Although functional status serves as a major predictor of morbidity, researchers and clinicians use different terms and measures, limiting comparisons across studies. To demonstrate how differing measures may generate varied findings, we compared and contrasted data from the SF-12 Health Survey Physical Component Summary Scale (SF-12 PCS) and the Enforced Social Dependency Scale (ESDS). The sample consisted of 49 women ages 65 and over recovering from gynecological cancer surgery with data collection at baseline (postoperative period) then 3 and 6 months. Analysis of the relationship between SF-12 PCS and ESDS over time using Generalized Estimating Equations (GEE) demonstrated the relationship was less than 1.0, signaling less than perfect agreement between measures (Beta=0.16, p=0.002). These findings suggest that that the two measures are not interchangeable and may produce conflicting evidence. This highlights the importance of researchers' and clinicians' careful conceptualization and operationalization of functional status prior to measure selection.
Hospital rankings have become integral to the marketing strategies of many health care systems. Methodology used in compiling these lists appears highly flawed.
Improve on current hospital ranking systems and to develop a more meaningful measure of a urology department’s contribution to the field, we developed an academic ranking score (ARS) based on publicly available data.
Design, setting, and participants
An active faculty list was assembled for each department. A list of all publications from each department from 2005 to 2010 was then compiled. Only publications with faculty members as first or last author were considered. The ARS was then derived by identifying the number of publications within an institution, normalized by the impact factor of the peer-reviewed journal in which the publication appeared.
The 2010 U.S. News and World Report (USNWR) urology list was reranked based on ARS and compared with the USNWR rank list. ARS was also calculated for several leading European urologic centers.
Results and limitations
A total of 6437 urologic publications were indexed to calculate the ARS. Two of the top three programs in the USNWR rankings dropped out of the top 10. The top 10 academically ranked programs increased or decreased an average of >5 positions (range: 0–17). No correlation was seen between programs ranked in the top 10 by USNWR and our objective ARS method (Spearman ρ: −0.1; p = 0.75). Because ARS only includes first- or last-author publications for faculty with clinical duties, ARS likely excludes basic science contributions and contributions from nonclinical faculty.
Ranking of urology departments through quantification of each program’s recent academic contribution, as captured by the ARS, differs substantially from rankings developed by USNWR. Integration of such objective measures into an overall urology program ranking system would replace current subjective opinions marred by historical biases with up-to-date merit-based assessments.
Response fatigue can cause measurement error and misclassification problems in survey research. Questions asked later in a long survey are often prone to more measurement error or misclassification. The response given is a function of both the true response and participant response fatigue. We investigate the identifiability of survey order effects and their impact on estimators of treatment effects. The focus is on fatigue that affects a given answer to a question rather than fatigue that causes non-response and missing data. We consider linear, Gamma, and logistic models of response that incorporate both the true underlying response and the effect of question order. For continuous data, survey order effects have no impact on study power under a Gamma model. However, under a linear model that allows for convergence of responses to a common mean, the impact of fatigue on power will depend on how fatigue affects both the rate of mean convergence and the variance of responses. For binary data and for less than a 50% chance of a positive response, order effects cause study power to increase under a linear probability (risk difference) model, but decrease under a logistic model. The results suggest that measures designed to reduce survey order effects might have unintended consequences. We present a data example that demonstrates the problem of survey order effects.
Robotic surgery has been widely adopted for radical prostatectomy. We hypothesize that this change is rapidly shifting procedures away from hospitals that do not offer robotics and consequently increasing patient travel.
A population-based observational study of all prostatectomies for cancer in NY, NJ, and PA from 2000–2009 was performed using hospital discharge data. Hospital procedure volume was defined as the number of prostatectomies performed for cancer in a given year. Straight-line travel distance to treating hospital was calculated for each case. Hospitals were contacted to determine year of acquisition of first robot.
From 2000–2009, the total number of prostatectomies performed annually increased substantially. The increase occurred almost entirely at the very high volume centers (≥106 prostatectomies/year). The number of hospitals performing prostatectomy fell 37% from 2000–2009. By 2009, the 9% (21/244) of hospitals that had very high volume performed 57% of all prostatectomies, and the 35% (86/244) of hospitals with a robot performed 85% of all prostatectomies. Median travel increased 54% from 2000–2009, p<0.001. The proportion of patients traveling ≥15 miles increased from 24% to 40%, p<0.001.
