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Phosphatidylinositol 3-kinase pathway activation in breast cancer brain metastases.

Publication ,  Journal Article
Adamo, B; Deal, AM; Burrows, E; Geradts, J; Hamilton, E; Blackwell, KL; Livasy, C; Fritchie, K; Prat, A; Harrell, JC; Ewend, MG; Carey, LA ...
Published in: Breast Cancer Res
2011

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.

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Published In

Breast Cancer Res

DOI

EISSN

1465-542X

Publication Date

2011

Volume

13

Issue

6

Start / End Page

R125

Location

England

Related Subject Headings

  • Survival Analysis
  • Signal Transduction
  • Ribosomal Protein S6 Kinases
  • Proto-Oncogene Proteins c-akt
  • Prognosis
  • Phosphatidylinositol 3-Kinases
  • PTEN Phosphohydrolase
  • Oncology & Carcinogenesis
  • Middle Aged
  • Humans
 

Citation

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Adamo, B., Deal, A. M., Burrows, E., Geradts, J., Hamilton, E., Blackwell, K. L., … Anders, C. K. (2011). Phosphatidylinositol 3-kinase pathway activation in breast cancer brain metastases. Breast Cancer Res, 13(6), R125. https://doi.org/10.1186/bcr3071
Adamo, Barbara, Allison M. Deal, Emily Burrows, Joseph Geradts, Erika Hamilton, Kimberly L. Blackwell, Chad Livasy, et al. “Phosphatidylinositol 3-kinase pathway activation in breast cancer brain metastases.Breast Cancer Res 13, no. 6 (2011): R125. https://doi.org/10.1186/bcr3071.
Adamo B, Deal AM, Burrows E, Geradts J, Hamilton E, Blackwell KL, et al. Phosphatidylinositol 3-kinase pathway activation in breast cancer brain metastases. Breast Cancer Res. 2011;13(6):R125.
Adamo, Barbara, et al. “Phosphatidylinositol 3-kinase pathway activation in breast cancer brain metastases.Breast Cancer Res, vol. 13, no. 6, 2011, p. R125. Pubmed, doi:10.1186/bcr3071.
Adamo B, Deal AM, Burrows E, Geradts J, Hamilton E, Blackwell KL, Livasy C, Fritchie K, Prat A, Harrell JC, Ewend MG, Carey LA, Miller CR, Anders CK. Phosphatidylinositol 3-kinase pathway activation in breast cancer brain metastases. Breast Cancer Res. 2011;13(6):R125.

Published In

Breast Cancer Res

DOI

EISSN

1465-542X

Publication Date

2011

Volume

13

Issue

6

Start / End Page

R125

Location

England

Related Subject Headings

  • Survival Analysis
  • Signal Transduction
  • Ribosomal Protein S6 Kinases
  • Proto-Oncogene Proteins c-akt
  • Prognosis
  • Phosphatidylinositol 3-Kinases
  • PTEN Phosphohydrolase
  • Oncology & Carcinogenesis
  • Middle Aged
  • Humans