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Biomedical subjects

Usha Menon

Publications and source records attributed to Usha Menon.

At least 19 recordsLinked to original sources
PubMed2026

Plasma signals of lung tumor promotion for molecular cancer prevention.

Predicting lung cancer risk would enhance prevention trials. Although the Canakinumab Anti-inflammatory Thrombosis Outcome Study (CANTOS) trial demonstrated reduced lung cancer incidence with interleukin (IL)-1β inhibition, the high number needed to treat (NNT) to prevent lung cancer limits its use in unselected populations. Using machine learning, we identified a 14-protein plasma signature predicting lung cancer more than 5 years before diagnosis. The signature, validated across eight cohorts, was elevated in current smokers and individuals exposed to particulate matter (PM) and linked to lung myeloid and alveolar cells. In epidermal growth factor receptor (EGFR)-driven lung adenocarcinoma, diverse epithelial lineages converged on a keratin8+/claudin4+ alveolar transitional state (KAC), whose transcriptional programs correlated with signature emergence. Components of the signature were induced by PM, oncogenic EGFR, or IL-1β, whereas IL-1β inhibition restrained PM-driven KAC expansion and early tumorigenesis. In CANTOS, the signature identified individuals who seemed to benefit more from anti-IL-1β therapy, lowering the NNT threshold and nominating circulating signals of tumor promotion for prevention.

Humans↗
PubMed2025

Estimands for Clinical Effectiveness of Risk-Reducing Early Salpingectomy in Women With High Risk of Ovarian Cancer.

IMPORTANCE: Risk-reducing early-salpingectomy (RRES) and delayed oophorectomy (DO) is a novel 2-stage alternative prevention strategy to risk-reducing salpingo-oophorectomy (RRSO) that avoids detrimental consequences of premature menopause. However, direct data on the clinical effectiveness for ovarian cancer (OC) risk reduction are lacking. OBJECTIVE: To explore how to define clinical effectiveness from prospective cohort studies using the estimand framework and sample size requirements. DESIGN, SETTING, AND PARTICIPANTS: In this comparative effectiveness research study, estimand and analysis options were considered to evaluate the clinical effectiveness of RRES with DO by extending the UK PROTECTOR cohort study, a multicenter, prospective, observational, national cohort study (N = 1250 recruited from January 1, 2019, to December 31, 2024) evaluating RRES and DO for OC surgical prevention. Participants were premenopausal women 30 years or older at increased OC risk due to BRCA1/BRCA2 pathogenic variants. Participants could choose RRES, RRSO, or no surgery at entry. Sample size requirements used initial data (eg, age and BRCA1/2 distribution) from PROTECTOR (analysis undertaken from January 1, 2024, to December 31, 2025). MAIN OUTCOMES AND MEASURES: Incidence of OC after (not at) RRES and before or at DO in women with normal histologic analysis findings at surgery. The proportion of cancers prevented was estimated as the completement of the observed (O) to expected (E; assuming no preventive effect of surgery) number of cancers detected (1 - O/E). RESULTS: Initial data were obtained from 889 women in PROTECTOR (overall mean [SD] age, 39 [5] years), with 255 (28.7%) choosing RRSO (mean [SD] age, 42 [4] years), 405 (45.5%) choosing RRES (mean [SD] age, 38 [4] years), and 229 (25.7%) choosing no surgery (mean [SD], 38 [5] years). The preferred estimand outcome was OC incidence after surgery (RRES or RRSO) with a "while on intervention" strategy to account for intercurrent events. The primary target measure was the proportion of cancers prevented for RRES vs no surgery with superiority testing. The secondary target measure was noninferiority of RRES vs RRSO. An estimated 1150 RRES participants with 8 to 10 years of follow-up would provide approximately 92% power to show that 20% or more of cancers are prevented using a 1-sample binomial test of the O:E risk (external reference) at the 5% level under a range of assumptions and at least the same power for a noninferiority margin for the proportion of cancers prevented by RRES of those prevented by RRSO. Estimands based on incidence ratios had an infeasible sample size. CONCLUSIONS AND RELEVANCE: In this comparative effectiveness study of UK BRCA carriers, the estimand differed from other ongoing clinical effectiveness studies of RRES and DO. Advantages include direct use of expected risk at baseline (unknown at design stage), easier interpretation across cohorts than absolute risk differences, and providing a feasible recruitment target for PROTECTOR to evaluate clinical effectiveness.

