The relationships among breast density, age, and use of hormone replacement therapy (HRT) in breast cancer detection have not been fully evaluated.
To determine how breast density, age, and use of ...HRT individually and in combination affect the accuracy of screening mammography.
Prospective cohort study.
7 population-based mammography registries in North Carolina; New Mexico; New Hampshire; Vermont; Colorado; Seattle, Washington; and San Francisco, California.
329 495 women 40 to 89 years of age who had 463 372 screening mammograms from 1996 to 1998; 2223 women received a diagnosis of breast cancer.
Breast density, age, HRT use, rate of breast cancer occurrence, and sensitivity and specificity of screening mammography.
Adjusted sensitivity ranged from 62.9% in women with extremely dense breasts to 87.0% in women with almost entirely fatty breasts; adjusted sensitivity increased with age from 68.6% in women 40 to 44 years of age to 83.3% in women 80 to 89 years of age. Adjusted specificity increased from 89.1% in women with extremely dense breasts to 96.9% in women with almost entirely fatty breasts. In women who did not use HRT, adjusted specificity increased from 91.4% in women 40 to 44 years of age to 94.4% in women 80 to 89 years of age. In women who used HRT, adjusted specificity was about 91.7% for all ages.
Mammographic breast density and age are important predictors of the accuracy of screening mammography. Although HRT use is not an independent predictor of accuracy, it probably affects accuracy by increasing breast density.
Conflicting expert recommendations regarding cancer screening and prevention are growing in number, visibility, and importance,
but their impact are not well understood. In this study, we examined ...the impact of conflicting recommendations about mammography
screening on women's mammography behavior and perceptions. We conducted a secondary analysis of longitudinal data from the
1995 Maximizing Mammography Participation Trial, a large randomized interventional trial examining the effectiveness of patient
reminders in increasing mammography utilization among women ages 50 to 79. Using the decision theory concept of “ambiguity”
as an analytic framework, we tested several predictions about the effects of conflicting recommendations regarding mammography
recommendations on behavior, cognitions, and emotions related to mammography screening. We found high perceived ambiguity
about mammography recommendations to be associated with both diminished uptake of mammography over time odds ratio (OR),
0.42; 95% confidence interval (95% CI), 0.23-0.76; P < 0.0001 and lower intentions for future mammography (OR, 0.34; 95% CI, 0.20-0.55; P < 0.0001). High perceived ambiguity also predicted greater mammography-related worry over time (OR, 2.60; 95% CI, 1.79-3.78;
P < 0.0001). These findings suggest that conflicting recommendations regarding cancer screening and prevention have important
effects, and we discuss the implications of these findings for future research. (Cancer Epidemiol Biomarkers Prev 2007;16(3):458–66)
Health care in the United States is notoriously expensive while often failing to deliver the care recommended in published guidelines. There is, therefore, a need to consider our approach to ...health-care delivery. Cancer care is a good example for consideration because it spans the continuum of health-care issues from primary prevention through long-term survival and end-of-life care. In this monograph, we emphasize that health-care delivery occurs in a multilevel system that includes organizations, teams, and individuals. To achieve health-care delivery consistent with the Institute of Medicine's six quality aims (safety, effectiveness, timeliness, efficiency, patient-centeredness, and equity), we must influence multiple levels of that multilevel system. The notion that multiple levels of contextual influence affect behaviors through interdependent interactions is a well-established ecological view. This view has been used to analyze health-care delivery and health disparities. However, experience considering multilevel interventions in health care is much less robust. This monograph includes 13 chapters relevant to expanding the foundation of research for multilevel interventions in health-care delivery. Subjects include clinical cases of multilevel thinking in health-care delivery, the state of knowledge regarding multilevel interventions, study design and measurement considerations, methods for combining interventions, time as a consideration in the evaluation of effects, measurement of effects, simulations, application of multilevel thinking to health-care systems and disparities, and implementation of the Affordable Care Act of 2010. Our goal is to outline an agenda to proceed with multilevel intervention research, not because it guarantees improvement in our current approach to health care, but because ignoring the complexity of the multilevel environment in which care occurs has not achieved the desired improvements in care quality outlined by the Institute of Medicine at the turn of the millennium.
