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NSAID analgesic ketorolac used perioperatively may suppress early breast cancer relapse: particular relevance to triple negative subgroup

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Abstract

To explain a bimodal relapse hazard among early stage breast cancer patients treated by mastectomy we postulated that relapses within 4 years of surgery resulted from something that happened at about the time of surgery to provoke sudden exits from dormant phases to active growth. Relapses at 10 months appeared to be surgery-induced angiogenesis of dormant avascular micrometastases. Another relapse mode with peak about 30 months corresponded to sudden growth from a single cell. Late relapses were not synchronized to surgery. This hypothesis could explain a wide variety of breast cancer observations. We have been looking for new data that might provide more insight concerning the various relapse modes. Retrospective data reported in June 2010 study of 327 consecutive patients compared various perioperative analgesics and anesthetics in one Belgian hospital and one surgeon. Patients were treated with mastectomy and conventional adjuvant therapy. Follow-up was average 27.3 months with range 13–44 months. Updated hazard as of September 2011 for this series is now presented. NSAID ketorolac, a common analgesic used in surgery, is associated with far superior disease-free survival in the first few years after surgery. The expected prominent early relapse events are all but absent. In the 9–18 month period, there is fivefold reduction in relapses. If this observation holds up to further scrutiny, it could mean that the simple use of this safe and effective anti-inflammatory agent at surgery might eliminate most early relapses. Transient systemic inflammation accompanying surgery could be part of the metastatic tumor seeding process and could have been effectively blocked by perioperative anti-inflammatory agents. In addition, antiangiogenic properties of NSAIDs could also play a role. Triple negative breast cancer may be the ideal group with which to test perioperative ketorolac to prevent early relapses.

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Abbreviations

NSAID:

Nonsteroid anti-inflammatory drug

CEBH:

Commission d’Ethique Biomédicale Hospitalo-Facultaire de l’Université catholique de Louvain

CTC:

Circulating tumor cells

TNBC:

Triple negative breast cancer

IL-6:

Interleukin-6

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Acknowledgments

This study was supported in part by Grant no. 100484 from Susan G. Komen for the Cure. The funding organization played no role in design of study, collection and interpretation of data, decision to publish or writing of paper. Brussels data updated September 2011 shown in Fig. 6 were provided by Sarah Amar and analyzed by Romano Demicheli.

Conflict of interest

Michael Retsky has a patent pending for treatment of early stage cancer and is on the Board of Directors of the Colon Cancer Alliance (www.ccalliance.org). Authors declare no other competing interests.

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Authors and Affiliations

  1. Harvard School of Public Health, BLDG I, Rm 1311, 665 Huntington, Ave, Boston, MA, 02115, USA

    Michael Retsky & Rick Rogers

  2. Scientific Directorate, Fondazione IRCCS Istituto Nazionale Tumori, Via Venezian 1, 20133, Milan, Italy

    Romano Demicheli

  3. Oncology Analytics, Inc, 8751 W. Broward Blvd, Suite 500, Plantation, FL, 33324, USA

    William JM Hrushesky

  4. James Paget University Hospital, Lowestoft Road, Gorleston, Great Yarmouth, Norfolk, NR31 6LA, UIK

    Isaac Gukas

  5. Royal Free and UCL Medical School, Centre for Clinical Science and Technology, University College London, Clerkenwell Building, Archway Campus, Highgate Hill, London, N19 5LW, UK

    Michael Retsky & Michael Baum

  6. Department of Anesthesiology, Universite Catholique de Louvain, St-Luc Hospital, av. Hippocrate 10-1821, 1200, Brussels, Belgium

    Patrice Forget & Marc DeKock

  7. Department of Experimental Hematology and Oncology, Clinic for Internal Medicine II, Friedrich Schiller University, 07747, Jena, Germany

    Katharina Pachmann

  8. Clinical Trials Group of the Division of Surgery and Interventional Science, University College London, Clerkenwell Building, Archway Campus, Highgate Hill, London, N19 5LW, UK

    Jayant S. Vaidya

Authors
  1. Michael Retsky
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  2. Rick Rogers
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  3. Romano Demicheli
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  4. William JM Hrushesky
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  7. Michael Baum
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  8. Patrice Forget
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  9. Marc DeKock
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  10. Katharina Pachmann
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Correspondence to Michael Retsky.

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Retsky, M., Rogers, R., Demicheli, R. et al. NSAID analgesic ketorolac used perioperatively may suppress early breast cancer relapse: particular relevance to triple negative subgroup. Breast Cancer Res Treat 134, 881–888 (2012). https://doi.org/10.1007/s10549-012-2094-5

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  • DOI: https://doi.org/10.1007/s10549-012-2094-5

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