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Everolimus induced mood changes in breast cancer patients: a case-control study

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Introduction The PI3K/Akt/mTOR pathway plays a critical role in cancer cell growth, proliferation and angiogenesis, but also in brain homeostasis and the pathophysiology of mood disorders. The impact of the mTOR inhibitor everolimus on the mood of breast cancer patients is unknown. Materials and methods Consecutive, post-menopausal metastatic breast cancer patients receiving hormone therapy +/− everolimus were prospectively followed-up using the Beck Depression Inventory (BDI) and the MADRS (Montgomery and Asberg Depression Rating Scale) questionnaires. Results Post hoc tests comparing everolimus + hormonotherapy to hormonotherapy alone demonstrated a significant effect of everolimus after 6 weeks of treatment on BDI scores (t(1,38) = −2.0716, p < 0.05), and after 3 weeks (t(1,38) = −3.9165, p < 0.001) and 6 weeks of treatment (t(1,38) = −2.0373, p < 0.05) on MADRS scores. Analysis within each treatment group showed that the effect of time since treatment initiation on BDI and MADRS scores was specifically observed in the everolimus + hormonotherapy group (F(2,34) = 11.875, p < 0.001 and F(2,34) = 7.820, p < 0.01 respectively), but not in the hormonotherapy alone group (F(2,34) = 1.671, p > 0.2 and F(2,34) = 0.830, p > 0.2 respectively). Conclusions The mTOR inhibitor everolimus induces significant mood alterations in breast cancer patients. The evaluation of psychiatric symptoms is not only mandatory in the context of phase 1, dose-finding studies of PI3K/Akt/mTOR inhibitors, but is also clinically relevant in daily practice.

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Acknowledgements

the authors wish to thank Ms. Helene Shriver for writing assistance.

Author information

Authors and Affiliations

  1. Gustave Roussy Cancer Campus, Department of Cancer Medicine, 114, rue Edouard Vaillant, 94800, Villejuif, France

    Olivier Mir

  2. Paris Descartes University, Sorbonne Paris Cité, Paris, France

    Alexandre Salvador, Cédric Lemogne & Raphaël Gaillard

  3. Department of Psychiatry, Sainte-Anne Teaching Hospital, Paris, France

    Alexandre Salvador & Raphaël Gaillard

  4. Laboratory “Pathophysiology of psychiatric diseases”, Centre of Psychiatry and Neurosciences U894, INSERM, Paris, France

    Alexandre Salvador & Raphaël Gaillard

  5. Gustave Roussy Cancer Campus, Department of Supportive Care and Psycho-Oncology, Villejuif, France

    Sarah Dauchy

  6. Laboratory « Ethics, Science, Health and Society” (ES3), EA 1610, University of Paris Sud, Orsay, France

    Sarah Dauchy

  7. Department of Medical Oncology, Antony Private Hospital, Antony, France

    Stanislas Ropert

  8. AP-HP, Hôpitaux Universitaires Paris Ouest, Service de Psychiatrie de l’adulte et du sujet âgé, Paris, France

    Cédric Lemogne

  9. Laboratory “Vulnerability for psychiatric and addictive disorders”, Centre of Psychiatry and Neurosciences U894, INSERM, Paris, France

    Cédric Lemogne

Authors
  1. Olivier Mir
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  2. Alexandre Salvador
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Correspondence to Olivier Mir.

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Conflict of interest

Dr. Mir has acted as consultant for Amgen, Astra-Zeneca, Bayer, Bristol-Myers Squibb, Eli-Lilly, Novartis, Pfizer, Roche, and Servier.

Dr. Salvador has served as speaker for Servier.

Dr. Dauchy has no conflict of interest to declare.

Dr. Ropert has no conflict of interest to declare.

Prof. Lemogne has acted as consultant for Astra Zeneca, Daiichi-Sankyo, Lundbeck and Servier.

Prof. Gaillard has acted as consultant for Astra Zeneca, Bristol-Myers Squibb, Janssen, Lundbeck, Otsuka, Roche, Sanofi, Servier and Takeda.

Ethical approval

All procedures performed in the present study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study.

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Mir, O., Salvador, A., Dauchy, S. et al. Everolimus induced mood changes in breast cancer patients: a case-control study. Invest New Drugs 36, 503–508 (2018). https://doi.org/10.1007/s10637-017-0554-9

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  • DOI: https://doi.org/10.1007/s10637-017-0554-9

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