Implementation of Breast Cancer Risk Assessment Tool using SAS ® Yuqin Li, inVentiv Health Clinical, Indianapolis, IN

ABSTRACT In this paper, a SAS macro is developed to implement the breast cancer risk assessment (BCRA) tool designed by National Cancer Institute (NCI). The BCRA tool itself is based on a complex statistical model known as the Gail model. The Gail model provides an estimate of a woman's risk of developing invasive breast cancer over a specific period of time by utilizing an individual's demographic information and risk factors. Breast cancer risk factors considered in the Gail model include (1) the number of previous breast biopsies, (2) the presence of atypical hyperplasia in any previous breast biopsy specimen, (3) age at the start of menstruation, (4) age at the first live birth of a child, (5) the history of breast cancer among her first-degree relatives (mother, sisters, daughters), and (6) the individual's age and race. The statistical model calculates individualized invasive breast cancer risk in terms of probabilities based on both the relative risk and the baseline hazard rate. We converted the C++ source code available from the NCI website to a SAS© macro. Features of the macro include ease of implementation and integration through SAS© as well as flexibility in calculating the probabilistic breast cancer risk at any duration of time

Changes observed in radionuclide bone scans during and after teriparatide treatment for osteoporosis

# The Author(s) 2011. This article is published with open access at Springerlink.com Purpose Visual changes on radionuclide bone scans have been reported with teriparatide treatment. To assess this, serial studies were evaluated and quantified in ten postmenopausal women with osteoporosis treated with teriparatide (20 μg/day subcutaneous) who had 99m Tc-methylene diphosphonate (MDP) bone scans (baseline, 3 and 18 months, then after 6 months off therapy). Methods Women were injected with 600 MBq 99m Tc-MDP, and diagnostic bone scan images were assessed at 3.5 h. Additional whole-body scans (10 min, 1, 2, 3 and 4 h) were analysed for 99m Tc-MDP skeletal plasma clearance (Kbone). Regional Kbone differences were obtained for the whole skeleton and six regions (calvarium, mandible, spine, pelvis, upper and lower extremities). Bone turnover markers (BTM) were also measured. Results Most subjects showed visual changes on 3- and 18month bone scan images that disappeared after 6 months off therapy. Enhanced uptake was seen predominantly in the calvarium and lower extremities. Whole skeleton Kbone displayed a median increase of 22 % (3 months, p=0.004) and 34 % (18 months, p=0.002) decreasing to 0.7% (6 months off therapy). Calvarium Kbone changes were three times larger than other sites. After 6 months off therapy, all Kbone and BTM values returned towards baseline

Role of Heat Treatment on Atomic Order and Ordering Domains in Ni45Co5Mn36.6In13.4 Ribbons

The effects of cooling rate and annealed temperature on the state of atomic order and microstructure of L21 domains of Ni45Co5Mn36.6In13.4 ribbons are investigated comprehensively. The state of atomic order is quantitatively studied by in situ X-ray diffraction (XRD), and the microstructure of ordered domains is revealed by transmission electron microscopy (TEM). As-spun ribbons show B2 structure of low atomic order, exhibiting the dispersive L21 domains’ morphology. By applying heat treatment around the order–disorder transition temperature followed by furnace cooling or quenching into water, respectively, we found the strong dependence of ordered domains on cooling rates. Furnace cooling samples show L21 domains with small sized antiphase boundary, revealing a high degree of atomic order, while quenching hinders the formation of ordered domains. Annealing above the order–disorder transition temperature followed by quenching preserves the disordered atomic state with the mixture of L21 structure in B2 matrix

Effects of low-dose estrogen replacement during childhood on pubertal development and gonadotropin concentrations in patients with Turner syndrome: results of a randomized, double-blind, placebo-controlled clinical trial

CONTEXT: The optimal approach to estrogen replacement in girls with Turner syndrome has not been determined. OBJECTIVE: The aim of the study was to assess the effects of an individualized regimen of low-dose ethinyl estradiol (EE2) during childhood from as early as age 5, followed by a pubertal induction regimen starting after age 12 and escalating to full replacement over 4 years. DESIGN: This study was a prospective, randomized, double-blind, placebo-controlled clinical trial. SETTING: The study was conducted at two US pediatric endocrine centers. SUBJECTS: Girls with Turner syndrome (n = 149), aged 5.0-12.5 years, were enrolled; data from 123 girls were analyzable for pubertal onset. INTERVENTION(S): Interventions comprised placebo or recombinant GH injections three times a week, with daily oral placebo or oral EE2 during childhood (25 ng/kg/d, ages 5-8 y; 50 ng/kg/d, ages >8-12 y); after age 12, all patients received escalating EE2 starting at a nominal dosage of 100 ng/kg/d. Placebo/EE2 dosages were reduced by 50% for breast development before age 12 years, vaginal bleeding before age 14 years, or undue advance in bone age. MAIN OUTCOME MEASURES: The main outcome measures for this report were median ages at Tanner breast stage ≥2, median age at menarche, and tempo of puberty (Tanner 2 to menarche). Patterns of gonadotropin secretion and impact of childhood EE2 on gonadotropins also were assessed. RESULTS: Compared with recipients of oral placebo (n = 62), girls who received childhood low-dose EE2 (n = 61) had significantly earlier thelarche (median, 11.6 vs 12.6 y, P < 0.001) and slower tempo of puberty (median, 3.3 vs 2.2 y, P = 0.003); both groups had delayed menarche (median, 15.0 y). Among childhood placebo recipients, girls who had spontaneous breast development before estrogen exposure had significantly lower median FSH values than girls who did not. CONCLUSIONS: In addition to previously reported effects on cognitive measures and GH-mediated height gain, childhood estrogen replacement significantly normalized the onset and tempo of puberty. Childhood low-dose estrogen replacement should be considered for girls with Turner syndrome

