Bisphosphonates in adjuvant treatment of early breast cancer

Abstract

Adjuvant breast cancer is a challenging field for all of us being involved. What have we achieved in the past years? Where are new starting points to improve overall survival for more and more patients suffering from this potentially life-threatening disease? Up to 90% of patients with early detected breast cancer are alive after 5 years provided they receive adequate treatment. Adjuvant endocrine therapy for most of these hormone-responsive tumors is a standard treatment and clearly improves overall survival. What about patients at the other end of the spectrum, the patients with hormone-receptor-negative, early disease and other high risk factors? Chemotherapy in combination with trastuzumab, if indicated, will also provide improved overall survival. However, overall survival curves do not reach a plateau. There are less early relapses but still loco-regional and contralateral recurrences as well as distant metastases do occur even after longer follow up. Our goal must be to increase overall survival and reach a plateau at a very high level and to cure more patients. Which new targets may help us to proceed a step forward? Years ago, bone metastases gave us a first clue of the influence of bone metabolism on metastasis development. We investigated the mechanisms of bone metastases in more detail and developed several generations of bisphosphonates. This group of drugs proved to be useful in the treatment of bone metastases. The bisphosphonates might be more than a class of supportive drugs restricted to improve life with bone metastases. Bisphosphonates and other agents may be able to prevent bone metastases by indirect and direct mechanisms and hence improve disease-free and overall survival of early breast cancer. There was groundbreaking news about the antitumor activity of bisphosphonates for patients with early breast cancer at the ASCO Meeting 2008 and SABCS 2008. The ABCSG-12 and ZO-FAST trials showed promising results with less metastases, longer disease-free and overall survival as well as a higher pCR rate if zoledronic acid (ZOL) was given in a neoadjuvant setting. These efficacy data indicate that an early use seems to be superior to a delayed use of the drug. ABCSG-12 and ZO-FAST confirm older data indicating that adjuvant oral clodronate may improve outcome in early breast cancer. Encouraging data − but do they already provide sufficient evidence to recommend the routine use of adjuvant bisphosphonates in early breast cancer for all patients? In this supplement, we summarize the presentations and discussions of the Elsevier Professional Education Symposium ‘Bisphosphonates in Adjuvant Treatment of Early Breast Cancer’ held on the 10th of March 2009 in St. Gallen, Switzerland.