Phosphatidylinositol 3-kinase pathway activation in breast cancer brain metastases Public Deposited

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Creator
  • Prat, Aleix
    • Affiliation: School of Medicine, Department of Genetics, Department of Pathology and Laboratory Medicine, N.C. Cancer Hospital, UNC Lineberger Comprehensive Cancer Center
  • Carey, Lisa
    • Affiliation: School of Medicine, Division of Hematology/Oncology, N.C. Cancer Hospital, UNC Lineberger Comprehensive Cancer Center, Department of Medicine
  • Livasy, Chad
    • Other Affiliation: Department of Pathology, Carolinas Medical Center, P.O. Box 32187, Charlotte, NC 28232, USA
  • Ewend, Matthew G.
    • Affiliation: N.C. Cancer Hospital, UNC Lineberger Comprehensive Cancer Center, School of Medicine, Department of Neurosurgery
  • Hamilton, Erika
    • Other Affiliation: Department of Medicine, Division of Hematology-Oncology, 382 Hanes Building, Duke University Medical Center, Box 102382, Durham, NC 27710, USA
  • Harrell, J Chuck
    • Affiliation: School of Medicine, Department of Genetics, Department of Pathology and Laboratory Medicine, N.C. Cancer Hospital, UNC Lineberger Comprehensive Cancer Center
  • Miller, C. Ryan
    • Affiliation: School of Medicine, Department of Pathology and Laboratory Medicine, N.C. Cancer Hospital, UNC Lineberger Comprehensive Cancer Center
  • Adamo, Barbara
    • Affiliation: School of Medicine, Division of Hematology/Oncology, N.C. Cancer Hospital, UNC Lineberger Comprehensive Cancer Center, Department of Medicine
    • Other Affiliation: Department of Human Pathology, Integrated Therapies in Oncology Unit, University of Messina, Messina 98125, Italy
  • Geradts, Joseph
    • Other Affiliation: Department of Pathology, Duke University Medical Center, Box 3712, Durham, NC 27710, USA
  • Deal, Allison M
    • Affiliation: N.C. Cancer Hospital, UNC Lineberger Comprehensive Cancer Center, School of Medicine
    • Other Affiliation: Biostatistics and Clinical Data Management Core
  • Anders, Carey
    • Affiliation: School of Medicine, Division of Hematology/Oncology, N.C. Cancer Hospital, UNC Lineberger Comprehensive Cancer Center, Department of Medicine
  • Fritchie, Karen
    • Other Affiliation: Department of Pathology, Mayo Clinic, 13400 East Shea Boulevard, Rochester, MN 85259, USA
  • Burrows, Emily
    • Affiliation: N.C. Cancer Hospital, UNC Lineberger Comprehensive Cancer Center, School of Medicine
  • Blackwell, Kimberly L
    • Other Affiliation: Department of Medicine, Division of Hematology-Oncology, 382 Hanes Building, Duke University Medical Center, Box 102382, Durham, NC 27710, USA
Abstract
  • Abstract Introduction Activation status of the phosphatidylinositol 3-kinase (PI3K) pathway in breast cancer brain metastases (BCBMs) is largely unknown. We examined expression of phospho(p)-AKT, p-S6, and phosphatase and tensin homologue (PTEN) in BCBMs and their implications for overall survival (OS) and survival after BCBMs. Secondary analyses included PI3K pathway activation status and associations with time to distant recurrence (TTDR) and time to BCBMs. Similar analyses were also conducted among the subset of patients with triple-negative BCBMs. Methods p-AKT, p-S6, and PTEN expression was assessed with immunohistochemistry in 52 BCBMs and 12 matched primary BCs. Subtypes were defined as hormone receptor (HR)+/HER2-, HER2+, and triple-negative (TNBC). Survival analyses were performed by using a Cox model, and survival curves were estimated with the Kaplan-Meier method. Results Expression of p-AKT and p-S6 and lack of PTEN (PTEN-) was observed in 75%, 69%, and 25% of BCBMs. Concordance between primary BCs and matched BCBMs was 67% for p-AKT, 58% for p-S6, and 83% for PTEN. PTEN- was more common in TNBC compared with HR+/HER2- and HER2+. Expression of p-AKT, p-S6, and PTEN- was not associated with OS or survival after BCBMs (all, P > 0.06). Interestingly, among all patients, PTEN- correlated with shorter time to distant and brain recurrence. Among patients with TNBC, PTEN- in BCBMs was associated with poorer overall survival. Conclusions The PI3K pathway is active in most BCBMs regardless of subtype. Inhibition of this pathway represents a promising therapeutic strategy for patients with BCBMs, a group of patients with poor prognosis and limited systemic therapeutic options. Although expression of the PI3K pathway did not correlate with OS and survival after BCBM, PTEN- association with time to recurrence and OS (among patients with TNBC) is worthy of further study.
Date of publication
Identifier
  • doi:10.1186/bcr3071
  • 22132754
Resource type
  • Article
Rights statement
  • In Copyright
Rights holder
  • Barbara Adamo et al.; licensee BioMed Central Ltd.
License
Journal title
  • Breast Cancer Research
Journal volume
  • 13
Journal issue
  • 6
Page start
  • R125
Language
  • English
Is the article or chapter peer-reviewed?
  • Yes
ISSN
  • 1465-5411
Bibliographic citation
  • Breast Cancer Research. 2011 Dec 01;13(6):R125
Access
  • Open Access
Publisher
  • BioMed Central Ltd
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