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Promising development from translational or perhaps anti-translational research in breast cancer

Michael Retsky12*, Romano Demicheli3, William JM Hrushesky4, Patrice Forget5, Marc De Kock5, Isaac Gukas6, Rick A Rogers1, Michael Baum7, Katharine Pachmann8 and Jayant S Vaidya9

Author Affiliations

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

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

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

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

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

6 James Paget University Hospital, Lowestoft Road, Gorleston, Great Yarmouth, Norfolk, NR31 6LA, UK

7 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

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

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

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Clinical and Translational Medicine 2012, 1:17  doi:10.1186/2001-1326-1-17

Published: 28 August 2012

Abstract

Background

A great deal of the public’s money has been spent on cancer research but demonstrable benefits to patients have not been proportionate. We are a group of scientists and physicians who several decades ago were confronted with bimodal relapse patterns among early stage breast cancer patients who were treated by mastectomy. Since the bimodal pattern was not explainable with the then well-accepted continuous growth model, we proposed that metastatic disease was mostly inactive before surgery but was driven into growth somehow by surgery. Most relapses in breast cancer would fall into the surgery-induced growth category thus it was highly important to understand the ramifications of this process and how it may be curtailed. With this hypothesis, we have been able to explain a wide variety of clinical observations including why mammography is less effective for women age 40–49 than it is for women age 50–59, why adjuvant chemotherapy is most effective for premenopausal women with positive lymph nodes, and why there is a racial disparity in outcome.

Methods

We have been diligently looking for new clinical or laboratory information that could provide a connection or correlation between the bimodal relapse pattern and some clinical factor or interventional action and perhaps lead us towards methods to prevent surgery-initiated tumor activity.

Results

A recent development occurred when a retrospective study appeared in an anesthesiology journal that suggested the perioperative NSAID analgesic ketorolac seems to reduce early relapses following mastectomy. Collaborating with these anesthesiologists to understand this effect, we independently re-examined and updated their data and, in search of a mechanism, focused in on the transient systemic inflammation that follows surgery to remove a primary tumor. We have arrived at several possible explanations ranging from mechanical to biological that suggest the relapses avoided in the early years do not show up later.

Conclusions

We present the possibility that a nontoxic and low cost intervention could prevent early relapses. It may be that preventing systemic inflammation post surgery will prevent early relapses. This could be controlled by the surgical anesthesiologist’s choice of analgesic drugs. This development needs to be confirmed in a randomized controlled clinical trial and we have identified triple negative breast cancer as the ideal subset with which to test this. If successful, this would be relatively easy to implement in developing as well as developed countries and would be an important translational result.

Keywords:
Breast cancer; Early relapses; NSAID; Perioperative ketorolac; Inflammatory oncotaxis; Angiogenesis; Dormancy; Transient systemic inflammation