SBIR and STTR Success Story for
OncoMetrics*, Inc.

(Information Posted/Updated on 08/13/2007)

OncoMetrics*, Inc.
237 Strobel Road
Trumbull, CT  06611

Contact:    Michael Retsky, PhD
Phone:      203-452-1649
E-mail:      michael.retsky@childrens.harvard.edu
Web Site:  http://www.elopt.com

Project Title:  Precise breast cancer staging with an expert system
Related Award(s):  1R43CA65314
Technology Developed:
It appears that metastatic breast cancer does not grow continuously as previously thought but rather commonly includes periods of temporary dormancy and furthermore, surgery to remove the primary breast tumor often disturbs this dormancy and kick-starts growth. This is a very large effect in that 50% to 80% (increasing with tumor size) of all relapses in breast cancer are thus accelerated by surgery (1,2). Based on the timing of the relapses, we have predicted that dormant single cells are induced into division and also that surgery can induce angiogenesis (particularly in premenopausal nodel positive cases) of dormant micrometastases (3).

Key Words:  breast cancer, dormancy, surgery, angiogenesis, mammography, racial difference , bimodal relapse, chemotherapy.
Uses of Technology/Products/Service:
This work did not lead to a commercial success due to some internal problems unrelated to science. However this has developed into a far-reaching cancer research project. Two of the original researchers continue to pursue the results of this SBIR supported project at Harvard Medical School in Judah Folkman's laboratory and at the Milan National Cancer Institute in Italy.

Other Comments Related to Company's Success Story:
As a direct result of the research initiated by this grant, we developed and published a new theory of metastatic breast cancer growth and stimulation by primary surgery. This hypothesis explains a wide variety of breast cancer observations that were previously thought to be unrelated (4).

A few of these are listed below:

1) There is a bimodal pattern in relapses after surgery to remove a primary breast tumor. The early peak is at 18 months, there is a nadir at 50 months and a second broad peak at 60 months that extends for over 15 years. This pattern (confirmed in 12 independent databases and identified in 5 others) is not predicted based on any prevailing theory of breast cancer. 2) In general, early detection of breast cancer using mammography is more effective for women age 50-59 than for women age 40-49. Most telling, in trials conducted before the use of adjuvant chemotherapy there was a very disturbing excess mortality among screened women compared to unscreened controls for women age 40-49 in the first 6-8 years of clinical trials. This did not happen for women age 50-59. Based on our Milan data, we calculated the effect of surgery induced angiogenesis and it agreed in timing and magnitude with the trial data (3,5,6).

3) Adjuvant chemotherapy is by far most effective for premenopausal node-positive patients than for any other category of patients. According to our explanation, surgery-induced angiogenesis provides a short window just post surgery when metastases are growing very rapidly and are thus highly chemosensitive. Adjuvant chemotherapy was empirically determined to be most effective in the 6-month period after surgery and the benefit was greatest for premenopausal node-positive patients. Two papers published in 2004 proposing this explanation have been downloaded over 20,000 times (7,8). This effect might explain why chemotherapy can cure some patients in early stage disease but is only palliative in late stage disease.

4) Despite a lower incidence, African Americans (AA) have higher mortality than European-Americans (EA) from breast cancer. It is unlikely to be explained by a 2-tiered level of access to competent medical care since while there is excess AA mortality under age 57, there is reduced mortality above age 57. If we blame the excess mortality under age 57 on less access to quality medical care, then we must attribute the reduced mortality over age 57 to reduced access to quality medical care (reductio ad absurdum). We noted that AA are diagnosed with breast cancer at an average age of 46 years while it is 57 years for EA. The excess mortality of AA over EA is at least partly explainable by the difference in age at diagnosis and the improved benefit of early detection for postmenopausal women (9,10).

5) Breast cancer removal by surgery has been done since biblical times and remarkably was often successful despite lack of sterilization and anesthesia. According to Celsus (30 BC - 38 AD), “First there is the cacoetheses, then carcinoma without ulceration, then the fungating ulcer… None can be removed but the cacoetheses; the rest are irritated by every method of cure. The more violent the operations the more angry they grow.” We apparently rediscovered something that was known to surgeons 2000 years ago (11).

A recent development is that we now suggest a new method for treating early stage breast cancer called dormancy stabilization and retention (patent pending) (12). References (Many of these papers are available at http://www.elopt.com):

1. 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. 2. Demicheli R, Retsky M, Swartzendruber D and Bonadonna G. Proposal for a new model of breast cancer metastatic development. Annals of Oncology, 8:1075-1080, 1997. 3. 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. 4. M Retsky, R Demicheli, WH Hrushesky, M Baum, I Gukas, Can surgery provoke the outgrowth of latent breast cancer? A unifying hypothesis. Breast-Cancer-Online 10(4) 2007. 5. M Retsky, R Demicheli and W Hrushesky. Breast cancer screening: controversies and future directions. Current Opinion in Obstetrics and Gynecology. 15:1-8, 2003. 6. 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. 7. M Retsky, G Bonadonna, R Demicheli, J Folkman, W Hrushesky, P Valagussa. Hypothesis: Induced angiogenesis after surgery in premenopausal node-positive breast cancer patients is a major underlying reason why adjuvant chemotherapy works particularly well for those patients. Breast-Cancer-Research, 2004, 6:R372-R374 (14 May 2004). http://breast-cancer-research.com/content/6/4/R372 8. R Demicheli, G Bonadonna, WJM Hrushesky, MW Retsky. P Valagussa. Menopausal status dependence of the timing of breast cancer recurrence following primary tumour surgical removal. Breast Cancer Research 2004, 6:R689-R696 . http://breast-cancer-research.com/content/6/6/R689 9. M Retsky, R Demicheli, I Gukas and W Hrushesky. Enhanced surgery-induced angiogenesis among premenopausal women may partially explain the breast cancer excess mortality of blacks compared to whites. In press, International Journal of Surgery. 2007. 10. R Demicheli, M Retsky, W Hrushesky, M Baum, I Gukas and I Jatoi, Racial disparities in breast cancer outcome: adding host-tumor interaction biology to socio-economic inequalities, In press Cancer, August 2007. 11. M Baum, R Demicheli, W Hrushesky and M Retsky. Does surgery unfavorably perturb the “natural history” of early breast cancer by accelerating the appearance of distant metastases? European Journal of Cancer 2005 Mar;41(4):508-15. Epub 2005 Jan 18. 12. M Retsky, I Gukas and W Hrushesky, Dormancy stabilization and retention: New method hypothesized for treatment of early stage breast cancer. July 2007. Published online at http://www.discover8.com