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."

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."

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.

The book gives an overview of the clinical developments in the use of bisphosphonates in clinical oncology. The first part pre sents the composition, physiology, and pathophysiology of bone. Next is a section giving insight into mechanisms of bone resorp tion, bone formation, and bone remodeling, a field in which I was most influenced by O. L. M. Bijvoet and H. Fleisch. The sec ond part summarizes the pharmacological treatments for disor ders of bone remodeling. The clinical aspects of tumor-induced hypercalcemia and its management are described in detail, in cluding our first prospective randomized crossover study testing pamidronate versus mithramycin. The bisphosphonates were in troduced in clinical oncology by endocrinologists. The same was true for our institution in 1986, when P. Burckhardt proposed testing pamidronate in the above-mentioned trial in his institu tion (CHUV) and in our department. The impressive results ob tained in the hypercalcemia trial stimulated our interest, and we actively investigated the use of pamidronate to counteract osteo lytic bone destruction in cancer patients. These investigations are presented and discussed in the third part. They represent the interdisciplinary work involving many co-workers of the Depart ment of Internal Medicine C and other institutes of the Interdis ciplinary Oncology Center St. Gallen (IOSG), which I was privi leged to chair for 10 years. Initially, a pharmacokinetic study was performed in order to optimize and facilitate the administration of the drug to patients with malignant osteolytic bone disease."