Khoury K; Lombardi Comprehensive Cancer Center, MedStar Georgetown University Hospital, Washington, DC, United States., Tan AR; Levine Cancer Institute, Charlotte, NC, United States., Elliott A; Caris Life Sciences, Phoenix, AZ, United States., Xiu J; Caris Life Sciences, Phoenix, AZ, United States., Gatalica Z; Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States., Heeke AL; Levine Cancer Institute, Charlotte, NC, United States.; Caris Life Sciences, Phoenix, AZ, United States., Isaacs C; Lombardi Comprehensive Cancer Center, MedStar Georgetown University Hospital, Washington, DC, United States., Pohlmann PR; Lombardi Comprehensive Cancer Center, MedStar Georgetown University Hospital, Washington, DC, United States., Schwartzberg LS; West Cancer Center, Memphis, TN, United States., Simon M; Karmanos Cancer Institute, Wayne State University, Detroit, MI, United States., Korn WM; Caris Life Sciences, Phoenix, AZ, United States., Swain SM; Lombardi Comprehensive Cancer Center, MedStar Georgetown University Hospital, Washington, DC, United States., Lynce F; Lombardi Comprehensive Cancer Center, MedStar Georgetown University Hospital, Washington, DC, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in oncology [Front Oncol] 2020 Aug 31; Vol. 10, pp. 1475. Date of Electronic Publication: 2020 Aug 31 (Print Publication: 2020).
DOI:	10.3389/fonc.2020.01475
Abstrakt:	Background: PI3K/AKT signaling pathway is activated in breast cancer and associated with cell survival. We explored the prevalence of PI3K pathway alterations and co-expression with other markers in breast cancer subtypes. Methods: Samples of non-matched primary and metastatic breast cancer submitted to a CLIA-certified genomics laboratory were molecularly profiled to identify pathogenic or presumed pathogenic mutations in the PIK3CA-AKT1-PTEN pathway using next generation sequencing. Cases with loss of PTEN by IHC were also included. The frequency of co-alterations was examined, including DNA damage response pathways and markers of response to immuno-oncology agents. Results: Of 4,895 tumors profiled, 3,558 (72.7%) had at least one alteration in the PIK3CA-AKT1-PTEN pathway: 1,472 (30.1%) harbored a PIK3CA mutation, 174 (3.6%) an AKT1 mutation, 2,682 (54.8%) had PTEN alterations ( PTEN mutation in 7.0% and/or PTEN loss by IHC in 51.4% of cases), 81 (1.7%) harbored a PIK3R1 mutation, and 4 (0.08%) a PIK3R2 mutation. Most of the cohort consisted of metastatic sites ( n = 2974, 60.8%), with PIK3CA mutation frequency increased in metastatic (32.1%) compared to primary sites (26.9%), p < 0.001. Other PIK3CA mutations were identified in 388 (7.9%) specimens, classified as "off-label," as they were not included in the FDA-approved companion test for PIK3CA mutations. Notable co-alterations included increased PD-L1 expression and high tumor mutational burden in PIK3CA-AKT1-PTEN mutated cohorts. Novel concurrent mutations were identified including CDH1 mutations. Conclusions: Findings from this cohort support further exploration of the clinical benefit of PI3K inhibitors for "off-label" PIK3CA mutations and combination strategies with potential clinical benefit for patients with breast cancer. (Copyright © 2020 Khoury, Tan, Elliott, Xiu, Gatalica, Heeke, Isaacs, Pohlmann, Schwartzberg, Simon, Korn, Swain and Lynce.)
Databáze:	MEDLINE
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