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PI3K/Akt/mTOR signalling pathway activation in patients with ER‑positive, metachronous, contralateral breast cancer treated with hormone therapy

  • Authors:
    • Hirofumi Kanaizumi
    • Chihiro Higashi
    • Yumiko Tanaka
    • Mika Hamada
    • Wataru Shinzaki
    • Tatsuya Azumi
    • Yukihiko Hashimoto
    • Hiroki Inui
    • Toshiya Houjou
    • Yoshifumi Komoike

  • View Affiliations

  • Published online on: November 26, 2018     https://doi.org/10.3892/ol.2018.9759
  • Pages: 1962-1968
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Abstract

Oestrogen receptor (ER)‑positive, metachronous, contralateral breast cancer (MCBC) sometimes develops during or soon after completion of hormone therapy (HT), but it is uncertain whether it is HT‑resistant. We examined the association between ER‑positive second cancer and activation of the phosphoinositide 3‑kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) and mitogen‑activated protein kinase (MAPK) pathways, which are associated with HT resistance. We examined the treatment‑free interval (time after completion of HT for initial cancer) in 41 patients with ER‑positive MCBC with a history of adjuvant HT for initial cancer (HT group), and initial‑to‑second period duration (time after operation of initial cancer to onset of second cancer) in 17 patients with ER‑positive MCBC in whom adjuvant HT was not applied to the initial tumour (control group or no HT group). Phosphorylated S6 (pS6) and phosphorylated MAPK (pMAPK) were used as indicators of PI3K/Akt/mTOR and MAPK pathway activity, respectively. Tumours were classified as showing negative, positive or strongly positive staining, and the correlation between staining and treatment‑free interval or initial‑to‑second period duration was evaluated using the Spearman's rank correlation coefficient (ρ). Treatment‑free interval and pS6 staining showed a negative correlation (ρ=‑0.5355; P=0.0003) in the HT group. There was no correlation between initial‑to‑second period duration and pS6 staining in the no HT group (ρ=‑0.0814; P=0.756). There was no correlation between pMAPK signalling and the treatment‑free interval in the HT group (ρ=‑0.1560; P=0.330) or the initial‑to‑second period duration in the no HT group (ρ=‑0.0116; P=0.965). Development of a second ER‑positive cancer during or soon after completion of HT for the initial cancer may be associated with activation of the PI3K/Akt/mTOR pathway. Care should be taken during follow‑up and when selecting adjuvant therapy for second cancer.
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February-2019
Volume 17 Issue 2

Print ISSN: 1792-1074
Online ISSN:1792-1082

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  • CiteScore: 6.3
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  • Source Normalized Impact per Paper (SNIP): 0.725
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Spandidos Publications style
Kanaizumi H, Higashi C, Tanaka Y, Hamada M, Shinzaki W, Azumi T, Hashimoto Y, Inui H, Houjou T, Komoike Y, Komoike Y, et al: PI3K/Akt/mTOR signalling pathway activation in patients with ER‑positive, metachronous, contralateral breast cancer treated with hormone therapy. Oncol Lett 17: 1962-1968, 2019
APA
Kanaizumi, H., Higashi, C., Tanaka, Y., Hamada, M., Shinzaki, W., Azumi, T. ... Komoike, Y. (2019). PI3K/Akt/mTOR signalling pathway activation in patients with ER‑positive, metachronous, contralateral breast cancer treated with hormone therapy. Oncology Letters, 17, 1962-1968. https://doi.org/10.3892/ol.2018.9759
MLA
Kanaizumi, H., Higashi, C., Tanaka, Y., Hamada, M., Shinzaki, W., Azumi, T., Hashimoto, Y., Inui, H., Houjou, T., Komoike, Y."PI3K/Akt/mTOR signalling pathway activation in patients with ER‑positive, metachronous, contralateral breast cancer treated with hormone therapy". Oncology Letters 17.2 (2019): 1962-1968.
Chicago
Kanaizumi, H., Higashi, C., Tanaka, Y., Hamada, M., Shinzaki, W., Azumi, T., Hashimoto, Y., Inui, H., Houjou, T., Komoike, Y."PI3K/Akt/mTOR signalling pathway activation in patients with ER‑positive, metachronous, contralateral breast cancer treated with hormone therapy". Oncology Letters 17, no. 2 (2019): 1962-1968. https://doi.org/10.3892/ol.2018.9759