Over the past decade, the number of radical prostatectomies performed has risen substantially. These procedures have been increasingly centralized at high volume centers, leading to longer patient travel distances. Few prostatectomies are now performed at hospitals that do not offer robotic surgery. Future work should focus on the impact of these trends on cancer control, functional outcomes, access to care and cost.
One problem with assessing effects of smoking cessation interventions on withdrawal symptoms is that symptoms are affected by whether participants abstain from smoking during trials. Those who enter a randomized trial but do not change smoking behavior might not experience withdrawal related symptoms.
We present a tutorial of how one can use a principal stratification sensitivity analysis to account for abstinence in the estimation of smoking cessation intervention effects. The paper is intended to introduce researchers to principal stratification and describe how they might implement the methods.
We provide a hypothetical example that demonstrates why estimating effects within observed abstention groups is problematic. We demonstrate how estimation of effects within groups defined by potential abstention that an individual would have in either arm of a study can provide meaningful inferences. We describe a sensitivity analysis method to estimate such effects, and use it to investigate effects of a combined behavioral and nicotine replacement therapy intervention on withdrawal symptoms in a female prisoner population.
Overall, the intervention was found to reduce withdrawal symptoms but the effect was not statistically significant in the group that was observed to abstain. More importantly, the intervention was found to be highly effective in the group that would abstain regardless of intervention assignment. The effectiveness of the intervention in other potential abstinence strata depends on the sensitivity analysis assumptions.
We make assumptions to narrow the range of our sensitivity parameter estimates. While appropriate in this situation, such assumptions might not be plausible in all situations.
A principal stratification sensitivity analysis provides a meaningful method of accounting for abstinence effects in the evaluation of smoking cessation interventions on withdrawal symptoms. Smoking researchers have previously recommended analyses in subgroups defined by observed abstention status in the evaluation of smoking cessation interventions. We believe that principal stratification analyses should replace such analyses as the preferred means of accounting for post-randomization abstinence effects in the evaluation of smoking cessation programs.
Prognosis in renal cell carcinoma (RCC) is dependent on tumor stage at presentation, with significant differences in survival between early and late stage disease. Currently, there are no screening tests or biomarkers identified for the early detection of kidney cancer. Here, we investigate if serum amino acid profiles are a potentially useful biomarker in patients with RCC.
Materials and Methods
The concentrations of 26 different amino acids were determined in serum taken pre-operatively from 189 RCC patients and 104 age and sex matched controls.
Statistically significant changes were observed in patient levels of 15 different amino acids, with 13 being decreased and two being elevated. A logistic regression model utilizing eight amino acids including cysteine, ornithine, histidine, leucine, tyrosine, proline, valine and lysine was created to distinguish cases from controls. A receiver operator curve based on this model had an area under the curve of 0.81. This same model also had predictive value in predicting overall survival and tumor recurrence in RCC patients.
Our findings suggest that serum amino acid levels may be useful as a screening tool for the identification of individuals with RCC and predicting patient outcomes.
Kidney Cancer; biomarker; serum; amino acids
Counseling patients with enhancing renal mass currently occurs in the context of significant uncertainty regarding tumor pathology.
We evaluated whether radiographic features of renal masses could predict tumor pathology and developed a comprehensive nomogram to quantitate the likelihood of malignancy and high-grade pathology based on these features.
Design, setting, and participants
We retrospectively queried Fox Chase Cancer Center’s prospectively maintained database for consecutive renal masses where a Nephrometry score was available.
All patients in the cohort underwent either partial or radical nephrectomy.
The individual components of Nephrometry were compared with histology and grade of resected tumors. We used multiple logistic regression to develop nomograms predicting the malignancy of tumors and likelihood of high-grade disease among malignant tumors.
Results and limitations
Nephrometry score was available for 525 of 1750 renal masses. Nephrometry score correlated with both tumor grade (p < 0.0001) and histology (p < 0.0001), such that small endophytic nonhilar tumors were more likely to represent benign pathology. Conversely, large interpolar and hilar tumors more often represented high-grade cancers. The resulting nomogram from these data offers a useful tool for the preoperative prediction of tumor histology (area under the curve [AUC]: 0.76) and grade (AUC: 0.73). The model was subjected to out-of-sample cross-validation; however, lack of external validation is a limitation of the study.
