By Marilyn Zivian
The 2007 Breast Cancer Symposium: Integrating Emerging Science Into Clinical Practice provided an opportunity for people working in breast cancer to learn about and raise questions concerning research developments relevant to treatment of the disease. Held in San Francisco in September, the symposium largely focused on translational research, i.e., research with the goal of determining how basic scientific findings may be best applied to the clinical treatment of patients. The symposium was cosponsored by the American Society of Breast Diseases, the American Society of Breast Surgeons, the American Society of Clinical Oncology (ASCO), the American Society of Therapeutic Radiology and Oncology, the National Consortium of Breast Centers, Inc., and the Society of Surgical Oncology.
The 33 oral presentations at the symposium were divided among the following eight topics: the role of estrogen in breast cancer, the impact of radiation on long-term survival, current controversies in treatment and screening, clinical and research issues in profiling breast cancer patients, local and regional management of metastatic breast cancers, HER2-positive breast cancer, disparities in incidence rates and care, and the use of preoperative therapy. In addition there were 293 poster presentations that more or less fit into the following four categories: the biology of risk and prevention, detection and diagnosis, epidemiology and biology, and treatment. A small set (14) of the posters was also presented orally. Clearly a great deal of information—more than many people (including myself) could absorb—was provided for the more than 1,200 individuals who attended the symposium (abstracts and video presentations are available online at www.asco.org).
Unlike other conferences that are primarily research focused, the goal of this symposium was not to present and publicize the results of leading-edge scientific research or major breakthroughs (although there were a few hints, as usual at cancer conferences, of exciting things to come in the future). Instead, the conference attempted to bring the latest in relevant and useful scientific results on the screening, evaluation, and treatment of breast cancer to the attention of medical, surgical, and radiation oncologists—and all other health care providers and parties with an interest in breast cancer therapy.
According to the presenters, this was the first symposium of its type, and I found it both informative and professionally engaging. First, as a woman living with breast cancer, I always want to know what is going on in the field. And, second, as a psychologist who herself was trained and who has trained others in what is known in our field as the scientist/practitioner model, I was curious about how well the symposium’s goal of bringing together scientists and practitioners in order to inform clinical practice would be met.
According to the scientist/practitioner model, in order to be a good clinician, one must also be a well-trained scientist and vice versa; to be a good scientist, one must be a well-trained clinician. Furthermore, this training will provide those who are both clinicians and scientists the opportunity to make important contributions to the field. The idea is that clinical experience with patients will provide scientific direction and influence interpretations of scientific results. And, in turn, meaningful scientific results will inform changes in clinical practice. Thus, scientific and clinical practice should drive each other forward. Most important, from the perspective of a patient, meaningful scientific results should be quickly, accurately, and easily incorporated into clinical practice.
The emphasis placed on translational research throughout the two-day symposium seemed to be not only an attempt to bring the latest research results to the attention of breast cancer clinicians and thus to give them the opportunity to incorporate the latest results into their treatment decisions, but also an attempt to give breast cancer clinicians the chance to bring their concerns about patient treatment directly to breast cancer researchers—a kind of scientist/practitioner model, if you will.
I can’t imagine a better example of the scientist/practitioner model in practice than the career of physician Daniel F. Hayes, the first recipient of the ASCO Gianni Bonadonna Breast Cancer Award and Fellowship. The award, which was announced at the symposium, was given to Hayes in recognition of his outstanding contributions as an educator and mentor. As a scientist and researcher, he emphasizes breast cancer research that translates findings into practice and bridges the gap between the laboratory and the clinic. In addition to his contributions as an educator, mentor, scientist, and researcher, Hayes has also lectured and published extensively on the management of breast cancer patients.
The desire and drive to be able to tailor breast cancer therapy to the many individual differences that exist among breast cancer patients was another theme unifying much of the research presented at the symposium. Hayes’s research was no exception. Together with his longtime colleague, physician Donald Kufe, Hayes published the first reports concerning the development of the CA15-3 blood test, which is used to monitor a patient’s response to breast cancer treatment and to watch for breast cancer recurrence. He is an internationally recognized leader in the use of this and other tumor markers, such as HER-2, to individualize cancer treatment.
Since the identification of new tumor markers and the evaluation of their role in individualized patient treatment seems to be the goal of much of future breast cancer research, I thought I would describe them and briefly discuss how they may be used to plan an individual’s treatment. What I report relies primarily on information in Hayes’s presentation and publications on this topic.