Humans↗
PubMed2024

Ovarian tumor cells gain competitive advantage by actively reducing the cellular fitness of microenvironment cells.

Cell competition and fitness comparison between cancer and tumor microenvironment (TME) cells determine oncogenic fate. Our previous study established a role for human Flower isoforms as fitness fingerprints, where the expression of Flower Win isoforms in tumor cells leads to growth advantage over TME cells expressing Lose isoforms. Here we demonstrate that the expression of Flower Lose and reduced microenvironment fitness is not a pre-existing condition but, rather, a cancer-induced phenomenon. Cancer cells actively reduce TME fitness by the exosome-mediated release of a cancer-specific long non-coding RNA, Tu-Stroma, which controls the splicing of the Flower gene in the TME cells and expression of Flower Lose isoform, which leads to reduced fitness status. This mechanism controls cancer growth, metastasis and host survival in ovarian cancer. Targeting Flower protein with humanized monoclonal antibody (mAb) in mice significantly reduces cancer growth and metastasis and improves survival. Pre-treatment with Flower mAb protects intraperitoneal organs from developing lesions despite the presence of aggressive tumor cells.

Female↗
PubMed2006

The effect of telephone versus print tailoring for mammography adherence.

OBJECTIVE: The purpose of this intervention was to increase mammography adherence in women who had not had a mammogram in the last 15 months. METHODS: A prospective randomized intervention trial used four groups: (1) usual care, (2) tailored telephone counseling, (3) tailored print, (4) tailored telephone counseling and print. Participants included a total of 1244 women from two sites-a general medicine clinic setting serving predominately low-income clientele and a Health Maintenance Organization (HMO). Computer-tailored interventions addressed each woman's perceived risk of breast cancer, benefits and/or barriers and self-efficacy related to mammography screening comparing delivery by telephone and mail. RESULTS: Compared to usual care all intervention groups increased mammography adherence significantly (odds ratio 1.60-1.91) when the entire sample was included. CONCLUSIONS: All interventions groups demonstrated efficacy in increasing mammography adherence as compared to a usual care group. When the intervention analysis considered baseline stage, pre contemplators (women who did not intend to get a mammogram) did not significantly increase in mammography adherence as compared to usual care. PRACTICE IMPLICATIONS: Women who are in pre contemplation stage may need a more intensive intervention.

Computer-Assisted Instruction↗
PubMed2006

Cancer survivors information seeking behaviors: a comparison of survivors who do and do not seek information about cancer.

OBJECTIVE: To examine the cancer information seeking behaviors and preferences of cancer survivors. METHODS: This cross-sectional study used the National Cancer Institute's 2003 Health Information National Trends Survey data to evaluate 619 cancer survivors. RESULTS: Two-thirds (67.5%, n = 418) of the survivors sought cancer information (InfoSeek) and 32.5% (n = 201) did not (NoInfoSeek). Significant predictors of cancer information seeking included age (less than 65), gender (female), income (>US$ 25,000/year), and having a regular health care provider (HCP). CONCLUSION: Not all survivors actively look for cancer information. Although most survivors prefer receiving cancer information from their HCP, many turn to a variety of other sources, primarily the Internet. PRACTICE IMPLICATIONS: HCPs should periodically assess information seeking behaviors and preferences of cancer survivors and actively refer patients to the Internet as an extension of and enhancement to their patient interactions. Credible and useful websites could be identified and recommended by the HCP as a means to address some of the barriers identified by survivors.

Age Factors↗
PubMed2006

Tailored interventions for screening mammography among a sample of initially non-adherent women: when is a booster dose important?