The current study is the first to objectify the relationship between tumor anatomy and pathology. Using the Nephrometry score, we developed a tool to quantitate the preoperative likelihood of malignant and high-grade pathology of an enhancing renal mass.
Kidney; Carcinoma; Renal cell; Nomograms; Nephrometry; Anatomy
Antimüllerian hormone (AMH) is extensively studied in ovarian aging and pathology; however, little is known about correlates in healthy premenopausal women. We found that AMH levels are strongly inversely associated with age and differed significantly between oral contraceptive pill users and nonusers, whereas no significant associations were seen between AMH and other clinical, behavioral, and anthropometric characteristics and laboratory variables, making it an attractive hormone for clinical applications.
Müllerian-inhibiting substance (MIS); antimüllerian hormone (AMH); ovary; premenopausal; healthy
Dr. Pearl invites researchers to justify their use of principal stratification. This comment explains how the use of principal stratification simplified a complex mediational problem encountered when evaluating a smoking cessation intervention's effect on reducing smoking withdrawal symptoms.
causal inference; principal stratification; mediation; smoking cessation interventions
Combining extant datasets with differing outcome measures, an economical method to generate evidence guiding older adults’ cancer care, may introduce heterogeneity leading to invalid study results. We recently conducted a study combining extant datasets from five oncology nurse-directed clinical trials (parent studies) using norm-based scoring to standardize the differing outcome measures. The purpose of this article is to describe and analyze our methods in the recently completed study. Despite addressing and controlling for heterogeneity, our analysis found statistically significant heterogeneity (p<0.0001) in temporal trends among the five parent studies. We concluded that assessing heterogeneity in combined extant datasets with differing outcome measures is important to ensure similar magnitude and direction of findings across parent studies. Future research should include investigating reasons for heterogeneity to generate hypotheses about subgroup differences or differing measurement domains that may have an impact on outcomes.
Combining data; Older Adults; Cancer
To explore factors influencing functional status over time after cancer surgery in adults aged 65 and older.
Secondary data analysis of combined data subsets.
Five prospective, longitudinal oncology nurse-directed clinical studies conducted at three academic centers in the northwest and northeast United States.
Three hundred sixteen community-residing patients diagnosed with digestive system, thoracic, genitourinary, and gynecological cancers treated primarily with surgery.
Functional status, defined as performance of current life roles, was measured using the Enforced Social Dependency Scale and the Medical Outcomes Study 36-item Short-Form Survey (using physical component summary measures) after surgery (baseline) and again at 3 and 6 months. Number of symptoms, measured using the Symptom Distress Scale, quantified the effect of each additional common cancer symptom on functional status.
After controlling for cancer site and stage, comorbidities, symptoms, psychological status, treatment, and demographic variables, functional status was found to be significantly better at 3 and 6 months after surgery than at baseline. Factors associated with better functional status included higher income and better mental health. Factors associated with poorer average functional status were a greater number of symptoms and comorbidities. Persons reporting three or more symptoms experienced statistically significant and clinically meaningful poorer functional status than those without symptoms. Persons reporting three or more comorbidities were also found to have poorer functional status than those without comorbidities. No significant relationship existed between age and functional status in patients aged 65 and older.
Factors other than age affect recovery of functional status in older adults after cancer surgery.
functional status; older adult; cancer surgery
Elevated expression of the Nedd9/HEF1/Cas-L scaffolding protein promotes tumor cell invasion and metastasis in multiple cancer cell types. Conversely, generation of mammary tumors in the MMTV-polyoma virus middle T (PyVT) genetic model is delayed by a Nedd9−/− genotype. These activities arise from the role of Nedd9 in assembling complexes and supporting activity of cancer signaling proteins including FAK, SRC, SHC, and AKT, and would support evaluation of Nedd9 expression as an unambiguous biomarker for tumor aggressiveness. However, we here show that despite the initial delay in tumor growth, cells derived from MMTV-PyVT;Nedd9−/− tumors are characteristically hyperaggressive versus MMTV-PyVT;Nedd9+/+ cells in anchorage-independent growth, growth on 3D matrix produced by tumor-associated fibroblasts, and in formation of tumors after mammary orthotopic reinjection, and of lung metastases after tail vein injection. This reversal suggests the specific selection of MMTV-PyVT;Nedd9−/− cells for growth in an in vivo microenvironment. Indeed, MMTV-PyVT;Nedd9−/− cells have increased cell cycle, centrosomal, and mitotic defects, phenotypes compatible with the increased selection of these cells for aggressive growth. Intriguingly, in spite of their aggressive phenotype, MMTV-PyVT;Nedd9−/− cells persistently have low levels of SRC activation and are hypersensitive to the SRC kinase inhibitor dasatinib. These studies identify Nedd9 as a complex modulator of different aspects of mammary tumor growth.
