Assessing fracture risk in early stage breast cancer patients treated with aromatase-inhibitors: An enhanced screening approach incorporating trabecular bone score

AbstractIntroductionAromatase-inhibitors (AIs) are commonly used for treatment of patients with hormone-receptor positive breast carcinoma, and are known to induce bone density loss and increase the risk of fractures. The current standard-of-care screening tool for fracture risk is bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA). The fracture risk assessment tool (FRAX®) may be used in conjunction with BMD to identify additional osteopenic patients at risk of fracture who may benefit from a bone-modifying agent (BMA). The trabecular bone score (TBS), a novel method of measuring bone microarchitecture by DXA, has been shown to be an independent indicator of increased fracture risk. We report how the addition of TBS and FRAX®, respectively, to BMD contribute to identification of elevated fracture risk (EFR) in postmenopausal breast cancer patients treated with AIs.Methods100 patients with early stage hormone-positive breast cancer treated with AIs, no prior BMAs, and with serial DXAs were identified. BMD and TBS were measured from DXA images before and following initiation of AIs, and FRAX® scores were calculated from review of clinical records. EFR was defined as either: BMD ≤−2.5 or BMD between −2.5 and −1 plus either increased risk by FRAX® or degraded microstructure by TBS.ResultsAt baseline, BMD alone identified 4% of patients with EFR. The addition of FRAX® increased detection to 13%, whereas the combination of BMD, FRAX® and TBS identified 20% of patients with EFR. Following AIs, changes in TBS were independent of changes in BMD. On follow-up DXA, BMD alone detected an additional 1 patient at EFR (1%), whereas BMD+ FRAX® identified 3 additional patients (3%), and BMD+FRAX®+TBS identified 7 additional patients (7%).ConclusionsThe combination of FRAX®, TBS, and BMD maximized the identification of patients with EFR. TBS is a novel assessment that enhances the detection of patients who may benefit from BMAs

Osteonecrosis of the Maxilla and Mandible in Patients with Advanced Cancer Treated with Bisphosphonate Therapy

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/139939/1/onco0911.pd

Refractory hypercalcemia of malignancy: a problem with many potential roots

Hypercalcemia of malignancy (HCM) is a common clinical problem that is associated with considerable morbidity and negative effects on quality of life. Despite the availability of effective medical treatments for HCM, options are needed for cases that are refractory to conventional therapies. In this context, “refractory” refers to reasonable control of calcium in the setting of inpatient hospitalization (after receipt of standard of care therapies, such as continuous intravenous fluids, calcitonin, and intravenous bisphosphonates) with relapse into severe hypercalcemia within days or weeks of discharge from the hospital. Here we discuss drivers of hypercalcemia of malignancy and the physiologic mechanisms whereby they operate to increase serum calcium. Additionally, we discuss multiple available treatments targeted to a given contributory mechanism and also briefly discuss potential future treatments in need of further study

Pituitary as a Source of HCG: Residual Levels After Bilateral Testicular Tumor Removal

Context . Challenging clinical scenario in which elevated β-human chorionic gonadotropin (HCG, subsequently termed HCG) levels suggested occult tumor metastases after removal of bilateral testicular cancers and metastases from them and as well as after chemotherapy. Case Report . A 22-year-old male, post excision of bilateral testicular tumors, who had no imaging or clinical evidence of residual tumor but an elevated HCG raising the question of the presence and location of occult tumor metastases. Clinical Questions . Does luteinizing hormone (LH) cross-react with HCG in current assays? What levels of testosterone and estradiol are necessary to suppress LH and follicle-stimulating hormone (FSH) in a male patient with bilateral orchiectomy, and therefore lacking inhibin? Does the pituitary secrete HCG and under what circumstances? Assessment . Current HCG assays no longer cross-react with LH as did prior assays, but the presence of heterophile antibodies and other factors such as biotin can still cause false positive HCG levels. In the chronic post-orchiectomy state, the pituitary is relatively resistant to LH and FSH suppression by testosterone. The pituitary secretes HCG in very small amounts unless interruption of negative feedback results in high LH and FSH whereupon HCG levels become elevated. Clinical Conclusion . A GnRH antagonist suppressed both LH and HCG in this patient indicating that the elevated HCG was secreted by the pituitary and not by occult tumor metastases. Further credence for this conclusion resulted from the lack of a progressive increase in HCG levels over a 4-year period of follow-up and from no evidence of metastatic tumors on serial imaging

Pituitary as a Source of HCG: Residual Levels After Bilateral Testicular Tumor Removal

Context . Challenging clinical scenario in which elevated β-human chorionic gonadotropin (HCG, subsequently termed HCG) levels suggested occult tumor metastases after removal of bilateral testicular cancers and metastases from them and as well as after chemotherapy. Case Report . A 22-year-old male, post excision of bilateral testicular tumors, who had no imaging or clinical evidence of residual tumor but an elevated HCG raising the question of the presence and location of occult tumor metastases. Clinical Questions . Does luteinizing hormone (LH) cross-react with HCG in current assays? What levels of testosterone and estradiol are necessary to suppress LH and follicle-stimulating hormone (FSH) in a male patient with bilateral orchiectomy, and therefore lacking inhibin? Does the pituitary secrete HCG and under what circumstances? Assessment . Current HCG assays no longer cross-react with LH as did prior assays, but the presence of heterophile antibodies and other factors such as biotin can still cause false positive HCG levels. In the chronic post-orchiectomy state, the pituitary is relatively resistant to LH and FSH suppression by testosterone. The pituitary secretes HCG in very small amounts unless interruption of negative feedback results in high LH and FSH whereupon HCG levels become elevated. Clinical Conclusion . A GnRH antagonist suppressed both LH and HCG in this patient indicating that the elevated HCG was secreted by the pituitary and not by occult tumor metastases. Further credence for this conclusion resulted from the lack of a progressive increase in HCG levels over a 4-year period of follow-up and from no evidence of metastatic tumors on serial imaging