Adjuvant Therapy Of Primary Breast Cancer Vi

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.

The results of randomized trials evaluating the use of early or adjuvant systemic treatment for patients with resectable breast cancer provide an eloquent rebuttal to those who would argue that we have made no progress in the treatment of cancer. Many of the tumors that we have been most successful in curing with chemotherapy and other newer forms of treatment are relatively uncommon. In contrast, breast cancer continues to be the single most common malignancy among women in the western world, is increasingly a cause of death throughout Asia and Third-World countries, and remains one of the most substantial causes of cancer mortality world wide. The use of mammography as a means of early detection has been shown to reduce breast cancer mortality by 25-35% among those popu lations in which it is utilized. The use of adjuvant systemic treatment in appropriate patients provides a similar (and additional) reduction in breast cancer mortality. Few subjects have been so systematically studied in the history of medicine, and it seems fair to conclude that the value to adjuvant systemic therapy in prolonging the lives of women with breast cancer is more firmly supported by empirical evidence than even the more conventional or primary treatments using various combinations ofsurgery and radiotherapy.

Adjuvant treatment is administered prior to or as follow up to surgical procedures for breast cancer. Proven success in using medical therapies allowing for breast conserving procedures or reducing risk of occurrence. Although there has been much progress towards a cure, including the introduction of new targeted therapies, metastasizing cancer remains highly incurable.

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.

The efficacy of adjuvant chemotherapy was first demonstrated in the early 1970's. Prolonged follow-up of these trials confirms the lasting improvement in overall survival with the administration of adjuvant chemotherapy. The early meta-analysis offers the practicing physician a good sense of the broad trends in adjuvant therapy (both chemotherapy and hormonal therapy), but falls short during periods of rapid changes in available agents or approaches. This volume deals with different views on the early overview. One view highlights therapeutic advances that have not yet been incorporated. Another view places the overview in context, contrasting the consensus recommendations with actual delivery of therapy in the community. While the overview provides meaningful guidelines for the patient with an 'average risk' early breast cancer, oncologists routinely struggle with patients at either end of the risk spectrum. In this volume, the use of neoadjuvant chemotherapy is looked at. This was initially reserved for patients with locally advanced or inflammatory disease. Adjuvant treatment decisions are based largely on the results of randomized clinical trials. necessarily unrepresentative of the general population of breast cancer patients. Another point is that in real life, clinical therapy frequently requires a series of negotiations between patient and physician, especially with the explosion of the Internet, which makes it easier for patients to find (mis)information.

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.