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Impact of chemotherapy on telomere length in sporadic and familial breast cancer patients

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Abstract

Recently, we observed that telomeres of BRCA1/2 mutation carriers were shorter than those of controls or sporadic breast cancer patients, suggesting that mutations in these genes might be responsible for this event. Given the contradictory results reported in the literature, we tested whether other parameters, such as chemotherapy, could be modifying telomere length (TL). We performed a cross-sectional study measuring leukocyte TL of 266 sporadic breasts cancer patients treated with first-line chemotherapy, with a median follow-up of 240 days. Additionally, we performed both cross-sectional and longitudinal studies in a series of 236 familial breast cancer patients that included affected and non-affected BRCA1/2 mutation carriers. We have measured in leukocytes from peripheral blood: the TL, percentage of short telomeres (<3 kb), telomerase activity levels and the annual telomere shortening speed. In sporadic cases we found that chemotherapy exerts a transient telomere shortening effect (around 2 years) that varies depending on the drug combination. In familial cases, only patients receiving treatment were associated with telomere shortening but they recovered normal TL after a period of 2 years. Chemotherapy affects TL and should be considered in the studies that correlate TL with disease susceptibility.

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Acknowledgments

We thank Alicia Barroso and Victoria Fernandez for their technical support. This work was partially funded by project FIS PI12/00070 from the Carlos III Health Institute and the Spanish Network on Rare Diseases (CIBERER) and by project SAF2012-35779 (Spanish Ministry of Economy and Competiveness). M.A.B.’s Laboratory is funded with the Spanish Ministry of Science and Innovation, Projects SAF2008-05384 and 2007-A-200950 (TELOMARKER), European Research Council Advanced Grant GA#232854, the Körber Foundation, Botín Foundation, and Lilly Foundation.

Conflict of interest

The authors declare that they have no conflicts of interest.

Ethical Standards

The authors declare that this work complies with current Spanish laws.

Author information

Authors and Affiliations

  1. Human Genetics Group, Spanish National Cancer Research Center (CNIO), 28029, Madrid, Spain

    C. Benitez-Buelga, K. Yanowski, A. Osorio & J. Benitez

  2. Endocrine Cancer Group, Spanish National Cancer Research Center (CNIO), 28029, Madrid, Spain

    L. Sanchez-Barroso, María Apellániz-Ruiz, L. Inglada-Pérez & C. Rodriguez-Antona

  3. Telomere and Telomerase Group, Spanish National Cancer Research Center (CNIO), 28029, Madrid, Spain

    M. Gallardo & M. A. Blasco

  4. Center for Biomedical Network Research on Rare Diseases (CIBERER), CNIO, 28029, Madrid, Spain

    L. Inglada-Pérez, J. Carrillo, R. Perona, M. Urioste, A. Osorio, C. Rodriguez-Antona & J. Benitez

  5. Biomedical Research Institute Alberto Sols (CSIC-UAM), 28029, Madrid, Spain

    J. Carrillo & R. Perona

  6. Medical Oncology Dptm., Centro Integral Oncológico Clara Campal, Madrid, Spain

    L. Garcia-Estevez

  7. Medical Oncology Dptm., Hospital Montepríncipe, Madrid, Spain

    I. Calvo

  8. Familial Cancer Unit, Spanish National Cancer Research Center (CNIO), 28029, Madrid, Spain

    M. Urioste

Authors
  1. C. Benitez-Buelga
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  2. L. Sanchez-Barroso
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  3. M. Gallardo
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  4. María Apellániz-Ruiz
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  5. L. Inglada-Pérez
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  6. K. Yanowski
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  7. J. Carrillo
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  8. L. Garcia-Estevez
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  9. I. Calvo
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  10. R. Perona
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  11. M. Urioste
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  12. A. Osorio
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  13. M. A. Blasco
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  14. C. Rodriguez-Antona
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  15. J. Benitez
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Corresponding author

Correspondence to J. Benitez.

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Benitez-Buelga, C., Sanchez-Barroso, L., Gallardo, M. et al. Impact of chemotherapy on telomere length in sporadic and familial breast cancer patients. Breast Cancer Res Treat 149, 385–394 (2015). https://doi.org/10.1007/s10549-014-3246-6

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  • DOI: https://doi.org/10.1007/s10549-014-3246-6

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