Medication-Related Osteonecrosis of the Jaw with the mTOR Inhibitor Everolimus in a Patient with Estrogen-Receptor Positive Breast Cancer: A Case Report

Abstract

with breast cancer under the age of 50-years (approximately 49,000 women) and is a leading cause of death in this age group [1]. It is estimated that over 40,000 women will die of this disease in 2015 [2]. More than 50% have estrogen-receptor positive (ER+) disease, although estrogen is a steroid sex hormone required for normal breast development [3]. There is a strong correlation between exposure to estrogen and development of breast cancer [3,4]. Breast cancer due to elevated blood levels of estrogen is the most frequent type of invasive malignancy that affects over 1 million women worldwide [4]. Breast carcinogenesis is due to metabolism of estrogen to genotoxic metabolites and cellular growth and proliferation that leads to initiation, promotion and development of breast cancer [5].

Cancer Patients at Risk for Medication-Related Osteonecrosis of the Jaw. A Case and Control Study Analyzing Predictors of MRONJ Onset

“…It is known, for example, that the combination of anti-VEGFR and bone antiresorptive agents may increase the risk of MRONJ [ 60 , 61 , 62 ]. Similarly, it was well confirmed that mTOR inhibitors have a strong immunosuppressive effect, which can lead to delayed healing of oral soft tissues and persistent infections favoring the onset of the osteonecrotic process [ 63 , 64 ]. Taking into account these observations and their potential etiologies, the following hypothesis has been developed for MRONJ onset: (1) a direct local effect represented by the epithelial damage [ 65 , 66 , 67 , 68 , 69 ]; (2) an indirect systemic effect exerted by the immunosuppressive action of anti-cancer treatments [ 70 , 71 ], since the new concept of osteoimmunology [ 72 ] was recently added to the previous etiopathogenetic theories on MRONJ development [ 73 ]; and lastly, (3) the hypothesis that new anticancer drugs may play a role in osteoclast differentiation by additionally affecting the RANKL-mediated cell cycle arrest, as supported by recent in vitro and in vivo data [ 74 , 75 ].…”