Weight gain is a common problem among breast cancer patients who receive adjuvant chemotherapy (CT). We undertook a study to determine the causes of this energy imbalance.
Factors related to energy ...balance were assessed at baseline (within 3 weeks of diagnosis) and throughout 1 year postdiagnosis among 53 premenopausal women with operable breast carcinoma. Thirty-six patients received CT and 17 received only localized treatment (LT). Measures included body composition (dual energy x-ray absorptiometry), resting energy expenditure (REE; indirect calorimetry), dietary intake (2-day dietary recalls and food frequency questionnaires) and physical activity (physical activity records).
Mean weight gain in the LT patients was 1.0 kg versus 2.1 kg in the CT group (P =.02). No significant differences between groups in trend over time were observed for REE and energy intake; however, a significant difference was noted for physical activity (P =.01). Several differences between groups in 1-year change scores were detected. The mean change (+/- SE) in LT versus CT groups and P values for uncontrolled/controlled (age, race, radiation therapy, baseline body mass index, and end point under consideration) analysis are as follows: percentage of body fat (-0.1 +/- 0.4 v +2.2 +/- 0.6%; P =.001/0.04); fat mass (+0.1 +/- 0.3 v +2.3 +/- 0.7 kg; P =.002/0.04); lean body mass (+0.8 +/- 0.2 v -0.4 +/- 0.3 kg; P =.02/0.30); and leg lean mass (+0.5 +/- 0.1 v -0.2 +/- 0.1 kg; P =.01/0.11).
These data do not support overeating as a cause of weight gain among breast cancer patients who receive CT. The data suggest, however, that CT-induced weight gain is distinctive and indicative of sarcopenic obesity (weight gain in the presence of lean tissue loss or absence of lean tissue gain). The development of sarcopenic obesity with evidence of reduced physical activity supports the need for interventions focused on exercise, especially resistance training in the lower body, to prevent weight gain.
Using a 2 x 2 factorial design, we studied the adjuvant chemotherapy of women with axillary node-positive breast cancer to compare sequential doxorubicin (A), paclitaxel (T), and cyclophosphamide (C) ...with concurrent doxorubicin and cyclophosphamide (AC) followed by paclitaxel (T) for disease-free (DFS) and overall survival (OS); to determine whether the dose density of the agents improves DFS and OS; and to compare toxicities.
A total of 2,005 female patients were randomly assigned to receive one of the following regimens: (I) sequential A x 4 (doses) --> T x 4 --> C x 4 with doses every 3 weeks, (II) sequential A x 4 --> T x 4 --> C x 4 every 2 weeks with filgrastim, (III) concurrent AC x 4 --> T x 4 every 3 weeks, or (IV) concurrent AC x 4 --> T x 4 every 2 weeks with filgrastim.
A protocol-specified analysis was performed at a median follow-up of 36 months: 315 patients had experienced relapse or died, compared with 515 expected treatment failures. Dose-dense treatment improved the primary end point, DFS (risk ratio RR = 0.74; P =.010), and OS (RR = 0.69; P =.013). Four-year DFS was 82% for the dose-dense regimens and 75% for the others. There was no difference in either DFS or OS between the concurrent and sequential schedules. There was no interaction between density and sequence. Severe neutropenia was less frequent in patients who received the dose-dense regimens.
Dose density improves clinical outcomes significantly, despite the lower than expected number of events at this time. Sequential chemotherapy is as effective as concurrent chemotherapy.
The molecular underpinnings of HER2-low and HER2-0 (IHC 0) breast tumors remain poorly defined. Using genomic findings from 1039 patients with HER2-negative metastatic breast cancer undergoing ...next-generation sequencing from 7/2013-12/2020, we compare results between HER2-low (n = 487, 47%) and HER2-0 tumors (n = 552, 53%). A significantly higher number of ERBB2 alleles (median copy count: 2.05) are observed among HER2-low tumors compared to HER2-0 (median copy count: 1.79; P = 2.36e-6), with HER2-0 tumors harboring a higher rate of ERBB2 hemideletions (31.1% vs. 14.5%). No other genomic alteration reaches significance after accounting for multiple hypothesis testing, and no significant differences in tumor mutational burden are observed between HER2-low and HER2-0 tumors (median: 7.26 mutations/megabase vs. 7.60 mutations/megabase, p = 0.24). Here, we show that the genomic landscape of HER2-low and HER2-0 tumors does not differ significantly, apart from a higher ERBB2 copy count among HER2-low tumors, and a higher rate of ERBB2 hemideletions in HER2-0 tumors.
