Hans-Jorg Senn – författare

This volume contains the main proceedings of the fourth international conference on "Cancer Prevention 2006," which was held during February 16–18, 2006, in St. Gallen, Switzerland. Written by international experts in the field, the book comprises a comprehensive update on the most recent developments in the upsurging fields of molecular biology and cancer genetics and their interactions with clinical epidemiology and cancer prevention at various levels: genetic/biologic predisposition and definition of high-risk groups; preclinical models and tumor prevention; prospects of surrogate endpoints and biomarkers; progress in imaging and detection of neoplastic precursor lesions; problems with Cox-2 inhibitors in tumor chemoprevention; primary and secondary prevention of gynecological, breast, gastrointestinal and genitourinary cancers. In addition, the future prospects of cancer chemoprevention are discussed.

More than 180 participants and experts from 31 countries met for the fifth time in 10 years in St. Gallen, Switzerland for a 3-day conference to discuss important current issues of clinical cancer prevention. The meeting was again organized and co-sponsored by St. Gallen Oncology Conferences (SONK). While SONK has been extremely successful in organizing large international c- gresses on “Primary Therapy of Early Breast Cancer” as well as “Supportive Care in Cancer” for more than 20 years, the idea of promoting interdisciplinary, clinically oriented meetings on cancer prevention is a more recent and not yet generally accepted and w- comed concept in modern oncology. Since today’s medical expenses are soaring and me- cal research budgets are stagnating or even being cut, neither politicians nor industry is willing to risk an additional unpredictable channel of expenses, such as that demanded by clinical cancer prevention efforts! In Switzerland—and we fear in many other parts of the globe—some 97%–98% or even a greater percentage of health budgets is spent for curative and palliative/rehabilitative m- icine. Since a meager 2%–3% of national health budgets is for preventive medicine, even less than that proportion is specifically allocated for cancer prevention. When the money for “curing and caring” for the diseased populace runs short, there is likely not much left for partly controversial disease prevention in the (still) healthy part of the population.

This book is based on presentations by some of the world’s leading experts at the Sixth International Conference on Clinical Cancer Prevention, held in St. Gallen, Switzerland, during March 2010. The main themes are the latest advances in the prevention of breast and prostate cancer and the role of infection in the development of liver and gastric cancer. Special emphasis is given to perspectives on the chemoprevention of breast cancer, as the conference included an international consensus meeting on this subject. New research findings are presented and potentially more effective cancer prevention strategies are discussed, with careful consideration of controversies. The expertise of the contributors encompasses genetics and microbiology, epidemiology, and health economics, as well as clinical cancer prevention. This book will be of interest to all who wish to learn about the most recent progress in combating the development of cancer.

This book is based on presentations by some of the world’s leading experts at the Sixth International Conference on Clinical Cancer Prevention, held in St. Gallen, Switzerland, during March 2010. The main themes are the latest advances in the prevention of breast and prostate cancer and the role of infection in the development of liver and gastric cancer. Special emphasis is given to perspectives on the chemoprevention of breast cancer, as the conference included an international consensus meeting on this subject. New research findings are presented and potentially more effective cancer prevention strategies are discussed, with careful consideration of controversies. The expertise of the contributors encompasses genetics and microbiology, epidemiology, and health economics, as well as clinical cancer prevention. This book will be of interest to all who wish to learn about the most recent progress in combating the development of cancer.

This RRCR-conference-volume marks "number six" in a 20-year evolution of international conferences on the adjuvant therapy of primary breast cancer. Starting in 1978, a handful of some 80 en­ thusiastic breast cancer surgeons and oncologists, met in a se­ cluded mountain resort near st. Gallen in Eastern Switzerland, to exchange their early data of some pioneer trials on adjuvant sys­ temic therapy of early breast cancer, and to correlate their future research efforts to overcome the frustrating prognostic stagna­ tion of this dominant neoplastic disease in Western females dur­ ing the past decades. Repeated every 3-4 years, these St. Gallen International Conferences on Adjuvant Therapy of Primary Breast Cancer have continuously grown in numbers of partici­ pants and in normative, therapeutic influence by being published in major oncology journals [1-3], the last (6th) conference hav­ ing taken place from February 25-28, 1998 with more than 1800 attendees from over 50 countries worldwide. What is the fascination of adjuvant therapy in primary (early) breast cancer, and what has changed,during the last 3 years since March 1995, to justify another international gathering of this size, and of the world''s leading experts in the field? There is no question, that providing even more effective care and designing appropriate recommendations for the multitudes of patients with so-called early breast cancer or at high risk of developing the disease, remain highly important public health goals.

