title: NSAID analgesic ketorolac used perioperatively may suppress early breast cancer relapse: particular relevance to triple negative subgroup.
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.
authors.affiliation: Harvard School of Public Health, BLDG I, Rm 1311, 665 Huntington, Ave, Boston, MA 02115, USA. michael.retsky@gmail.com
authors.forename: Michael
authors.initials: M
authors.lastname: Retsky
authors.forename: Rick
authors.initials: R
authors.lastname: Rogers
authors.forename: Romano
authors.initials: R
authors.lastname: Demicheli
authors.forename: William Jm
authors.initials: WJ
authors.lastname: Hrushesky
authors.forename: Isaac
authors.initials: I
authors.lastname: Gukas
authors.forename: Jayant S
authors.initials: JS
authors.lastname: Vaidya
authors.forename: Michael
authors.initials: M
authors.lastname: Baum
authors.forename: Patrice
authors.initials: P
authors.lastname: Forget
authors.forename: Marc
authors.initials: M
authors.lastname: Dekock
authors.forename: Katharina
authors.initials: K
authors.lastname: Pachmann
mesh_terms: D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000378:metabolism / Q000517:prevention & control* / Q000601:surgery; D003131:Combined Modality Therapy; D003198:Computer Simulation; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D020910:Ketorolac / Q000627:therapeutic use*; D008954:Models, Biological; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control*; D059035:Perioperative Period; D016016:Proportional Hazards Models; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D012189:Retrospective Studies
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D020910:Ketorolac; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C508053:ERBB2 protein, human