The gamma -ray sky can be decomposed into individually detected sources, diffuse emission attributed to the interactions of Galactic cosmic rays with gas and radiation fields, and a residual all-sky ...emission component commonly called the isotropic diffuse gamma -ray background (IGRB). The IGRB comprises all extragalactic emissions too faint or too diffuse to be resolved in a given survey, as well as any residual Galactic foregrounds that are approximately isotropic. The first IGRB measurement with the Large Area Telescope (LAT) on board the Fermi Gamma-ray Space Telescope (Fermi) used 10 months of sky-survey data and considered an energy range between 200 MeV and 100 GeV. Improvements in event selection and characterization of cosmic-ray backgrounds, better understanding of the diffuse Galactic emission (DGE), and a longer data accumulation of 50 months allow for a refinement and extension of the IGRB measurement with the LAT, now covering the energy range from 100 MeV to 820 GeV. The IGRB spectrum shows a significant high-energy cutoff feature and can be well described over nearly four decades in energy by a power law with exponential cutoff having a spectral index of 2.32 + or - 0.02 and a break energy of (279 + or - 52) GeV using our baseline DGE model. The total intensity attributed to the IGRB is (7.2 + or - 0.6) x 10 super(-6) cm super(-2) s super(-1) sr super(-1) above 100 MeV, with an additional +15%/-30% systematic uncertainty due to the Galactic diffuse foregrounds.
Online track processor for the CDF upgrade Thomson, E.J.; Ciobanu, C.; Chung, J.Y. ...
IEEE transactions on nuclear science,
06/2002, Letnik:
49, Številka:
3
Journal Article
Recenzirano
Odprti dostop
A trigger track processor, called the eXtremely Fast Tracker (XFT), has been designed for the Collider Detector at Fermilab (CDF) upgrade. This processor identifies high-transverse-momentum (> 1.5 ...GeV/c) charged particles in the new central outer tracking chamber for CDF II. The XFT design is highly parallel to handle the input rate of 183 Gb/s and the output rate of 44 Gb/s. The processor is pipelined and reports the result for a new event every 132 ns. The processor uses three stages: hit classification, segment finding, and segment linking. The pattern recognition algorithms for the three stages are implemented in programmable logic devices (PLDs) which allow in situ modification of the algorithm at any time. The PLDs reside on three different types of modules. The complete system has been installed and commissioned at CDF II. An overview of the track processor and performance in CDF Run II are presented.
In this study, women 70 years of age or older who had early, estrogen-receptor–positive breast cancer underwent lumpectomy and were then randomly assigned to receive tamoxifen alone or with local ...irradiation. The only significant difference in outcome was in the probability of local recurrence at five years (4 percent in the tamoxifen group and 1 percent in the combined-treatment group).
For women 70 years of age or older, lumpectomy plus adjuvant treatment with tamoxifen (without local irradiation) is a reasonable choice.
Multiple trials of breast-conserving surgery for breast cancer
1
–
5
have shown that postoperative irradiation decreases the rate of ipsilateral recurrence but offers no survival benefit. However, the high rate of recurrence with surgery alone (10 to 40 percent) has suggested that the only two appropriate treatments are modified radical mastectomy and breast-conserving surgery plus adjuvant radiation therapy. Since tamoxifen, with
3
or without
4
radiation therapy, decreases the risk of recurrence, and given the cost and adverse effects of breast irradiation
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–
12
and its negative effect on the quality of life,
6
,
7
we designed a trial to determine whether women 70 years . . .
The Fermi bubbles are two large structures in the gamma-ray sky extending to 55degrees above and below the Galactic center. We analyze 50 months of Fermi Large Area Telescope data between 100 MeV and ...500 GeV above 10degrees in Galactic latitude to derive the spectrum and morphology of the Fermi bubbles. We thoroughly explore the systematic uncertainties that arise when modeling the Galactic diffuse emission through two separate approaches. The gamma-ray spectrum is well described by either a log parabola or a power law with an exponential cutoff. We exclude a simple power law with more than 7sigma significance. The power law with an exponential cutoff has an index of 1.9 + or - 0.2 and a cutoff energy of 110 + or - 50 GeV. We find that the gamma-ray luminosity of the bubbles is (ProQuest: Formulae and/or non-USASCII text omitted)erg s super(-1). We confirm a significant enhancement of gamma-ray emission in the southeastern part of the bubbles, but we do not find significant evidence for a jet. No significant variation of the spectrum across the bubbles is detected. The width of the boundary of the bubbles is estimated to be (ProQuest: Formulae and/or non-USASCII text omitted) deg. Both inverse Compton (IC) models and hadronic models including IC emission from secondary leptons fit the gamma-ray data well. In the IC scenario, synchrotron emission from the same population of electrons can also explain the WMAP and Planck microwave haze with a magnetic field between 5 and 20 mu G.