A systematic review and meta-analysis to investigate the efficacy of interventions incorporating motivational interviewing for smoking cessation and identify correlates of treatment effects.
MEDLINE/PubMed, PsycInfo, and other sources including grey literature.
Title/abstract search terms were motivational interview* OR motivational enhancement AND smok*, cigarette*, tobacco, OR nicotine. Randomized trials reporting number of smokers abstinent at follow up were eligible.
Data were independently coded by the first and third authors. We coded for a variety of study, participant, and intervention related variables.
A random effects logistic regression with both a random intercept and a random slope for the treatment effect.
Thirty-one smoking cessation research trials were selected for the study: 8 comprised adolescent samples, 8 comprised adults with chronic physical or mental illness, 5 comprised pregnant/postpartum women, and 10 comprised other adult samples. Analysis of the trials (9,485 individual participants) showed an overall odds ratio comparing likelihood of abstinence in the MI versus control condition of OR=1.45, 95% Confidence Interval or CI = 1.14-1.83). Additional potential correlates of treatment effects such as study, sample, and intervention characteristics were examined.
This is the most comprehensive review of MI for smoking cessation conducted to-date. These findings suggest that current MI smoking cessation approaches can be effective for adolescents and adults. However, comparative efficacy trials could be useful.
Motivational Interviewing; Smoking Cessation; Systematic Review; Meta-Analysis
Prospective randomized trials have demonstrated a survival benefit for nephrectomy in patients with metastatic renal cell carcinoma treated with immunotherapy. These data have been extrapolated to support cytoreductive nephrectomy in the targeted therapy era as well. However, the likelihood that patients with metastatic kidney cancer who undergo nephrectomy will receive systemic treatment postoperatively remains poorly defined. We present a multi-institutional experience evaluating the utilization of systemic therapy in patients undergoing cytoreductive nephrectomy.
PATIENTS AND METHODS
141 patients who underwent cytoreductive nephrectomy between 1990 and 2008 were identified from our Institutional Kidney Cancer Registries. Kaplan Meier analyses and Cox regression models were used to assess the impact of clinicopathological and perioperative variables on patients’ subsequent receipt of systemic therapy and postoperative survival.
Overall, 98/141 patients (69.5%) received postoperative systemic treatment, at a median of 2.5 months (range 0.1–61.5) after nephrectomy. In this group, 52 (53%) patients received immunotherapy, 34 (35%) targeted agents, and 12 (12%) other regimens. By contrast, 43 patients (30.5%) did not receive systemic therapy, because of rapid disease progression (n=13, 30%), decision for surveillance by medical oncology (n=9, 21%), patient refusal (n=10, 23%), perioperative mortality (n=8, 19%), and unknown reasons in three patients (7.0%). Median survival following cytoreductive nephrectomy was 16.7 months (range 0–120). The risk of death after surgery correlated with the number of metastatic sites (p=0.012) and symptoms (p=0.001) at presentation, poor performance status (p=0.001), high tumor grade (p=0.006), and presence of sarcomatoid features (p<0.024).
Nearly one-third of patients undergoing cytoreductive nephrectomy did not receive systemic treatment. While some were electively observed or declined therapy, others did not receive treatment due to rapidly progressive disease. Further investigation is warranted to identify those patients at highest risk for rapid post-operative disease progression who might benefit instead from an initial approach to treatment with systemic therapy.
renal cell carcinoma; metastases; nephrectomy; systemic therapy; targeted therapy
To assess reproducibility of a commercial mullerian inhibiting substance (MIS) assay and evaluate within-person variation in serum MIS levels.
Assay reproducibility was evaluated by measuring MIS in multiple serum aliquots from the same blood collection. Within-person variation was assessed by measuring MIS in serum collected twice from the same individuals.