Tumor markers are changes that occur in molecules, substances, or processes in the bodies of patients with precancerous or cancerous conditions. These changes may be found in tissue samples, in cells that have been exfoliated, or in body fluids, such as blood, urine, or sputum. Tumor markers can be used to predict the risk of disease, to screen for disease, to make diagnoses, to predict the risk of relapse following primary therapy, and to predict the risk of progression or death from metastasis. In addition, measurements of tumor markers taken periodically over time may be used to monitor a patient’s response to treatments.
Generally speaking, tumor markers fall into three broad categories: they may be prognostic, predictive, or both. Prognostic markers can be used to predict the likelihood of a cancer to proliferate and spread; they help distinguish more aggressive from more indolent (slow to develop) primary cancers. Predictive markers indicate a cancer’s relative sensitivity or resistance to specific treatments or interventions. Markers that are both prognostic and predictive can be used to estimate the probability that a cancer will or will not spread and the probability that the cancer will or will not respond to a particular treatment. Finally, some are strong prognostic tumor markers, others are weak. The same is true of predictive tumor markers–some are strong, others are weak.
Important markers for breast cancer include the presence of axillary lymph node metastases (spread of cancer to lymph nodes in the armpit), one of the strongest markers for increased risk of relapse, tumor grade (the degree of abnormality of cancer cells), a moderately strong marker for increased risk of relapse, and the absence of an estrogen receptor, a weak prognostic marker for increased risk of relapse. Estrogen receptor-rich breast cancer is a strong predictive marker for positive response to treatment with tamoxifen.
So how do clinicians use marker information to determine an individual patient’s treatment? Say that Patient A is a 45-year-old woman with lymph-node-negative (no known axillary lymph node metastases), estrogen receptor-rich, low tumor grade, invasive breast cancer. The presence of the estrogen receptor-rich tumor marker means that treatment with adjuvant hormonal therapy (e.g., tamoxifen or an aromatase inhibitor) will significantly decrease her risk of recurrence and death. Although additional treatment with systemic chemotherapy would further reduce her risk, her prognosis is so good that any additional benefit she might get from chemotherapy would probably be outweighed by the treatment’s toxicity.
Clinicians may also vary their recommendations for more or less therapy, depending on tumor markers. For instance, a patient with 10 positive axillary lymph nodes will likely be prescribed a more prolonged or intense course of adjuvant systemic chemotherapy than a woman with one positive lymph node.
Hoping to find better and more accurate tumor markers that will allow even greater individualization of clinicians’ treatment plans for their patients, complex combinations of genes are currently being assessed as prognostic and/or predictive breast tumor markers. For example, Hayes described an ongoing trial of a genetic test that looks at a combination of 16 cancer genes and five reference genes to produce a score that can be used as a predictor of breast cancer recurrence over a 10-year period. (For more on genetic tests, see “Hold the Chemo: Who Will Benefit and Who Won’t” in BCA Newsletter #93, October/November 2006.)
Also in attendance was physician Gianni Bonadonna, the man for whom the award that Hayes received was named. Bonadonna is considered to be one of the most important figures in modern-day medical oncology. His achievements include ground-breaking research in the adjuvant treatment of breast cancer and the development of the combination chemotherapy regimen that is still considered to be the gold-standard treatment for Hodgkin’s Disease.
Although he appeared to be quite ill, Bonadonna gave a short presentation in which he stressed the importance of “improving the alliance between patients and doctors.” It is hard to imagine a meaningful alliance existing between patients and their doctors unless patients understand why their doctors have recommended a particular treatment plan for them—especially since patients must feel comfortable with and ultimately agree to the treatment plan. The world of breast cancer treatment is becoming ever more complex. Often the reasons oncologists choose a particular treatment plan can seem quite mysterious to their patients. I hope that this discussion about tumor markers will remove some of the mystery.
Was the 2007 breast cancer symposium successful? The frequency with which members of the audience asked presenters questions such as “So, Dr. B, if patient X presented to you with x1, x2, and x3, but not y1, do you still think that treatment Y is appropriate for her?” made it clear that the symposium was at least somewhat, if not very, successful in bringing relevant research results to the attention of breast cancer clinicians and in giving them the opportunity to raise concerns about patient treatment directly with breast cancer researchers.
Finally, in the interest of “improving the alliance between doctors and patients,” perhaps the 2008 breast cancer symposium should be entitled: Translating Emerging Science for Breast Cancer Patients. Patients, too, need the opportunity to learn about the latest research results and to raise their concerns about treatment directly with breast cancer researchers.