Trastuzumab combined with chemotherapy improves outcomes for women with human epidermal growth factor receptor 2 (HER2) overexpressing advanced breast cancer. We conducted a pilot study of ...preoperative trastuzumab and paclitaxel, followed by surgery and adjuvant doxorubicin and cyclophosphamide chemotherapy in earlier stage breast cancer.
Patients with HER2-positive (2+ or 3+ by immunohistochemistry) stage II or III breast cancer received preoperative trastuzumab (4 mg/kg x 1, then 2 mg/kg/wk x 11) in combination with paclitaxel (175 mg/m(2) every 3 weeks x 4). Patients received adjuvant doxorubicin and cyclophosphamide chemotherapy following definitive breast surgery. Clinical and pathologic response rates were determined after preoperative therapy. Left ventricular ejection fraction and circulating levels of HER2 extracellular domain were measured serially.
Preoperative trastuzumab and paclitaxel achieved clinical response in 75% and complete pathologic response in 18% of the 40 women on study. HER2 3+ tumors were more likely to respond than 2+ tumors (84% v 38%). No unexpected treatment-related noncardiac toxicity was encountered. Four patients developed grade 2 cardiotoxicity (asymptomatic declines in left ventricular ejection fraction). Baseline HER2 extracellular domain was elevated in 24% of patients and declined with preoperative therapy. Immunohistochemical analyses of posttherapy tumor specimens indicated varying patterns of HER2 expression following trastuzumab-based treatment.
Preoperative trastuzumab and paclitaxel is active against HER2 overexpressing early-stage breast cancer and may be feasible as part of a sequential treatment program including anthracyclines. The observed changes in cardiac function merit further investigation. Correlative analyses of HER2 status may facilitate understanding of tumor response and resistance to targeted therapy.
Background
Neoadjuvant chemotherapy is being increasingly used in operable breast cancer. There are limited data on the safety of bevacizumab (bev) in the neoadjuvant setting. We sought to explore ...the safety of neoadjuvant cisplatin/bev in a protocol for triple negative breast cancer (TNBC).
Materials and Methods
A total of 51 patients with confirmed TNBC were enrolled in a single-arm trial of neoadjuvant cisplatin plus bev. Of the 51 patients, 28 with confirmed TNBC were enrolled in our trial of single-agent neoadjuvant cisplatin. Two-sided Fisher exact test were used for comparing the 2 trials.
Results
The 51 patients received neoadjuvant protocol therapy with cisplatin/bev and underwent definitive local therapy. Breast conserving therapy (BCT) was performed in 29 (57%) and mastectomy with or without reconstruction in 22 (43%). Postoperative complications were reported in 22 patients (43%); 4 (8%) required explanation of expanders. Also, 28 patients completed neoadjuvant cisplatin therapy. BCT was performed in 13 (46%) and mastectomy with or without reconstruction in 15 (54%). Postoperative complications were reported in 11 patients (39%). None of the 5 reconstructions were lost. We compared all toxicities between the two trials (
P
= .81 NS), and wound healing related complications between the two trials (
P
= .10 NS).
Conclusions
Cisplatin/bevacizumab and cisplatin alone neoadjuvant therapy resulted in a significant number of postoperative complications. Specifically, use of expanders/implants may be problematic for patients treated with bev. However, this was a single-arm trial; randomized controlled studies will be needed to determine the optimal use of bevacizumab in the timing of breast cancer surgery.
We present a catalog of gamma-ray sources at energies above 10 GeV based on data from the Large Area Telescope (LAT) accumulated during the first 3 yr of the Fermi Gamma-ray Space Telescope mission. ...The first Fermi-LAT catalog of >10 GeV sources (1FHL) has 514 sources. For each source we present location, spectrum, a measure of variability, and associations with cataloged sources at other wavelengths. We found that 449 (87%) could be associated with known sources, of which 393 (76% of the 1FHL sources) are active galactic nuclei. Of the 27 sources associated with known pulsars, we find 20 (12) to have significant pulsations in the range >10 GeV (>25 GeV). In this work we also report that, at energies above 10 GeV, unresolved sources account for 27% +/- 8% of the isotropic γ -ray background, while the unresolved Galactic population contributes only at the few percent level to the Galactic diffuse background. We also highlight the subset of the 1FHL sources that are best candidates for detection at energies above 50-100 GeV with current and future ground-based γ -ray observatories.
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