Fox Chase Cancer Center, Philadelphia, PA
Assay reproducibility was evaluated using serum from 5 volunteers with regular menstrual cycles. Within-person variation was evaluated in serum from 20 premenopausal women who donated blood twice at least 1 year apart.
For both studies, samples were randomly ordered in batches and laboratory personnel were blinded to which aliquots were from the same subject.
Main Outcome Measure(s)
MIS was measured using an enzyme-linked immunosorbent assay.
Within- and between-batch coefficients of variation (CVs) of the assay were 7.9% and 12.3%, respectively. After deleting one subject with extreme values, these CVs decreased to 7.6% and 7.7%, respectively. Within- and between-subject variance in MIS measurements were 2.19 and 0.31, respectively, and the intraclass correlation coefficient was .88 (95% confidence interval = .77 – .98).
MIS serum concentration is relatively stable over one year in premenopausal women and can be measured with good reproducibility using a commercial kit.
Mullerian inhibiting substance (MIS); anti-mullerian hormone (AMH); assay reproducibility; coefficient of variation (CV); within-person variation; intraclass correlation coefficient (ICC)
Circulating levels of bioavailable estradiol and testosterone are often desirable for clinical practice or investigational studies of children. However, assays to measure circulating hormone levels might not always be accessible. We sought to validate the empirical calculation of circulating bioavailable testosterone and estradiol in children.
663 eight to ten year olds were recruited to the Dietary Intervention Study in Children (DISC). DISC was a randomized clinical trial designed to test efficacy of a dietary intervention to reduce serum cholesterol (LDL-C) in children with elevated cholesterol. Assay measures of estradiol, testosterone, sex hormone-binding globulin concentration (SHBG), and albumin concentration in girls as well as dihydrotestosterone in boys were measured for up to 10 years. We calculated measures of circulating non-SHBG bound estradiol and testosterone from total hormone levels using the law of mass action. We compared proportional differences in assay measured minus calculated non-SHBG bound hormone levels versus their averages using GEE-estimated linear regressions.
On average, calculated values overestimated assay measured values (−11.7% for non-SHBG bound estradiol in girls and −2.6% for non-SHBG bound testosterone in boys). The intercept and slope of the regression for non-SHBG bound estradiol in girls were −0.13 (95% CI −0.14 to −0.12) and 0.005 (95% CI 0.003 to 0.007), respectively. The intercept and slope for non-SHBG bound testosterone in boys were −0.16 (95% CI −0.17 to −0.14) and 0.0006 (95% CI 0.0005–0.0006).
While calculated values might be useful for research purposes, they are generally not close enough for clinical purposes.
Clinical factors in addition to PSA have been evaluated to improve risk assessment for prostate cancer. The Prostate Cancer Prevention Trial (PCPT) risk calculator provides an assessment of prostate cancer risk based on age, PSA, race, prior biopsy, and family history. This study evaluated the risk calculator in a screening cohort of young, racially diverse, high-risk men with a low baseline PSA enrolled in the Prostate Cancer Risk Assessment Program.
Patients and Methods
Eligibility for PRAP include men ages 35-69 who are African-American, have a family history of prostate cancer, or have a known BRCA1/2 mutation. PCPT risk scores were determined for PRAP participants, and were compared to observed prostate cancer rates.
624 participants were evaluated, including 382 (61.2%) African-American men and 375 (60%) men with a family history of prostate cancer. Median age was 49.0 years (range 34.0-69.0), and median PSA was 0.9 (range 0.1-27.2). PCPT risk score correlated with prostate cancer diagnosis, as the median baseline risk score in patients diagnosed with prostate cancer was 31.3%, versus 14.2% in patients not diagnosed with prostate cancer (p<0.0001). The PCPT calculator similarly stratified the risk of diagnosis of Gleason score ≥7 disease, as the median risk score was 36.2% in patients diagnosed with Gleason ≥7 prostate cancer versus 15.2% in all other participants (p<0.0001).
PCPT risk calculator score was found to stratify prostate cancer risk in a cohort of young, primarily African-American men with a low baseline PSA. These results support further evaluation of this predictive tool for prostate cancer risk assessment in high-risk men.