OBJECTIVE: To assess added value of a booster dose of a tailored mammography intervention. METHODS: Participants, non-adherent at baseline, were randomly assigned to usual care or one of three tailored interventions. Intervention group members (n=657) were further randomly assigned to receive/not receive a booster intervention dose. Electronic record mammography data were collected following initial intervention and at 6 and 15 months post-booster. RESULTS: Booster had no effect among women not screened after first intervention dose (n=337). Among women screened after initial dose (n=320), booster predicted re-screening at 6 but not 15 months. A boosterxrace interaction showed a booster effect at 6 months for African Americans (OR=4.66, p=.0005) but not Caucasians (OR=0.74, p=.44). CONCLUSIONS: Findings suggest if a first-dose intervention does not facilitate screening, neither will a booster dose. However, among women for whom a first dose is effective, boosters can facilitate timely repeat adherence, especially among African Americans. At 6 months booster recipients were less likely to be off-schedule but, by 15 months, the groups were similar. PRACTICE IMPLICATIONS: Boosters may effect when, but not whether, women continue screening.

Black or African American↗
PubMed2006

Screening for ovarian cancer.

The efficacy of ovarian cancer screening remains to be proven. Advances in ultrasound and tumor marker technology, combined with complex statistical analysis have facilitated 2 large ongoing randomized controlled trials of screening which are powered to determine the impact on mortality. Serum proteomics seems to be a promising area for biomarker discovery, but requires more rigorous validation before it can be used in clinical trials. Current screening tests, clinical trials in the general and high-risk populations, screening acceptability and costs are reviewed in this article.

Biomarkers, Tumor↗
PubMed2006

The value of ovarian cancer screening.

Ovarian cancer is the commonest cause of death from a gynaecological malignancy. Diagnosis of the disease at an early stage is associated with significantly improved survival rate. This suggests that screening may impact on disease mortality. This review addresses the current methods of screening, the ongoing trials and future of screening for ovarian cancer.

CA-125 Antigen↗
PubMed2005

Prospective study using the risk of ovarian cancer algorithm to screen for ovarian cancer.

PURPOSE: To evaluate prevalence screening in the first prospective trial of a new ovarian cancer screening (OCS) strategy (risk of ovarian cancer or ROC algorithm) on the basis of age and CA125 profile. PATIENTS AND METHODS: Postmenopausal women, > or = 50 years were randomly assigned to a control group or screen group. Screening involved serum CA125, interpreted using the ROC algorithm. Participants with normal results returned to annual screening; those with intermediate results had repeat CA125 testing; and those with elevated values underwent transvaginal ultrasound (TVS). Women with abnormal or persistently equivocal TVS were referred for a gynecologic opinion. RESULTS: Thirteen thousand five hundred eighty-two women were recruited. Of 6,682 women randomly assigned to screening, 6,532 women underwent the first screen. After the initial CA125, 5,213 women were classified as normal risk, 91 women elevated, and 1,228 women intermediate. On repeat CA125 testing of the latter, a further 53 women were classified as elevated risk. All 144 women with elevated risk had TVS. Sixteen women underwent surgery. Eleven women had benign pathology; one woman had ovarian recurrence of breast cancer; one woman had borderline; and three women had primary invasive epithelial ovarian cancer (EOC). The specificity and positive predictive value (PPV) for primary invasive EOC were 99.8% (95% CI, 99.7 to 99.9) and 19% (95% CI, 4.1 to 45.6), respectively. CONCLUSION: An OCS strategy using the ROC algorithm is feasible and can achieve high specificity and PPV in postmenopausal women. It is being used in the United Kingdom Collaborative Trial of Ovarian Cancer Screening and in the United States in both the Cancer Genetics Network and the Gynecology Oncology Group trials of high-risk women.

Algorithms↗
PubMed2005

Breast and cervical cancer screening practices and inventions among Chinese, Japanese, and Vietnamese Americans.

