Mitogen-activated protein kinases (MAPKs) play pivotal roles in growth, development, differentiation, and apoptosis. The exact role of a given MAPK in these processes is not fully understood. This question could be addressed using active forms of these enzymes that are independent of external stimulation and upstream reg-

Homologous recombination (HR) and non-homologous end joining (NHEJ) are alternative pathways of double-strand DNA break repair. We developed a method to quantify the efficiency of DNA repair pathways in the context of cancer therapy. The Recombination Proficiency Score (RPS) utilizes the expression levels for four genes involved in DNA repair pathway preference (RIF1, PARI, RAD51, and Ku80), such that high expression of these genes yields a low RPS. Carcinoma cells with low RPS exhibit HR suppression and frequent DNA copy number alterations, which are characteristic of error-prone repair processes that arise in HR-deficient backgrounds. The RPS system was clinically validated in patients with breast or non-small cell lung carcinomas (NSCLC). Tumors with low RPS were associated with greater mutagenesis, adverse clinical features, and inferior patient survival rates, suggesting that HR suppression plays a central role in promoting the genomic instability that fuels malignant progression. This adverse prognosis associated with low RPS was diminished if NSCLC patients received adjuvant chemotherapy, suggesting that HR suppression and associated sensitivity to platinum-based drugs counteracts the adverse prognosis associated with low RPS. Therefore, RPS may predict which therapies will be effective for individual patients, thereby enabling more personalized oncology care.

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PURPOSE External-beam accelerated partial breast irradiation (APBI) is an increasingly popular technique following treatment of patients for early-stage breast cancer with conventional breast-conserving therapy. Here we present 5-year results of a prospective trial. METHODS AND MATERIALS From 10/2003 through 11/2005, 98 evaluable patients with Stage I breast cancer were enrolled on the first dose-step (32 Gy delivered in 8 twice-daily fractions) of a prospective, multi-institutional, dose-escalation clinical trial of three-dimensional conformal external-beam APBI (3D-APBI). The median age was 61 years; the median tumor size was 0.8 cm; 89% of tumors were estrogen receptor positive; 10% had a triple-negative phenotype; and 1% had a HER-2-positive subtype. Median follow-up was 71 months (range, 2–88 months; interquartile range 64–75 months). RESULTS Five patients developed IBTR, for a 5-year actuarial IBTR rate of 5% (95% confidence interval, 1–10%). Three of these occurred in patients with triple-negative disease and 2 in non-triple-negative patients, for 5-year actuarial IBTR rates of 33% (0–57%) and 2% (0–6%; p<0.0001), respectively. On multivariate analysis, triple-negative phenotype was the only predictor of IBTR, with borderline statistical significance after adjusting for tumor grade (p=0.0537). CONCLUSIONS Overall outcomes were excellent, particularly for patients with estrogen receptor positive disease. Patients in this study with triple-negative breast cancer had a significantly higher IBTR rate than patients with other receptor phenotypes when treated with 3D-APBI. Larger, prospective 3D-APBI clinical trials should continue evaluating the effect of hormone receptor phenotype on IBTR rates.

Adolescents with primary hyperparathyroidism typically have more severe disease than adults. Contrary to popular belief, most adolescents have single gland disease and not hyperplasia associated with a genetic disorder.

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