119 research outputs found
Preventative therapies for healthy women at high risk of breast cancer
No full textIvana Sestak Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Queen Mary University of London, Charterhouse Square, London, UKAbstract: Tamoxifen has been shown to reduce the risk of developing estrogen receptor (ER)-positive breast cancer by at least 50%, in both pre- and postmenopausal women. The current challenge is to find new agents with fewer side effects and to find agents that are specifically suitable for premenopausal women with ER-negative breast cancer. Other selective estrogen receptor modulators (SERMs), such as raloxifene, arzoxifene, and lasofoxifene, have been shown to reduce the incidence of breast cancer by 50%–80%. SERMs are interesting agents for the prevention of breast cancer, but longer follow-up is needed for some of them for a complete risk–benefit profile of these drugs. Aromatase inhibitors have emerged as new drugs in the prevention setting for postmenopausal women. In the Mammary Prevention 3 (MAP3) trial, a 65% reduction in invasive breast cancer with exemestane was observed, and the Breast Cancer Intervention Study-II trial, which compared anastrozole with placebo, reported a 60% reduction in those cancers. Although SERMs and aromatase inhibitors have been proven to be excellent agents in the preventive setting specifically for postmenopausal women and ER-positive breast cancer, newer agents have to be found specifically for ER-negative breast cancers, which mostly occur in premenopausal women. Keywords: breast cancer, preventive therapy, selective estrogen receptor modulators, aromatase inhibitors, high-risk wome
Factors Predicting Late Recurrence for Estrogen Receptor-Positive Breast Cancer
No full textThis is a pre-copy-editing, author-produced PDF of an article accepted for publication in JNCI: Journal of the National Cancer Institute following peer review. The definitive publisher-authenticated version of 'Sestak, Ivana, et al. "Factors Predicting late recurrence for estrogen receptor–Positive Breast cancer." Journal of the National Cancer Institute (2013): djt244' is available online at: http://dx.doi.org/10.1093/jnci/djt24
Risk stratification in early breast cancer in premenopausal and postmenopausal women: integrating genomic assays with clinicopathological features.
No full textPURPOSE OF REVIEW: There is growing consensus that genomic assays provide useful complementary information to clinicopathological features in oestrogen receptor-positive breast cancers. Here, ongoing research with multigene tests used for postmenopausal breast cancer and new emerging prognostic and predictive markers for pre and postmenopausal women are summarised. RECENT FINDINGS: Results of the TAILORx trial have shown that women with an intermediate risk score do not benefit from adjuvant chemotherapy. Prosgina has been further investigated in a contemporary patient population in postmenopausal women and its use has been extended for premenopausal women. The EndoPredict was extensively used in decision-impact studies showing that its use can potentially reduce the need for adjuvant chemotherapy. Several new genomic assays have been developed, with some of them showing promising use for women with early oestrogen receptor-positive breast cancer. SUMMARY: New areas of research for prediction of recurrence and risk stratification involve the development of immune gene signatures that carry modest but significant prognostic value. The recent expansion of high-throughput technology platforms including circulating tumour DNA/RNA and microRNA offer new opportunities to improve prediction models, particularly in women with oestrogen receptor-negative disease and premenopausal women. Genomic assays have clearly improved prognostication of early oestrogen receptor-positive breast cancer but it is clear that standard clinicopathological parameters are still very important when identifying patient for adjuvant chemotherapy.is work has been supported by Cancer Research U
Identifying Biomarkers to Select Patients with Early Breast Cancer Suitable for Extended Adjuvant Endocrine Therapy
No full textPostmenopausal women with early oestrogen receptor-positive breast cancer who have received 5 years of endocrine therapy are at increased risk of developing a recurrence. An important clinical question is how to identify women who are at highest (or lowest) risk of a recurrence. The use of prognostic biomarkers allows individualised breast cancer therapy but correct identification of patients who will benefit most from extended endocrine therapy is essential. Several multigene assays have been developed to determine the likelihood of overall recurrence but so far none exist specifically for the prediction of late recurrence. Recent results from large clinical trials have shown that biomarker assays that include clinical information in their tests might be useful to predict and risk stratify patients for late recurrence. However, further research is needed to specifically offer multigene assays for the identification of late recurrence and thus justify routine use of these tests in the clinical setting.</jats:p
Breast cancer chemoprevention
No full textTrials with tamoxifen have clearly shown that the risk of developing oestrogen receptor positive breast cancer can be reduced by at least 50% with prophylactic agents. The current challenge is to find new agents which achieve this or better efficacy, but with fewer side effects. Recent results indicate that the SERM raloxifene has similar efficacy to tamoxifen, but leads to fewer endometrial cancers, gynecological symptoms, and thromboembolic events. Results for contralateral tumors in adjuvant trials suggest that aromatase inhibitors may be able to prevent up to 70%–80% of ER-positive breast cancers, and this is currently being investigated in two large prevention trials, one using anastrozole (IBIS-II) and the other exemestane (MAP.3). New agents are needed for receptor negative breast cancer and several possibilities are currently under investigation
Integration of Clinical Variables for the Prediction of Late Distant Recurrence in Patients With Estrogen Receptor-Positive Breast Cancer Treated With 5 Years of Endocrine Therapy: CTS5.
