Less is More in the Management of Breast Cancer

According to a study reported in the Journal of the American Medical Association, a randomized clinical trial that compared axillary lymph node removal to no lymph node removal in patients with node-positive breast cancer, there was no advantage for the more aggressive lymph node removal in terms of survival. The study reported by principal investigator Armando Giuliano has created a stir in the surgical, radiation and medical oncologic communities.

But, in the global scheme of breast cancer management, it really should not have.

The history of breast cancer management is one of diminishing returns. In the beginning of the turn of the last century, breast cancer was managed by the Halsted radical mastectomy. This procedure removed the breast, lymph nodes and pectoral muscle, skeletonizing the chest wall. Following that, Hagenson, Crile and other early pioneers documented the equivalence of the Halsted technique and the modified radical mastectomy. Decades later, Veronese at the National Cancer Institute of Italy proved that a quadrantectomy was equivalent to a modified radical mastectomy. This gave rise to the lumpectomy and finally the lumpectomy with sentinel lymph node dissection.

What we have learned, painfully, is that breast cancers have a trajectory all their own. Those tumors with a propensity for dissemination are likely to progress despite aggressive surgery and the associated morbidity and disfigurement while those tumors unlikely to recur cannot possibly benefit from more therapy. To some degree the outcome was independent of the aggressiveness of the surgery.

For years, tumor biologists have recognized that the process of dissemination and metastasis can begin when some cancers are less than 1/8 cm3 in volume — well below the level able to be detected by most diagnostic tools. What Dr. Giuliano’s study has shown us is that cancer biology determines the cancer outcome. The scalpel blade, however sharp, is a blunt instrument in the management of micro-metastatic disease. The cure of this and other solid tumor malignancies will increasingly depend upon effective systemic therapies and judicious use of local measures. Recognizing the fundamental role of systemic management, optimization of drug selection becomes only that much more important.

About Dr. Robert A. Nagourney
Dr. Nagourney received his undergraduate degree in chemistry from Boston University and his doctor of medicine at McGill University in Montreal, where he was a University Scholar. After a residency in internal medicine at the University of California, Irvine, he went on to complete fellowship training in medical oncology at Georgetown University, as well as in hematology at the Scripps Institute in La Jolla. During his fellowship at Georgetown University, Dr. Nagourney confronted aggressive malignancies for which the standard therapies remained mostly ineffective. No matter what he did, all of his patients died. While he found this “standard of care” to be unacceptable, it inspired him to return to the laboratory where he eventually developed “personalized cancer therapy.” In 1986, Dr. Nagourney, along with colleague Larry Weisenthal, MD, PhD, received a Phase I grant from a federally funded program and launched Oncotech, Inc. They began conducting experiments to prove that human tumors resistant to chemotherapeutics could be re-sensitized by pre-incubation with calcium channel blockers, glutathione depletors and protein kinase C inhibitors. The original research was a success. Oncotech grew with financial backing from investors who ultimately changed the direction of the company’s research. The changes proved untenable to Dr. Nagourney and in 1991, he left the company he co-founded. He then returned to the laboratory, and developed the Ex-vivo Analysis - Programmed Cell Death ® (EVA-PCD) test to identify the treatments that would induce programmed cell death, or “apoptosis.” He soon took a position as Director of Experimental Therapeutics at the Cancer Institute of Long Beach Memorial Medical Center. His primary research project during this time was chronic lymphocytic leukemia. He remained in this position until the basic research program funding was cut, at which time he founded Rational Therapeutics in 1995. It is here where the EVA-PCD test is used to identity the drug, combinations of drugs or targeted therapies that will kill a patient's tumor - thus providing patients with truly personalized cancer treatment plans. With the desire to change how cancer care is delivered, he became Medical Director of the Todd Cancer Institute at Long Beach Memorial in 2003. In 2008, he returned to Rational Therapeutics full time to rededicate his time and expertise to expand the research opportunities available through the laboratory. He is a frequently invited lecturer for numerous professional organizations and universities, and has served as a reviewer and on the editorial boards of several journals including Clinical Cancer Research, British Journal of Cancer, Gynecologic Oncology, Cancer Research and the Journal of Medicinal Food.

One Response to Less is More in the Management of Breast Cancer

  1. The Surgical Specimen Is the Personalized Part of Personalized Cancer Medicine. In this dawning era of molecular medicine, surgeons and pathologists are playing a more pivotal role in cancer medicine. They are the custodians of the specimens and therefore the molecules that represent the personalized part of personalized cancer medicine. Surgeons will continue to cure cancer with greater success rates through earlier detection and excision, but as the custodians of the tissue, they will also be central to improving cancer management through molecularly targeted interventions.

    As we enter the era of personalized cancer medicine, it is time to take a fresh look at how we evaluate treatments for cancer patients. More emphasis is needed matching treatment to the patient. Patients would certainly have a better chance of success had their cancer been chemo-sensitive rather than chemo-resistant, where it is more apparent that chemotherapy improves the survival of patients, and where identifying the most effective chemotherapy would be more likely to improve survival.

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