NSAID analgesic ketorolac used perioperatively may suppress early breast cancer relapse: particular relevance to triple negative subgroup
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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.
KeywordsEarly relapse Analgesia Ketorolac Inflammation NSAID Triple negative breast cancer Computer simulation
Nonsteroid anti-inflammatory drug
Commission d’Ethique Biomédicale Hospitalo-Facultaire de l’Université catholique de Louvain
Circulating tumor cells
Triple negative breast cancer
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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