Hans-Jorg Senn H.-J. Senn (~) Center for Tumor Detection and Prevention, Rorschacherstr. 150, CH-9006 St. Gallen, Switzerland Clinical oncology has centered mainly on developing new strategies and a multitude of new drugs for fighting relapsing and progressive cancer during the last two decades. Furthermore, it has done this with respectable success in quite a number of neoplastic diseases such as acute leukemias and sarcomas in pediatric patients and certain types of aggressive lymphomas, as well as se­ lected solid tumors such as testicular cancer and choriocarcinoma in adult age. Curatively intended adjuvant chemo-and endocrine-therapies of several "main killers" among prevalent cancer types, especially breast and colon can­ cer, have also become successful and health-politically meaningful therapeutic targets [1, 2]. However, the net gain in "cure" of these (mostly pharmacologic) therapeu­ tic approaches has to be realistically judged as having a moderate impact on the cancer problem as a whole, and the mortality rate of the most frequent tu­ mor types, which are prevalent in adult life, has with very few exceptions not been substantially decreased over the past two to three decades. Increasingly, health politicians, epidemiologists, and medical journal editors are asking for alternative strategies of lowering cancer incidence and increasing survival, ventilating new and hitherto mostly neglected areas of research such as pri­ mary and secondary cancer prevention.

We often hear physicians, health care professionals, poli­ ticians, and patient advocates that "nothing has happened in the treatment of breast cancer," since patients with breast cancer, the most frequent neoplastic condition in women in industrialized countries, are continuing to suffer relapse and succumb to this dreadful disease! This negativistic attitude does not seem to be justified, but, why is the transmission of clinical trial results into general practice, and with it progress, such a slow process? After many decades of frustrating stagnation of long-term survival expectations, in all stages of early, oper/lble breast cancer treated only by surgery and locoregional radio­ therapy, adjuvant systemic therapy (chemo- as well as endocrine treatments) clearly showed to significantly benefit in terms of disease-free and overall survival. This evolution has been extensively expounded on by the Worldwide Oxford Overview and the Expert Consensus Panel at the fourth International Conference ''on Adjuvant Therapy of Primary Breast Cancer in St. Gallen (Early Breast Cancer Trialists'' Collaborative Group 1992; Glick et al. 1992). What has happened since then? During the past 3-5 years, several new concepts and treatment strategies have emerged and have been studied in various major breast cancer groups and treatment centers worldwide. Some of these can already be considered to assist in the primary treatment of operable breast cancer today, while others are . still undergoing clini,cal trials for better definition of their practical usefulness.

H.-J. Senn Adjuvant Chemotherapy (ACT) of breast cancer has now emerged as one of the controversial su):>jects in clinical and also experimental oncology. Driven by growing frustration about stagnating cure rates in breast cancer [1,4] and stimulated by elegant demonstration of highly curative effects of adjuvant systemic therapy in animal models [6, 11] and in several childhood neoplasias [15], researchers introduced ACT to the primary treatment of breast cancer with great hope some 15 years ago. After a first wave of isolated "historic" trials with generally limited but in one case remarkable success [5, 9], a second generation of ACT studies was initiated by NSABP investigators and oncology centers in Europe [2, 6, 13]. These trials were well conducted statistically and diagnostically, and all in the early 1970s included a surgical control arm. Early and intermediate beneficial effects on relapse-free survival (RFS) after 2-3 years median observation time then prompted a whole series of ACT studies in breast cancer. These "third-gener­ ation" studies usually regarded some positive influence of ACT as a given fact, dropping surgical control regimens and comparing different ACT regimens, hopefully in a prospective, randomized way 1984 Fig. 1. The mushrooming of adjuvant studies in breast cancer XII Introduction [reviews in 3, 14]. The "mushrooming" of ACT studies in breast cancer during the last 10 and especially 5 years is demonstrated in Fig. 1, and it gets really cumbersome even for the insider to keep on top of the multitude of sometimes conflicting data.

