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BIBTEX RIS

PI3K pathway activation in breast cancer is associated with the basal‐like phenotype and cancer‐specific mortality

2009; Wiley; Volume: 126; Issue: 5 Linguagem: Inglês

10.1002/ijc.24831

ISSN

1097-0215

Autores

Elena López‐Knowles, Sandra O’Toole, Catriona M. McNeil, Ewan K.A. Millar, Min Qiu, Paul Crea, Roger J. Daly, Elizabeth A. Musgrove, Robert L. Sutherland,

Tópico(s)

Advanced Breast Cancer Therapies

Resumo

Abstract Breast cancer is a common malignancy with current biological therapies tailored to steroid hormone (ER, PR) and HER2 receptor status. Understanding the biological basis of resistance to current targeted therapies and the identification of new potential therapeutic targets is an ongoing challenge. The PI3K pathway is altered in a high proportion of breast cancers and may contribute to therapeutic resistance. We undertook an integrative study of mutational, copy number and expression analyses of key regulators of the PI3K pathway in a cohort of 292 invasive breast cancer patients with known treatment outcomes. The alterations identified in this cohort included PIK3CA mutations (12/168, i.e . 7%), PIK3CA copy number gain (28/209, i.e . 14%), PTEN loss (73/258, i.e . 28%) and AKT activation (62/258, i.e . 24%). Overall at least 1 parameter was altered in 72% (139/193) of primary breast cancers. PI3K pathway activation was significantly associated with ER negative ( p = 0.0008) and PR negative ( p = 0.006) status, high tumor grade ( p = 0.032) and a “basal‐like” phenotype ( p = 0.01), where 92% (25/27) of tumors had an altered pathway. In univariate analysis, PI3K pathway aberrations were associated with death from breast cancer; however, this relationship was not maintained in multivariate analysis. No association was identified between an activated pathway and outcome in tamoxifen‐ or chemotherapy‐treated patients. We concluded that >70% of breast cancers have an alteration in at least 1 component of the PI3K pathway and this might be exploited to therapeutic advantage especially in “basal‐like” cancers.

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