Adjuvant Bisphosphonates in Breast Cancer Treatment

Abstract

Several solid tumors like breast cancer tend to spread to the bone, where the microenvironment is especially receptive to the tumor by special interactions between bone cells and tumor cells. Bone metastases often lead to skeletal-related events with significant morbidity and mortality. The therapy of bone metastases and osteoporosis with bisphosphonates (BPs) has been established many years ago as a standard treatment. In the adjuvant setting, cancer treatment-induced bone loss is a frequent cause of morbidity, and prevention and treatment of this condition with BPs and the monoclonal antibody denosumab are also well established. Besides postmenopausal patients, several studies including 2 larger studies by the Austrian Breast and Colorectal Cancer Study Group (ABCSG) and the Cancer and Leukemia Group B (CALGB) have shown an increase in bone mineral density in premenopausal women. BPs as anticancer treatment are, however, still controversial because several studies yielded conflicting results, with beneficial effects only in subgroups of patients. The publication of the latest Oxford overview of prospective trials is being awaited; at the presentation of the results, a 34% relative reduction of bone metastasis and a 17% improvement in overall survival was demonstrated in the subgroup of postmenopausal patients. These results will likely lead to an incorporation of the use of BPs into routine adjuvant breast cancer treatment.

Osteoporose bei hormonablativer Therapie

“…Aus osteoonkologisch adjuvanter Sicht ist eine antiresorptive Therapie in mehrerer Hinsicht zu einem früheren Zeitpunkt als bisher bei dem AI bedingten postmenopausalen Knochenmasseverlust essenziell: Daten zum krankheitsfreien Überleben und Daten zu Antitumoreffekten der adjuvanten Therapie mit Bisphosphonaten (für Denosumab mit aktuell laufenden Studien zur Erweiterung der Evidenz) belegen dies. In der Situation der adjuvanten Behandlung wurde unter Bisphosphonat-Therapie neben einem Anstieg der Knochendichte in einer Subgruppe von postmenopausalen Frauen eine 34-%ige relative Reduktion von Knochenmetastasen und eine 17-%ige Verbesserung im Überleben gesehen (25). Dies wird in naher Zukunft zu einer Änderung der Therapieempfehlungen bei Frauen unter antihormoneller Therapie führen, bisher bezieht sich aber auch die S3-Leitlinie "Supportive Therapie bei onkologischen Patienten" (AWMF-Registernummer: 032/0540L) in den Diagnostik-und Therapieempfehlungen auf die in der osteologischen Leitlinie ausgesprochenen.…”

Postmenopausal Breast Cancer, Aromatase Inhibitors, and Bone Health: What the Surgeon Should Know

“…Intravenous bisphosphonate therapy such as Zoledronic Acid is currently regarded the gold standard [52]. Oral bisphosphonates and Denosumab are other potential and very useful treatment options.…”

“…Fig.1Recommended algorithm for bone protection in postmenopausal breast cancer patients, on aromatase inhibitors (AI). Adopted with permission of Hadji et al[41,52] …”