Single-nucleotide polymorphism biomarkers of adjuvant anastrozole-induced estrogen suppression in early breast cancer.

OBJECTIVES: Based on our previous findings that postmenopausal women with estrone (E1) and estradiol (E2) concentrations at or above 1.3 pg/ml and 0.5 pg/ml, respectively, after 6 months of adjuvant anastrozole therapy had a three-fold risk of recurrence, we aimed to identify a single-nucleotide polymorphism (SNP)-based model that would predict elevated E1 and E2 and then validate it in an independent dataset. PATIENTS AND METHODS: The test set consisted of 322 women from the M3 study and the validation set consisted of 152 patients from MA.27. All patients were treated with adjuvant anastrozole, had on-anastrozole E1 and E2 concentrations and genome-wide genotyping. RESULTS: SNPs were identified from the M3 genome-wide association study. The best model to predict the E1-E2 phenotype with high balanced accuracy was a support vector machine model using clinical factors plus 46 SNPs. We did not have an independent cohort that is similar to the M3 study with clinical, E1-E2 phenotypes and genotype data to test our model. Hence, we chose a nested matched case-control cohort (MA.27 study) for testing. Our E1-E2 model was not validated but we found the MA.27 validation cohort was both clinically and genomically different. CONCLUSIONS: We identified a SNP-based model that had excellent performance characteristics for predicting the phenotype of elevated E1 and E2 in women treated with anastrozole. This model was not validated in an independent dataset but that dataset was clinically and genomically substantially different. The model will need validation in a prospective study.

Evaluation of vertebroplasty with a validated outcome measure: the Roland-Morris Disability Questionnaire.

BACKGROUND AND PURPOSE: Vertebroplasty is rapidly disseminating as a treatment for vertebral compression fractures, but its efficacy has not been assessed with a well-validated, back pain-specific instrument. We report the use of the Roland-Morris Disability Questionnaire (RDQ) in patients undergoing vertebroplasty for painful osteoporotic compression fractures. METHODS: Retrospective review of patients treated with vertebroplasty who completed the RDQ and 2 verbal pain scales (0-10) for pain at rest and pain with activity at baseline, 1 week, 1 month, 6 months, and 1 year post-vertebroplasty. Changes in outcome measures were analyzed by using a paired t test and correlations were assessed with Spearman rho. Multiple linear regression was used to analyze the relationship between baseline scores and independent variables. RESULTS: One hundred thirteen patients were treated at 164 vertebral levels. At baseline, RDQ scores were associated with rest and activity pain (P < .001 and P = .002, respectively) but were not associated with other independent variables. All 3 outcome scores decreased by 1 week and remained improved through maximal follow-up (P < .001). RDQ scores improved by a mean of 7.0 points at 1 week and remained improved at 1 year (P = .02). RDQ scores correlated with both rest and activity pain, but the absolute correlation was slightly better (+0.15 on average) with activity pain. CONCLUSIONS: Patients who underwent vertebroplasty experienced relief of back pain and symptoms, as shown by improvement in verbal pain and RDQ scores. The RDQ correlates well with measures of pain, shows clinically significant improvement and is responsive to changes across time. More important, the RDQ provides an easily administered, well-validated, back pain-specific outcome measure that could be adopted to assess vertebroplasty outcomes.