PURPOSE/OBJECTIVES: To review research on breast and cervical cancer screening practices among Chinese, Japanese, and Vietnamese Americans. DATA SOURCES: MEDLINE and the Cumulative Index to Nursing and Allied Health Literature databases. DATA SYNTHESIS: Of the 28 studies reviewed, 19 (68%) were descriptive and 9 (32%) were interventions. Instruments were developed or translated into the native language. Inconsistent operational definitions for positive facilitators and negative barriers made comparisons across studies difficult. CONCLUSIONS: Research about breast and cervical cancer screening is limited in these groups. All of the studies reviewed indicated low adherence to cancer screening guidelines. Some interventions showed promising results. Poor awareness about cancer was reported; positive facilitators and negative barriers were identified. IMPLICATIONS FOR NURSING: The rapidly increasing number of Asian Americans in the United States underscores the need for further research in this area. Future studies should focus on each population as a disaggregated subgroup. Cancer control interventions should be culturally competent.

Adult↗
PubMed2005

Development of a self-efficacy scale for mammography.

Mammography screening has been demonstrated to decrease mortality from breast cancer. Although adherence rates have increased, there is still a need to increase annual screening. Self-efficacy is a construct that has been found useful in predicting behaviors. Measurement of self-efficacy needs to be specific to the behavior and to have good validity and reliability. The purpose of this study is to describe development of a self-efficacy instrument to measure confidence in obtaining a mammogram. Bandura's model guided item development. Construct validity was measured using confirmatory factor analysis and logistic regression. Cronbach alpha was used to test internal consistency reliability. A Cronbach alpha coefficient of .87 was obtained. The mammography self-efficacy scale evidenced content and construct validity.

Aged↗
PubMed2004

Progress and challenges in screening for early detection of ovarian cancer.

Ovarian cancer is characterize by few early symptoms, presentation at an advanced stage, and poor survival. As a result, it is the most frequent cause of death from gynecological cancer. During the last decade, a research effort has been directed toward improving outcomes for ovarian cancer by screening for preclinical, early stage disease using both imaging techniques and serum markers. Numerous biomarkers have shown potential in samples from clinically diagnosed ovarian cancer patients, but few have been thoroughly assessed in preclinical disease and screening. The most thoroughly investigated biomarker in ovarian cancer screening is CA125. Prospective studies have demonstrated that both CA125 and transvaginal ultrasound can detect a significant proportion of preclinical ovarian cancers, and refinements in interpretation of results have improved sensitivity and reduced the false-positive rate of screening. There is preliminary evidence that screening can improve survival, but the impact of screening on mortality from ovarian cancer is still unclear. Prospective studies of screening are in progress in both the general population and high-risk population, including the United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS), a randomized trial involving 200,000 postmenopausal women designed to document the impact of screening on mortality. Recent advances in technology for the study of the serum proteome offer exciting opportunities for the identification of novel biomarkers or patterns of markers that will have greater sensitivity and lead time for preclinical disease than CA125. Considerable interest and controversy has been generated by initial results utilizing surface-enhanced laser desorption/ionization (SELDI) in ovarian cancer. There are challenging issues related to the design of studies to evaluate SELDI and other proteomic technology, as well as the reproducibility, sensitivity, and specificity of this new technology. Large serum banks such as that assembled in UKCTOCS, which contain preclinical samples from patients who later developed ovarian cancer and other disorders, provide a unique resource for carefully designed studies of proteomic technology. There is a sound basis for optimism that further developments in serum proteomic analysis will provide powerful methods for screening in ovarian cancer and many other diseases.

Biomarkers, Tumor↗
PubMed2004

A cost-effectiveness comparison of three tailored interventions to increase mammography screening.

