A Review of Literature on Updates of Bisphosphonates Administration, Cancer Biomarkers for Bisphosphonate Therapy, and Bisphosphonate-related Osteonecrosis of the Jaw in Breast Cancer

Abstract

Context: The emergence of bone health maintenance in breast cancer patients is known as an indispensable aspect in survival and morbidity improvement; therefore, bisphosphonates play a substantial role in the prevention/delaying of cancer treatment induced bone loss and skeletal-related events (SREs) in these patients, although this drug can cause necrosis of the jaw. In this article, we aimed at summarizing updated evidence on bisphosphonates administration, biomarkers representative of the efficacy of bisphosphonate therapy, and bisphosphonate-related osteonecrosis of the jaw (BRONJ) affection in patients involved in breast cancer. Methods: Associated published articles were searched for in EMBASE, MEDLINE, CDSR, PubMed, Google Scholar, and CINAHL, using the following keywords or, in the case of PubMed database, medical subject headings (MeSH): ‘Diphosphonate’, ‘osteonecrosis’, ‘breast cancer’, and ‘biomarker’ in the abstract or title, and was limited by "clinical trials, meta-analysis and randomized controlled trial” published in English language from 2015 to 2020-09-15. Results: Bisphosphonates depicted remarkable advantages in improving SREs, skeletal morbidity rate (SMR), survival rate, and treatment-emergent adverse events in breast cancer patients in almost all aspects of breast cancer therapy, from adjuvant therapy for the early stage breast cancer to bone metastatic breast cancer (BMBC). The identification of breast cancer biomarkers that are capable of reflecting the outcomes of bisphosphonates therapy is a highly advantageous aid in the optimal utilization of these drugs. Breast cancer biomarkers such as MAF, DOCK4, CD73, TLR9, and CAPG/GIPC1 composite illustrated a significant correlation with bisphosphonates administration. Medication-related osteonecrosis of the jaw (MRONJ) stands out as the most hazardous adverse event of the bisphosphonates with a rationally high incidence among breast cancer patients, which requires cautious prescription of bisphosphonates as well as regular dental health counseling for being prevented. Conclusions: Bisphosphonates are great weapons in the arsenal of breast cancer treatment and, therefore, comprehensive studying of their features leads to the optimal and safe administration of them. Unfortunately, as this procedure can cause necrosis of the jaw, dental procedures should be performed in these patients before starting bisphosphonate treatment.