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The incidence of bone metastasis after early-stage breast cancer in Canada.

Current information on the incidence and prevalence of bone metastases in women with breast cancer is scarce. This study examined the occurrence and predictors of bone metastases, as well as post-metastasis survival in a prospective cohort of Canadian women with breast cancer. We included women treated for early-stage (stage I, II, or III) breast cancer at the Henrietta Banting Breast Centre (HBBC) in Toronto, Canada between 1987 and 2000. Data were abstracted from medical records and pathology reports in the HBBC database; follow-up extended to end of data availability or August 31, 2015. Actuarial survival analyses provided cumulative incidence of bone metastases at 5, 10, and 15 years after breast cancer diagnosis. Kaplan-Meier curves describe breast cancer mortality. Regression models assessed patient, tumor, and treatment characteristics as predictors of bone metastases with all-cause mortality as a competing risk. Among 2097 women studied, the 5-, 10-, and 15-year probability of bone metastasis was 6.5, 10.3, and 11.3 % for the first recurrence, and 8.4, 12.5, and 13.6 % for any bone recurrence. At median follow-up (12.5 years), 13.2 % of patients had bone metastases. Median survival was 1.6 years following bone metastasis, and shorter if both bone and visceral metastases occurred. Advanced age and adjuvant treatment with tamoxifen were protective against bone metastasis. In this representative cohort of women diagnosed with early-stage breast cancer in Ontario, Canada, with long follow-up, the incidence of bone metastases was consistent with longitudinal studies from the United Kingdom, Denmark, and the US.

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Economic Burden of Switching to a Non-Tumor Necrosis Factor Inhibitor Versus a Tumor Necrosis Factor Inhibitor Biologic Therapy among Patients with Rheumatoid Arthritis.

The objective of this study was to examine healthcare resource utilization (HRU) and costs associated with switching to another tumor necrosis factor alpha inhibitor (TNFi) therapy versus a non-TNFi therapy among patients with rheumatoid arthritis (RA) discontinuing use of an initial TNFi biologic therapy.
Patients with ≥2 RA diagnoses who used ≥1 TNFi on or after their initial RA diagnosis were identified in a US employer-based insurance claims database. Patients were selected based on ≥1 claim of another TNFi or a non-TNFi biologic therapy (occurring after 2010, and within 30 days before to 60 days after discontinuation of the initial TNFi), and continuous insurance ≥6 months before (baseline period) and ≥12 months after the switch date (study period). Patient demographic and clinical characteristics were measured during the baseline period. All-cause and RA-related HRU and costs were analyzed during the 12-month study period using multivariable regression analysis controlling for baseline characteristics and selected comorbidities.
Of the 1577 patients with RA that switched therapies, 1169 patients used another TNFi and 408 patients used a non-TNFi biologic. The most commonly used initial TNFi treatments were etanercept (50%) and adalimumab (34%) among the TNFi cohort, and infliximab (39%) and etanercept (28%) among the non-TNFi cohort. The TNFi cohort had significantly fewer outpatient visits [all-cause: 23.01 vs. 29.77 visits/patient/year; adjusted incidence rate ratio (IRR) = 0.78, P &lt; 0.001; RA-related: 7.42 vs. 13.58; adjusted IRR = 0.58, P &lt; 0.001] and rheumatologist visits (all-cause: 4.01 vs. 6.81; adjusted IRR = 0.66, P &lt; 0.001; RA-related: 3.23 vs. 6.40; adjusted IRR = 0.58, P &lt; 0.001) than the non-TNFi cohort. All-cause total costs were significantly lower for patients who switched to another TNFi instead of a non-TNFi therapy ($36,932 vs. $44,566; adjusted difference = $7045, P &lt; 0.01), as were total RA-related costs ($26,973 vs. $31,735; adjusted difference = $4904, P &lt; 0.01).
Adult patients with RA discontinuing TNFi therapy who switched to an alternative TNFi incurred lower healthcare costs than patients who switched to a non-TNFi biologic.
AbbVie, Inc.

p53: out of Africa.

Somatic mutations in the tumor suppressor gene p53 occur in more than half of all human cancers. Rare germline mutations result in the Li-Fraumeni cancer family syndrome. In this issue ofGenes&amp;Development, Jennis and colleagues (pp. 918-930) use an elegant mouse model to examine the affect of a polymorphism, P47S (rs1800371), in the N terminus of p53 that is found in Africans as well as more than a million African Americans. Remarkably, the single nucleotide change causes the mice to be substantially tumor-prone compared with littermates, suggesting that this allele causes an increased risk of developing cancer. The defect in p53 function is traced to a restriction in downstream gene regulation that reduces cell death in response to stress.
© 2016 Lane; Published by Cold Spring Harbor Laboratory Press.

The modified FACS calcein AM retention assay: a high throughput flow cytometer based method to measure cytotoxicity.

Current methods to determine cellular cytotoxicity in vitro are hampered by background signals that are caused by auto-fluorescent target and effector cells and by non-specific cell death. We combined and adjusted existing cell viability assays to develop a method that allows for highly reproducible, accurate, single cell analysis by high throughput FACS, in which non-specific cell death is corrected for. In this assay the number of living, calcein AM labeled cells that are green fluorescent are quantified by adding a fixed number of unlabeled calibration beads to the analysis. Using this modified FACS calcein AM retention method, we found EC50 values to be highly reproducible and considerably lower compared to EC50 values obtained by conventional assays, displaying the high sensitivity of this assay.
Copyright © 2015. Published by Elsevier B.V.

Whole Brain Radiotherapy and RRx-001: Two Partial Responses in Radioresistant Melanoma Brain Metastases from a Phase I/II Clinical Trial: A TITE-CRM Phase I/II Clinical Trial.

Kim et al. report two patients with melanoma metastases to the brain that responded to treatment with RRx-001 and whole brain radiotherapy (WBRT) without neurologic or systemic toxicity in the context of a phase I/II clinical trial. RRx-001 is an reactive oxygen and reactive nitrogen species (ROS/RNS)-dependent systemically nontoxic hypoxic cell radiosensitizer with vascular normalizing properties under investigation in patients with various solid tumors including those with brain metastases.
Metastatic melanoma to the brain is historically associated with poor outcomes and a median survival of 4 to 5 months. WBRT is a mainstay of treatment for patients with multiple brain metastases, but no significant therapeutic advances for these patients have been described in the literature. To date, candidate radiosensitizing agents have failed to demonstrate a survival benefit in patients with brain metastases, and in particular, no agent has demonstrated improved outcome in patients with metastatic melanoma. Kim et al. report two patients with melanoma metastases to the brain that responded to treatment with novel radiosensitizing agent RRx-001 and WBRT without neurologic or systemic toxicity in the context of a phase I/II clinical trial.
Published by Elsevier Inc.