No full textPurpose Estimating risk of late distant recurrence (DR) is an important goal for managing women with hormone receptor-positive breast cancer after 5 years of endocrine treatment without recurrence. We developed and validated a simple clinicopathologic tool (Clinical Treatment Score post-5 years [CTS5]) to estimate residual risk of DR after 5 years of endocrine treatment. Patients and Methods The ATAC (Arimidex, Tamoxifen, Alone or in Combination) data set (N = 4,735) was used to create a prognostic score for post-5-year risk of DR. Validity of CTS5 (ATAC) was tested in the BIG 1-98 data set (N = 6,711). Time to late DR, 5 years after finishing scheduled endocrine therapy, was the primary end point. Cox regression models estimated the prognostic performance of CTS5 (ATAC). Results CTS5 (ATAC) was significantly prognostic for late DR in the ATAC cohort (hazard ratio, 2.47; 95% CI, 2.24 to 2.73; P 10%) identified 43% of the validation cohort as low risk, with an observed DR rate of 3.6% (95% CI, 2.7% to 4.9%) during years 5 to 10. From years 5 to 10, 63% of node-negative patients were low risk, with a DR rate of 3.9% (95% CI, 2.9% to 5.3%), and 24% with one to three positive nodes were low risk, with a DR rate of 1.5% (95% CI, 0.5% to 3.8%). A final CTS5 for future use was derived from pooled data from ATAC and BIG 1-98. Conclusion CTS5 is a simple tool based on information that is readily available to all clinicians. CTS5 was validated as highly prognostic for late DR in the independent BIG 1-98 study. The final CTS5 algorithm identified 42% of women with < 1% per-year risk of DR who could be advised of the limited potential value of extended endocrine therapy
User's guide for the Yield Estimation Subsystem Data Management System (YESDAMS)
No full textThere are no author-identified significant results in this report
Cure Induced Property Changes and Warpage in Thermoset Resins and Composites
No full textThe
aim of the present work was to investigate the evolution of thermal and
mechanical properties during the polymerisation of a thermosetting resin that is typical
those used as the matrix
in
advanced composites. The
mechanism of the cure reaction
was studied using
differential
scanning calorimetry
(DSC) in both dynamic (thermal
scanning) and
isothermal
modes, and procedures
for
correlating the two types of
calorimetric
data were
developed. The
model
finally
chosen encapsulates the diffusion-
controlled mechanism of reaction by
establishing a one-to-one relationship between the
degree of cure and the glass transition temperature, which
is
assumed to be
a structural
parameter during the polymerisation. A detailed
experimental investigation
of specific
heat
capacity, thermal
conductivity, secondary transformations (gelation
and
vitrification), thermal and chemical volume changes and stress relaxation moduli was
carried out to establish a suitable
database for the resin.
Where
possible, a closed
analytical model was employed; alternatively, an interpolation
procedure was developed
evaluate the changes in
a selected property
during
a more complex
temperature
profile.
Experimental
equipment was
developed to perform shrinkage measurements on
the neat resin system; the results obtained were
later
compared with experimental
data
from
standard liquid dilatometry tests.
A
simulation of the curing of a bi-material
cantilever beam is
presented as a test case
highlight the influence
of property changes on the final
curvature. Sample curvature
during the experiment was recorded using a
digital
camera and then analysed using
graphical software.
The
correlation
between the observed values of curvature and the
results of a
finite
element based simulation was used to validate the kinetics model and
property modelling
for the chosen thermosetting resin
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