The symposium on supportive care in cancer patients, which took place in St. Gallen, Switzerland, on February 18-21, 1987, wel­ comed renowned experts in the field and more than 600 partici­ pants from 25 countries with the aim of stimulating discussion on how to improve our professional skills and personal attitudes to­ ward cancer patients in all stages of their disease. Why did we or­ ganize such a symposium on supportive care in cancer patients? Recent decades have witnessed remarkable success in cancer treat­ ment, and we have learned how to cure a finite number of neoplas­ tic diseases. Some malignant tumors that previously entailed high fatality rates, such as leukemias, lymphomas, and testicular can­ cers, can now be cured, even when at an advanced stage. Yet it seems to many that our struggle to improve results and to fight death from cancer has also imposed greater toxicity on patients. Conventional scientifically based oncology has only recently made adequate efforts to improve the subjective quality of life of cancer patients, for example through prophylaxis against emesis, nausea, and scalp hypothermia, pain control and the development of psy­ chosocial support structures. The search for less toxic and yet equally effective treatment measures has not been one of our pri­ mary goals in the past. Supportive care has always been part of nurses'' professional aim, even though many have not known how best to offer it.

The ultimate "consumer" of the data presented at conferences on the primary treatment of operable breast cancer is the patient, and when, as in this disease, the benefits of therapy are relatively mod­ est, the availability and interpretation of the data from trials be­ comes an issue of primary importance. The effects of present treat­ ment are in fact such that more patients relapse despite therapy than are estimated to benefit from it. It is, therefore, extremely dif­ ficult for the physician to recommend unequivocally one particular adjuvant treatment modality for the vast population of women with breast cancer. The interpretation of results from clinical research-oriented pro­ grams is constantly applied, however, in the treatment of breast cancer patients outside of clinical trials. From presented or publish­ ed data, many physicians extrapolate indications for the use of a given treatment regimen for their patients, perceiving it as the "best available therapy. " It is essential that the "best available therapy" be selected individually for each patient. However, considering the modest effect of treatment upon outcome, it is imperative that those who provide the data - those who are involved in both pa­ tient care and clinical research - make it known that the best cur­ rent treatment for the population of breast cancer patients is avail­ able within the framework of clinical trials. In this way not only present-day patients but also future ones will derive the greatest benefit.

The second international symposium on "Supportive Care in Cancer Patients" took place March 1-3, 1990-again in St. Gallen in eastern Switzerland. It was an honor once more to welcome dozens of internationally recognized experts in the field and more than 800 participants from over 30 countries around the world: Australia, Canada, China, USSR, USA and many countries in Europe. The international nature of the grade facilitated lively and exciting contributions and critical discussions, aimed at fostering professional knowledge and skills and rethinking our personal attitudes toward cancer patients in all stages of their disease. Cancer patients need various types of tailored support, whether during active initial (curative) therapies, in phases of worrying relapsing disease, or during the demanding terminal stage of their illness. The symposium tried to bridge the strange "gap" between "curative" and "palliative" cancer care: it must be our aim to be and remain "supportive" for our patients during both curative and palliative treatment strategies! This requires extended knowledge and even more and flexible professional skills. The symposium was designed to promote improved approaches that are helpful and supportive for all our oncology patients, not just for a selected disease-or stage­ dependent minority.

Advances in breast cancer research, achieved through the progress of knowledge and development of new therapies, have been translated into improved quality of care for breast cancer patients. Clinical investigations and clinical trials have made the largest contribution to the body of knowledge that finds its way to the patient. Never before during the past decades of management of breast cancer has there been such a fruitful intellectual cross-fertilization of ideas among individuals involved in the generation of hypotheses, basic research, development of drugs and treatments, conduct of clinical trials, and statistical evaluation - the results of all of which are now translated into progress in clinical care. Even issues such as the quality of life of breast cancer patients, once the domain for few, are now being openly addressed by trials and discussed in a much broader forum. The IVth International Conference on the Adjuvant Therapy of Primary Breast Cancer, also known as the st. Gallen Conference, was again attended by more than 800 scientists and clinicians interested in this broad spectrum of breast cancer research and the interactions between such diverse fields of interest and specialties as cancer pathology, molecular biology, and psychosocial oncology. This volume collects findings and conclusions presented at the conference.