Targeted and Osteo-Oncologic Treatment in Early Breast Cancer: What Is State-of-the-Art and What Might Become so within the Next 5 Years?

Abstract

In 2014, modern strategies of targeted therapies in the adjuvant setting are mainly focused on anti-human epidermal growth factor receptor 2 (HER2) blockade. For the 15% of HER2-enriched tumors, 1 year of treatment with the monoclonal antibody trastuzumab is the standard of care. All patients, regardless of tumor size, nodal status, or age, profit from therapy with risk reduction rates for recurrence of up to 50%. As a consequence, the current guidelines recommend the use of trastuzumab in these patients if additional risk factors lead to the consideration of adjuvant chemotherapy. The concurrent use with taxane-based chemotherapy is preferred. The concept of dual HER2 blockade - already approved in the metastatic setting - shows also significantly improved efficacy in neoadjuvant trials. Dual blockade with trastuzumab and pertuzumab is approved by the Food and Drug Administration (FDA) for neoadjuvant treatment of HER2-overexpressing tumors. However, until approved in Europe, this treatment approach remains off-label for early breast cancer and study participation is highly recommended. Bisphosphonates (BPs) and denosumab are approved in breast cancer as standard therapy for the treatment of bone metastases. In the adjuvant setting, BPs and denosumab can be given to prevent tumor therapy-induced bone loss. The antineoplastic effect of BPs in the adjuvant setting and its role in the prevention of metastatic disease are still under discussion.

Tumor-Stroma Crosstalk in Bone Tissue: The Osteoclastogenic Potential of a Breast Cancer Cell Line in a Co-Culture System and the Role of EGFR Inhibition

“…Bone metastases are a common event in breast cancer (BC) patients [ 1 ], often leading to severe symptoms such as pain, bone fractures, spinal cord compression and hypercalcemia [ 2 ]. The mechanisms underlying BC-derived bone metastases have been intensively investigated but the complex interactions involved have hindered both the development of comprehensive in vitro systems [ 3 ] and the generation of translational benefits [ 4 , 5 ].…”

Management of bone health in solid tumours: From bisphosphonates to a monoclonal antibody

“…3). As noted earlier, the optimal duration of therapy remains unclear [12,79,143]. Extended dosing intervals or intermittent therapy may be used in practice, and the published data comparing different ZA dosing schedules are described above [74][75][76].…”

A Nitrobenzoyl Sesquiterpenoid Insulicolide A Prevents Osteoclast Formation via Suppressing c-Fos-NFATc1 Signaling Pathway

“…However, hyperactivity of osteoclast can lead to bone osteoclastic diseases such as osteoporosis, rheumatoid arthritis (RA), and tumor bone metastases ( Perpetuo et al, 2017 ; Tsukasaki and Takayanagi, 2019 ; Győri and Mócsai, 2020 ; Kim et al, 2020 ; Liu et al, 2021 ). Therefore, targeting osteoclast formation has been regarded as a practicable treatment strategy to improve the prognosis of patients with bone destructive diseases ( Broadhead et al, 2011 ; Stickeler and Fehm, 2014 ).…”