Prostate Cancer; prostate biopsy; prostate cancer prevention
Many patients with localized node-negative renal cell carcinoma (RCC) are elderly with competing comorbidities. Their overall survival benefit after surgical treatment is unknown. We reviewed cases in the Surveillance, Epidemiology, and End Results (SEER) database to evaluate the impact of kidney cancer versus competing causes of death in patients with localized RCC and develop a comprehensive nomogram to quantitate survival differences.
We identified individuals with localized, surgically treated clear-cell, papillary, or chromophobe RCC in SEER (1988 through 2003). We used Fine and Gray competing risks proportional hazards regressions to predict 5-year probabilities of three competing mortality outcomes: kidney cancer death, other cancer death, and noncancer death.
We identified 30,801 cases of localized RCC (median age, 62 years; median tumor size, 4.5 cm). Five-year probabilities of kidney cancer death, other cancer death, and noncancer death were 4%, 7%, and 11%, respectively. Age was strongly predictive of mortality and most predictive of nonkidney cancer deaths (P < .001). Increasing tumor size was related to death from RCC and inversely related to noncancer deaths (P < .001). Racial differences in outcomes were most pronounced for nonkidney cancer deaths (P < .001). Men were more likely to die than women from all causes (P < .002). This nomogram integrates commonly available factors into a useful tool for comparing competing risks of death.
Management of localized RCC must consider competing causes of mortality, particularly in elderly populations. Effective decision making requires treatment trade-off calculations. We present a tool to quantitate competing causes of mortality in patients with localized RCC.
To describe and compare the causal beliefs and attributions about breast and colorectal cancer among unaffected women in the general population.
A total of 439 unaffected women in the general population were recruited to complete a web-based survey assessing causal beliefs for either breast (N = 211) or colorectal cancer (N = 228).
Heredity was ranked as the most important causal factor, followed by diet or eating habits for both cancer sites. Women endorsed the following causes of breast or colorectal cancer respectively: heredity (84.4%, 78.5%), diet or eating habits (46.4%, 69.7%), pollution in the environment (57.6%, 40.3%), aging (48.8%, 57.5%), alcohol (29.9%, 40.8%), smoking (58.3%, 50.8%), stress (27.5%, 29.4%), and lack of exercise (35.7%, 44.3%). Other factors such as prior surgery on the breast (23.7%) and colon (32.9%), or changes in one’s immune system (60.6% - breast; 59.2% - colon) were also endorsed by some women. Significant differences in the degree of endorsement for various causes of breast and colorectal cancer were identified.
Both genetic and environmental causes for breast and colorectal cancer are endorsed by unaffected women. Misconceptions about the causes of these cancers are important targets for public education and risk communication efforts.
breast and colorectal cancer; causal beliefs; attributions; risk factors; knowledge
Lung cancer is the leading cause of cancer mortality in women worldwide. Although the rise and growing epidemic status of this disease is overwhelmingly attributed to tobacco use, the rank of lung cancer in nonsmokers as the seventh most common cause of cancer worldwide suggests that other factors contribute to this disease. The majority of lung cancers among nonsmokers occur in women. Aside from geographic, cultural and genetic differences, hormonal and possibly infectious factors may also play etiologic roles. This review aims to discuss the epidemiology of lung cancer in women as well as the incidence of second primaries, and presents current opinions on the myriad of causes.
Purpose: This study was undertaken to describe cancer risk assessment practices among primary care providers (PCPs). Methods: An electronic survey was sent to PCPs affiliated with a single insurance carrier. Demographic and practice characteristics associated with cancer genetic risk assessment and testing activities were described. Latent class analysis supported by likelihood ratio tests was used to define PCP profiles with respect to the level of engagement in genetic risk assessment and referral activity based on demographic and practice characteristics. Results: 860 physicians responded to the survey (39% family practice, 29% internal medicine, 22% obstetrics/gynecology (OB/GYN), 10% other). Most respondents (83%) reported that they routinely assess hereditary cancer risk; however, only 33% reported that they take a full, three-generation pedigree for risk assessment. OB/GYN specialty, female gender, and physician access to a genetic counselor were independent predictors of referral to cancer genetics specialists. Three profiles of PCPs, based upon referral practice and extent of involvement in genetics evaluation, were defined. Conclusion: Profiles of physician characteristics associated with varying levels of engagement with cancer genetic risk assessment and testing can be identified. These profiles may ultimately be useful in targeting decision support tools and services.
