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Activation of the mTOR signaling pathway in breast cancer and its correlation with the clinicopathologic variables

  • Preclinical Study
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Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

Aims

Rapamycin and its analogues are currently being tested in clinical trials as novel–targeted anticancer agents. Pre-clinical studies that used breast cancer cell lines have suggested that p-Akt or p-S6K1 expressing tumors, as well as PTEN negative tumors, were sensitive to rapamycin. The aims of this study were to determine the proportion of breast cancer that could be candidates for rapamycin treatment and to elucidate the clinicopathologic characteristics and prognosis of potentially rapamycin-sensitive tumors.

Methods

We evaluated the expressions of PTEN, p-Akt and p-S6K1 by performing immunohistochemistry in 122 breast cancer tissues. We analyzed the association of the expression of these proteins with the cliniopathologic variables and the disease-free survival.

Results

PTEN negative tumors, p-Akt expressing tumors and p-S6K1 expressing tumors constituted 4.1% (5/122), 41.0% (50/122), and 36.1% (44/122) of the total tumors, respectively. The proportion of tumors that met the criteria of rapamycin sensitivity was 54.9% (67/122). We could not find any significant correlation between the expression of these proteins and the other prognostic factors. However, the prognosis of tumors with a p-S6K1 expression was significantly worse than that of the p-S6K1 negative tumors.

Conclusion

Based on the status of the PTEN, p-Akt and p-S6K1 expressions as predictors of rapamycin sensitivity, this study suggested that over 50% of breast cancer patients could be potential candidates for rapamycin treatment. In addition, the p-S6K1 expression may constitute an independent prognostic factor for disease-free survival.

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Authors and Affiliations

  1. Department of Surgery, Korea Cancer Center Hospital, 215-4, Gongneung-dong, Nowon-gu, Seoul, 139-706, Korea

    Woo Chul Noh, Hyun-Ah Kim, Nan Mo Moon & Nam-Sun Paik

  2. Department of Surgery, Kangwon National University, College of Medicine, Chuncheon, Korea

    Yang Hee Kim

  3. Department of Pathology, Korea Cancer Center Hospital, Seoul, Korea

    Min Suk Kim & Jae Soo Koh

Authors
  1. Woo Chul Noh
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  2. Yang Hee Kim
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  3. Min Suk Kim
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  4. Jae Soo Koh
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  5. Hyun-Ah Kim
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  6. Nan Mo Moon
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  7. Nam-Sun Paik
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Correspondence to Woo Chul Noh.

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Noh, W.C., Kim, Y.H., Kim, M.S. et al. Activation of the mTOR signaling pathway in breast cancer and its correlation with the clinicopathologic variables. Breast Cancer Res Treat 110, 477–483 (2008). https://doi.org/10.1007/s10549-007-9746-x

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  • DOI: https://doi.org/10.1007/s10549-007-9746-x

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