Androgen deprivation therapy (ADT), an important treatment for advanced prostate cancer, is highly variable in its effectiveness. We hypothesized that genetic variants of androgen transporter genes, ...SLCO2B1 and SLCO1B3, may determine time to progression on ADT.
A cohort of 538 patients with prostate cancer treated with ADT was genotyped for SLCO2B1 and SLCO1B3 single nucleotide polymorphisms (SNP). The biologic function of a SLCO2B1 coding SNP in transporting androgen was examined through biochemical assays.
Three SNPs in SLCO2B1 were associated with time to progression (TTP) on ADT (P < .05). The differences in median TTP for each of these polymorphisms were about 10 months. The SLCO2B1 genotype, which allows more efficient import of androgen, enhances cell growth and is associated with a shorter TTP on ADT. Patients carrying both SLCO2B1 and SLCO1B3 genotypes, which import androgens more efficiently, exhibited a median 2-year shorter TTP on ADT, demonstrating a gene-gene interaction (P(interaction) = .041).
Genetic variants of SLCO2B1 and SLCO1B3 may function as pharmacogenomic determinants of resistance to ADT in prostate cancer.
In metastatic castration-resistant prostate cancer (mCRPC) low serum androgens prior to starting abiraterone acetate (AA) is associated with more rapid progression. We evaluated the effect of AA on ...androgens in castration-resistant prostate cancer (CRPC) metastases and associations of intratumoral androgens with response.
We performed a phase II study of AA plus prednisone in mCRPC. The primary outcome was tissue testosterone at 4 weeks. Exploratory outcomes were association of steroid levels and genomic alterations with response, and escalating AA to 2,000 mg at progression.
Twenty-nine of 30 men were evaluable. Testosterone in metastatic biopsies became undetectable at 4 weeks (
< 0.001). Serum and tissue dehydroepiandrosterone sulfate (DHEAS) remained detectable in many patients and was not increased at progression. Serum and tissue DHEAS in the lowest quartile (pretreatment), serum DHEAS in the lowest quartile (4 weeks), and undetectable tissue DHEAS (on-therapy) associated with rapid progression (20 vs. 48 weeks,
= 0.0018; 20 vs. 52 weeks,
= 0.0003; 14 vs. 40 weeks,
= 0.0001; 20 vs. 56 weeks,
= 0.02, respectively). One of 16 men escalating to 2,000 mg had a 30% PSA decline; 13 developed radiographic progression by 12 weeks. Among patients with high serum DHEAS at baseline, wild-type (WT) PTEN status associated with longer response (61 vs. 33 weeks,
= 0.02).
Low-circulating adrenal androgen levels are strongly associated with an androgen-poor tumor microenvironment and with poor response to AA. Patients with CRPC with higher serum DHEAS levels may benefit from dual androgen receptor (AR)-pathway inhibition, while those in the lowest quartile may require combinations with non-AR-directed therapy.
High-risk localized prostate cancer (HRLPC) is associated with a substantial risk of recurrence and disease mortality. Recent clinical trials have shown that intensifying anti-androgen therapies ...administered before prostatectomy can induce pathologic complete responses or minimal residual disease, called exceptional response, although the molecular determinants of these clinical outcomes are largely unknown. Here, we perform whole-exome and transcriptome sequencing on pre-treatment multi-regional tumor biopsies from exceptional responders (ERs) and non-responders (NRs, pathologic T3 or lymph node-positive disease) to intensive neoadjuvant anti-androgen therapies. Clonal SPOP mutation and SPOPL copy-number loss are exclusively observed in ERs, while clonal TP53 mutation and PTEN copy-number loss are exclusively observed in NRs. Transcriptional programs involving androgen signaling and TGF-β signaling are enriched in ERs and NRs, respectively. These findings may guide prospective validation studies of these molecular features in large HRLPC clinical cohorts treated with neoadjuvant anti-androgens to improve patient stratification.
