William S. McGuire Memorial Lectureship Award given to Larry Norton, MD, at San Antonio Breast Cancer Conference, December 11-14, 2008
Many research presentations made during the course of the 2008 San Antonio Breast Cancer Symposium (SABCS) held December 11-14 referenced BCRF support. This year's recipient of SABCS's William S. McGuire Memorial Lectureship Award was BCRF Scientific Director, Larry Norton, MD, who was introduced to the overflow crowd in San Antonio by Symposium co-Director and BCRF grantee C. Kent Osborne, MD, of Baylor College of Medicine. Dr. Osborne emphasized Dr. Norton's reputation as a great mentor to many physician researchers, his committed patient advocacy in addition to his clinical practice and research accomplishments, and how his scientific leadership at BCRF has led to the identification of many research advances at their earliest stages.
Dr. Norton's lecture is now available online:
1) Go to the SABCS
2) Click on 'Streaming Webcasts'
3) Click Online Presentations, Video or Audio
4) Click Fri. Dec. 12
5) Click McGuire Lecture
Dr Norton has devoted his research career to understanding the basic biology of cancer, the mathematics of tumor causation and growth, and development of better approaches for cancer management. He is perhaps most specifically identified with the therapeutic approach called "dose density" or "sequential dose density." This approach is based on a mathematical model developed by Dr Norton and colleagues, which is designed to maximize killing of cancer cells while minimizing toxicity.
Dr Norton presented his lecture on Friday morning, discussing modern molecular medicine and how it is changing our view of cancer. Dr Norton began his presentation with an enumeration of things that we "know" about breast cancer: that cancer development is an orderly progression; that cancer is systemic rather than local; that histologic grade is prognostic; that molecular profiling works; that in combining chemotherapy drugs, the total is often more than the sum of the parts; and that adjuvant therapy can cure patients. Unfortunately, there are troublesome observations that appear to contradict each of these in some cases. For example, if the progression of cancer is orderly, why do we sometimes find distant metastases in patients who are node-negative? If breast cancer is systemic, why does the addition of localized radiotherapy to breast-conserving surgery result in reduced mortality from metastasis? Why are histologic grade, tumor size, and lymph node status all strongly prognostic, when they represent such different biological processes?
Dr Norton hypothesized that many of the apparent contradictions in our knowledge base about breast cancer behavior may be explained by the re-seeding of mammary tumors by circulating tumor cells. Cells that escape to the circulation can seed in distant sites, but may also seed into other parts of the breast or re-seed into the site of the primary tumor itself. This would explain the occasional appearance of tumor foci several centimeters away from the clean margins of the primary tumor, and also explain how radiation after conservative surgery might improve rates of local recurrence and mortality. It would also explain the dendritic appearance of fast-growing aggressive tumors, if one supposes that these tumors are composed of multiple re-seeding foci, essentially comprising a bundle of small tumors. Growth kinetics of these compound tumors would be distinct, and different genes would be involved in their tumorigenic evolution. The hypothesis that cancer is a disease of self-seeding could increase our understanding of the apparent contradictions in tumor behavior and lead to a rethinking of current therapeutic strategies.
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