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Department
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Vascular Biology
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Hospital Title
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Research Associate
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Academic Title
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Lecturer on Surgery, Harvard Medical School
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Phone
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203-675-0017
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Fax
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Email
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Michael Retsky
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Location
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300 Longwood Avenue
Boston MA 02115
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Michael Retsky is well known for his dogma-challenging theories in breast cancer. In collaboration with Romano Demicheli, MD, PhD, of Milan National Cancer Institute, he proposed in 1997 that in order to fit relapse data, breast cancer growth includes periods of temporary dormancy. Furthermore, he proposed that surgical removal of a primary tumor kick-starts growth of dormant distant single cells and avascular micrometastases. These are large effects in that over half of all breast cancer relapses are accelerated by at least one of these mechanisms. In additional collaboration since 2000 with William Hrushesky, MD, now at University of South Carolina, the earliest relapses (i.e., within 10 months of surgery for patients untreated with adjuvant chemotherapy) were found to occur in 20% of premenopausal node-positive patients.
This effect is analogous to the well-known Lewis lung data reported by Michael O'Reilly while at the Folkman lab (Cell 1994). O'Reilly's experiment was very influential in the formulation of the Retsky et. al. theories.
Retsky, Demicheli and Hrushesky reported in 2001 that surgery-induced angiogenesis quantitatively explains the mammography paradox for women age 40-49. When mammography was first tested in randomized controlled clinical trials, women age 50-59 showed an early-appearing 20-30% mortality benefit. However, when this was evaluated in women age 40-49, there was a counterintuitive early disadvantage that turned into the expected advantage after 6-8 years. Most of the patients in these early trials were not treated with adjuvant therapy. The Retsky et. al. 2001 paper quantitatively showed how surgery induced angiogenesis based on the Milan data agrees with the timing and magnitude of the mammography data. The most recent trial of mammography for women age 40-49 showed a non-significant advantage at 10 years into the trial (Moss, Lancet 2006) whereas there is significant advantage for women age 50-59. Women are now screened starting at age 40 in the US, while in most of Europe it starts at age 50.
Retsky et. al. further proposed in 2004 that surgery-induced angiogenesis explains why adjuvant chemotherapy works best by far for premenopausal-node-positive patients. NIH Consensus reports in 1980 and 1985 suggest adjuvant chemotherapy is useful for premenopausal patients with positive nodes. According to the Retsky et al theory, sudden induced tumor growth after surgery results in a chemosensitive period just at the time when adjuvant chemotherapy was empirically found to be most effective. Two papers from 2004 on this subject (1, 2) have been downloaded over 19,000 times. Coauthors in one of these papers are Dr. Folkman and Dr. Gianni Bonadonna -- who in the 1970s was the first person to use multiple drugs in breast cancer chemotherapy. His CMF protocol was a mainstay in breast cancer therapy and is still widely used.
A paper with surgeon Michael Baum reported that it was known 2000 years ago by premodern "chirurgeons" that surgery to remove a tumor can speed relapses. (See Baum et. al., Brit J Med 2006.) Dr. Baum is a well known cancer researcher and is being awarded the St. Gallen award in March 2007. In Europe, this is considered a very high honor.
Retsky's most recent work includes Nigerian surgeon Isaac Gukas, MD, PhD, as another collaborator. We suggest the excess mortality of African Americans can partially be explained by surgery-induced angiogenesis since the average age of diagnosis of AA is 46 years compared to 57 years for European-Americans. This excess first appeared in 1970s when mammography began. This is reported in Retsky et. al., Int J Surg 2007.
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Unusual for a cancer researcher, Retsky has a background in experimental physics, having received a PhD in physics from University of Chicago in 1974. His thesis project was to design and build a 100 kV scanning transmission electron microscope. This microscope could image single atoms on a carbon film. Retsky later worked in the electron beam technology field at Zenith Electronics in Chicago (fulfilling an obligation for supporting 5 years of graduate school) and Hewlett-Packard in Colorado Springs.
While at Hewlett-Packard, Retsky became interested in cancer research when a good friend's wife was diagnosed with cancer. A small informal research group consisting of Retsky, Robert Wardwell (the patient's husband), Victor Petrosky (H-P scientist) and Jack Speer, MD (the oncologist treating Wardwell's wife) studied breast cancer using computer simulation. Powerful H-P computers were available to the group. Retsky did the computer simulation since that was a common tool in his profession. The group published a paper (Speer et al, Cancer Research 1984) proposing that cancer growth includes periods of dormancy rather than the accepted continuous growth Gompertzian kinetics (damped exponential).
Due to a very strange circumstance, for 5 years Retsky had an engineering position at H-P that did not require all of his time, allowing him to read cancer research papers from the Penrose Cancer Hospital Library. He learned about cancer starting from the original papers. He knew where evidence was strong and where it was not. While evidence-based medicine is now a strong principle, it was not always so and some standard cancer practices were established at an earlier time.
Gradually Retsky became more interested in cancer research than electron optics. In 1987 H-P wanted to downsize and offered voluntary severance packages. Retsky took that and got a position as Research Professor in the department of Biology at the University of Colorado. He also was Visiting Professor alternate weeks for 6 months in the department of Medicine at University of Texas-San Antonio in the late William McGuire's group. He tested the accuracy of the computer simulation using UT's 5700 patient database and ended up with 4% error. A reference laboratory in Stratford, CT, wanted to offer the prognostic report free to their tumor marker clients. Retsky and his wife ended up moving to Connecticut to develop and help market the prognostic report. This project ended in 1994.
In November 1994, Retsky was diagnosed with stage 3 colon cancer. Rather than use the conventional Gompertzian-based chemotherapy regimen, with Dr. Hrushesky he designed a low-dose daily infusional protocol using the common colon cancer drug 5-fluorouracil. This virtually non-toxic therapy was continued for 2.5 years. This therapy is the forerunner of metronomic chemotherapy (see Browder et al Cancer Research 2000) - now in trials around the world. Retsky is disease-free and well beyond the 6-8 year period of risk of relapse in colon cancer.
In 1996, Retsky joined Dr. Folkman's lab on a part time basis. In addition to his breast cancer research, he still works in electron optics. Current patent applications are for 1) a new method of electron beam computed tomography and 2) a "Stars Wars" device for defense against ballistic missiles. The latter project resulted from patriotic fervor after 9-11.
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- Retsky MW, Demicheli R, Swartzendruber DE, Bame PD, Wardwell RH, Bonadonna G, Speer J, and Valagussa P. Computer simulation of a breast cancer metastasis model. Breast Cancer Research and Treatment, 45:193-202, 1997.
- M Retsky, R Demicheli and W Hrushesky. Premenopausal status accelerates relapse in node positive breast cancer: hypothesis links angiogenesis, screening controversy. Breast Cancer Research and Treatment, 65:217-24, Feb 2001.
- M Retsky, R Demicheli and W Hrushesky. Breast cancer screening: controversies and future directions. Current Opinion in Obstetrics and Gynecology. 15:1-8, 2003.
- Retsky M, Demicheli R and Hrushesky WJM. Does surgery induce angiogenesis in breast cancer? Indirect evidence from relapse pattern and mammography paradox. International Journal of Surgery 2005;3(3):179-187
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