In the past 3 years, altered expression of the HEF1/CAS-L/NEDD9 scaffolding protein has emerged as contributing to cancer metastasis in multiple cancer types. However, while some studies have identified elevated NEDD9 expression as pro-metastatic, other work has suggested a negative role in tumor progression. We here show that the Nedd9 null genetic background significantly limits mammary tumor initiation in the MMTV-polyoma virus middle T (PyVmT) genetic model. Action of Nedd9 is tumor cell intrinsic, with immune cell infiltration, stroma, and angiogenesis unaffected. The majority of the late-appearing mammary tumors of MMTV-PyVmT;Nedd9-/- mice are characterized by depressed activation of proteins including AKT, SRC, FAK, and ERK, emphasizing an important role of Nedd9 as a scaffolding protein for these pro-oncogenic proteins. Analysis of cells derived from primary Nedd9+/+ and Nedd9-/- tumors demonstrated persistently reduced FAK activation, attachment, and migration, consistent with a role for NEDD9 activation of FAK in promoting tumor aggressiveness. This study provides the first in vivo evidence of a role for NEDD9 in breast cancer progression, and suggests that Nedd9 expression may provide a biomarker for tumor aggressiveness.
The benefit of breast MRI for newly diagnosed breast cancer patients is uncertain. This study characterized those receiving MRI versus those who did not, and reports on their short term surgical outcomes, including time to surgery, margin status, and mastectomy rate.
All patients seen in a multidisciplinary breast cancer clinic from July 2004 to December 2006 were retrospectively reviewed. Patients were evaluated by a radiologist, pathologist, and surgical, radiation, and medical oncologists.
Among 577 patients, 130 had pre-treatment MRIs. MRI use increased from 2004 (referent, 13%) versus 2005 (24%, p=0.014) and 2006 (27%, p=0.002). Patients having MRIs were younger (52.5 vs 59.0 y, p<0.001), but its use was not associated with preoperative chemotherapy, family history of breast or ovarian cancer, presentation, or tumor features. MRI was associated with a 22.4-day delay in pre-treatment evaluation (p=0.011). BCT was attempted in 320 of 419 patients with complete surgical data. The odds ratio for mastectomy, controlling for T size and stage, was 1.80 after MRI vs. no MRI (p=0.024). Patients having MRIs did not have fewer positive margins at lumpectomy (21.6%-MRI vs. 13.8%-no MRI, p=0.20), or conversions from BCT to mastectomy (9.8%-MRI vs. 5.9%-no MRI, p=0.35).
Breast MRI use was not confined to any particular patient group. MRI use was not associated with improved margin status or BCT attempts, but was associated with a treatment delay and increased mastectomy rate. Without evidence of improved oncologic outcome as a result, our study does not support the routine use of MRI to select patients or facilitate the performance of BCT.
Magnetic Resonance Imaging; Neoplasms, Breast; Cancer of the Breast; Mastectomy; Mastectomy, Segmental; Breast-Conserving Surgery; Outcome Measures; Neoplasm, Residual; Time Factors
This study examined the associations of free testosterone and family environment with delinquent and aggressive behaviors among adolescent boys and girls with elevated low-density lipoprotein (LDL)-cholesterol levels.
Participants were 164 boys and 180 girls (ages 11–14 years). The female parent provided ratings of family cohesion and child aggressive and delinquent behaviors. Tanner ratings of pubertal development were obtained during physical examination, and a blood sample was drawn for assessment of serum levels of free testosterone.
Hierarchical regression analyses revealed significant two-way interactions of free testosterone and family cohesion on delinquent behaviors among adolescent boys and girls. Specifically, under conditions of low family cohesion, free testosterone was positively associated with delinquent behaviors among boys, whereas no association between free testosterone and delinquent behavior was observed in families with high cohesion. In contrast, free testosterone was negatively associated with delinquent behaviors among adolescent girls in low cohesion families. For girls, family cohesion was negatively associated with aggressive behaviors; for boys, LDL-C was positively associated with aggressive behaviors.
Child gender and family environment factors appear to modify the associations between free testosterone and delinquent behaviors in adolescent boys and girls.
testosterone; delinquent behaviors; aggression; family cohesion