BACKGROUND: Mammography is the primary method used for breast cancer screening. However, adherence to recommended screening practices is still below acceptable levels. This study examined the cost-effectiveness of three combinations of tailored telephone and mailed intervention strategies for increasing adherence to mammography. METHODS: There were 1044 participants who were randomly assigned to one of four groups. A logistic regression model with adherence as the dependent variable and group as the independent variable was used to test for significant differences, and a ratio of cost/improvement in mammogram adherence evaluated the cost-effectiveness. RESULTS: All three of the interventions (tailored telephone, tailored mail, and tailored telephone and mail) had significantly better adherence rates compared with the control group (usual care). However, when also considering costs, one emerged as the superior strategy. The cost-effectiveness ratios for the three interventions show that the tailored mail (letter) was the most cost-effective strategy, achieving 43.3% mammography adherence at a marginal cost of dollar 0.39 per 1% increase in women screened. The tailored mail plus telephone achieved greater adherence (49.4%), but at a higher cost (dollar 0.56 per 1% increase in women screened). CONCLUSIONS: A tailored mail reminder is an effective and economical intervention to increase mammography adherence. Future research should confirm this finding and address its applicability to practice in other settings.

Adult↗
PubMed2004

A breast cancer fear scale: psychometric development.

Fear of breast cancer has been inversely associated with participation in screening. However, investigators have generally used only one item or global scales to measure fear. This report describes development of a fear scale specific to breast cancer. Data from a large study involving mammography adherence were used to test the breast cancer fear scale for validity and reliability. Construct validity was verified through factor analysis and regression analysis predicting mammography. All items loaded on a single factor and theoretical relationships were verified by linear and logistic regression. The Cronbach alpha for the scale was.91.

Aged↗
PubMed2003

Calculation of the risk of ovarian cancer from serial CA-125 values for preclinical detection in postmenopausal women.

PURPOSE: Previous studies of CA-125 levels from screening trials for ovarian cancer have indicated that serial CA-125 levels may identify cases better than a fixed CA-125 cutoff. We conducted a study to assess the screening performance of the risk of ovarian cancer calculation based on serial CA-125 levels from prospectively collected serum samples compared with a fixed CA-125 cutoff. PATIENTS AND METHODS: The calculation was applied to data from a prospective trial of screening for ovarian cancer involving 22,000 postmenopausal women older than 45 years. The analysis was performed using 33,621 CA-125 results from 9,233 women for whom two or more serial samples were available. All serum samples from the patients with ovarian cancer were obtained before clinical detection. Sensitivity and specificity levels for preclinical detection of index cancers were calculated for various cutoffs for the risk and a single CA-125 measurement, and receiver operator curves were constructed. RESULTS: The risk calculation significantly improved the area under the curve from 84% to 93% compared with a fixed cutoff for CA-125 (P =.01). For a target specificity of 98%, the risk achieved a sensitivity of 86% for preclinical detection of ovarian cancer, whereas CA-125 achieved a sensitivity of 62%. The estimates of performance are unbiased, because the risk calculation was derived independent of the data from this trial. CONCLUSION: These results provide the first evidence that preclinical detection of ovarian cancer using serial CA-125 levels interpreted with the risk calculation significantly improves screening performance compared with a fixed cutoff for CA-125. The results justify the incorporation of the risk calculation in a prospective, randomized, controlled trial.

Area Under Curve↗
PubMed2003

Comparison of tailored interventions to increase mammography screening in nonadherent older women.

BACKGROUND: Recent increases in mammography use have led to a decrease in mortality from breast cancer. METHODS: Building on the Health Belief Model, the Transtheoretical Model, and past effectiveness of tailored interventions, we conducted a prospective randomized trial (n = 773) to test the efficacy on mammography adherence of tailored interventions delivered by five different methods, i.e., telephone counseling, in-person counseling, physician letter, and combinations of telephone with letter and in-person with letter. RESULTS: All five interventions increased mammography adherence significantly relative to usual care (odds ratios, 1.93 to 3.55) at 6 months post intervention. The combination of in-person with physician letter was significantly more effective than telephone alone or letter alone. Women thinking about getting a mammogram at baseline were more likely to be adherent by 6 months; even those in usual care achieved 48% adherence compared with 50-70% in the intervention groups. In contrast, women not thinking about getting a mammogram needed the interventions to increase their adherence from 13% to over 30%. CONCLUSIONS: All five interventions were effective at increasing mammography adherence. Women not thinking about getting a mammogram were most likely to benefit from these tailored interventions while other women might need less intensive interventions.

Breast Neoplasms↗