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•SPOP mutation and SPOPL copy-number loss are exclusive to exceptional responders•Androgen signaling expression programs are enriched in exceptional responders•Non-responders harbor TP53 mutation, PTEN loss, and TGF-β transcriptional programs•Phylogenetic analysis reveals that key response mediators are truncal in nature
Leveraging pretreatment multi-regional biopsies from patients with high-risk localized prostate cancer, Tewari et al. identify whole-exome and transcriptional features associated with exceptional response and non-response to neoadjuvant androgen pathway inhibition. These results may have major stratification and treatment implications for this large patient population.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Prostate cancer is the most commonly diagnosed malignant condition and the second leading cause of cancer-related death in American men.
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In its early stage the disease is sometimes curable by ...radical prostatectomy or radiation therapy. However, metastases are common at presentation and they ultimately afflict many patients who were treated with curative intent when they had early-stage disease. The only effective treatment for metastatic prostate cancer is reduction of testosterone and 5α-dihydrotestosterone concentrations (androgen ablation), by either orchiectomy or the administration of an agonist of luteinizing hormone–releasing hormone (LHRH). The rate of response to androgen ablation can be as high . . .
This summary reflects on this monograph regarding multilevel intervention (MLI) research to 1) assess its added value; 2) discuss what has been learned to date about its challenges in cancer care ...delivery; and 3) identify specific ways to improve its scientific soundness, feasibility, policy relevance, and research agenda. The 12 submitted chapters, and discussion of them at the March 2011 multilevel meeting, were reviewed and discussed among the authors to elicit key findings and results addressing the questions raised at the outset of this effort. MLI research is underrepresented as an explicit focus in the cancer literature but may improve implementation of studies of cancer care delivery if they assess contextual, organizational, and environmental factors important to understanding behavioral and/or system-level interventions. The field lacks a single unifying theory, although several psychological or biological theories are useful, and an ecological model helps conceptualize and communicate interventions. MLI research designs are often complex, involving nonlinear and nonhierarchical relationships that may not be optimally studied in randomized designs. Simulation modeling and pilot studies may be necessary to evaluate MLI interventions. Measurement and evaluation of team and organizational interventions are especially needed in cancer care, as are attention to the context of health-care reform, eHealth technology, and genomics-based medicine. Future progress in MLI research requires greater attention to developing and supporting relevant metrics of level effects and interactions and evaluating MLI interventions. MLI research holds an unrealized promise for understanding how to improve cancer care delivery.
Although systems strategies are effective in improving health care delivery, little is known about their use for cancer screening in U.S. primary care practice.
We assessed primary care physicians' ...(N = 2,475) use of systems strategies for breast, cervical, and colorectal cancer (CRC) screening in a national survey conducted in 2007. Systems strategies included patient and physician screening reminders, performance reports of screening rates, electronic medical records, implementation of in-practice guidelines, and use of nurse practitioners/physician assistants. We evaluated use of both patient and physician screening reminders with other strategies in separate models by screening type, adjusted for the effects of physician and practice characteristics with multivariate logistic regression.
Fewer than 10% of physicians used a comprehensive set of systems strategies to support cancer screening; use was greater for mammography and Pap testing than for CRC screening. In adjusted analyses, performance reports of cancer screening rates, medical record type, and in-practice guidelines were associated with use of both patient and physician screening reminders for mammography, Pap testing, and CRC screening (P < 0.05).
Despite evidence supporting use of systems strategies in primary care, few physicians report using a comprehensive set of strategies to support cancer screening.
Current health policy initiatives underscore the importance of increased implementation of systems strategies in primary care to improve the use and quality of cancer screening in the United States.
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