Femoral strength in osteoporotic women treated with teriparatide or alendronate

To gain insight into the clinical effect of teriparatide and alendronate on the hip, we performed non-linear finite element analysis of quantitative computed tomography (QCT) scans from 48 women who had participated in a randomized, double-blind clinical trial comparing the effects of 18-month treatment of teriparatide 20 μg/d or alendronate 10 mg/d. The QCT scans, obtained at baseline, 6, and 18 months, were analyzed for volumetric bone mineral density (BMD) of trabecular bone, the peripheral bone (defined as all the cortical bone plus any endosteal trabecular bone within 3 mm of the periosteal surface), and the integral bone (both trabecular and peripheral), and for overall femoral strength in response to a simulated sideways fall. At 18 months, we found in the women treated with teriparatide that trabecular volumetric BMD increased versus baseline (+ 4.6%, p < 0.001), peripheral volumetric BMD decreased (− 1.1%, p < 0.05), integral volumetric BMD (+ 1.0%, p = 0.38) and femoral strength (+ 5.4%, p = 0.06) did not change significantly, but the ratio of strength to integral volumetric BMD ratio increased (+ 4.0%, p = 0.04). An increase in the ratio of strength to integral volumetric BMD indicates that overall femoral strength, compared to baseline, increased more than did integral density. For the women treated with alendronate, there were small ( < 1.0%) but non-significant changes compared to baseline in all these parameters. The only significant between-treatment difference was in the change in trabecular volumetric BMD (p < 0.005); related, we also found that, for a given change in peripheral volumetric BMD, femoral strength increased more for teriparatide than for alendronate (p = 0.02). We conclude that, despite different compartmental volumetric BMD responses for these two treatments, we could not detect any overall difference in change in femoral strength between the two treatments, although femoral strength increased more than integral volumetric BMD after treatment with teriparatide

Assessing the Effects of Teriparatide Treatment on Bone Mineral Density, Bone Microarchitecture, and Bone Strength

BackgroundTo gain insight into how teriparatide affects various bone health parameters, we assessed the effects of teriparatide treatment with use of standard DXA (dual x-ray absorptiometry) technology and two newer technologies, high-resolution MRI (magnetic resonance imaging) and finite element analysis of quantitative CT (computed tomography) scans.MethodsIn this phase-4, open-label study, postmenopausal women with severe osteoporosis received 20 μg/day of teriparatide. Assessments included (1) changes in areal BMD (bone mineral density) (in g/cm2) at the radius, spine, and hip on DXA, (2) changes in volumetric BMD (in mg/cm3) at the spine and hip on quantitative CT scans, (3) changes in bone microarchitecture at the radius on high-resolution MRI, (4) estimated changes in spine and hip strength according to finite element analysis of quantitative CT scans, (5) changes in bone turnover markers in serum, and (6) safety.ResultsThirty-five subjects were enrolled; thirty completed eighteen months and twenty-five completed an optional six-month extension. No significant changes were observed for the primary outcome, high-resolution MRI at the distal aspect of the radius. At month eighteen, the least-squares mean percentage change from baseline in total volumetric BMD at the spine was 10.05% (95% confidence interval [CI], 6.83% to 13.26%; p &lt; 0.001), and estimated spine strength increased 17.43% (95% CI, 12.09% to 22.76%; p &lt; 0.001). Total volumetric BMD at the hip increased 2.22% (95% CI, 0.37% to 4.06%; p = 0.021), and estimated hip strength increased 2.54% (95% CI, 0.06% to 5.01%; p = 0.045). Areal BMD increased at the lumbar spine and femoral neck, was unchanged for the total hip and at the distalmost aspect of the radius, and decreased at a point one-third of the distance between the wrist and elbow. Bone turnover markers increased at months three, six, and twenty-four (all p &lt; 0.05). No unexpected adverse events were observed.ConclusionsHigh-resolution MRI failed to identify changes in bone microarchitecture at the distal aspect of the radius, a non-weight-bearing site that may not be suitable for assessing effects of an osteoanabolic agent. Teriparatide increased areal BMD at the spine and femoral neck and volumetric BMD at the spine and hip. Estimated vertebral and femoral strength also increased. These findings and increases in bone turnover markers through month twenty-four are consistent with the known osteoanabolic effect of teriparatide.Level of evidenceTherapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence