Screening mammography frequency following dense breast notification among a predominantly Hispanic/Latina screening cohort.

PURPOSE: Nationally legislated dense breast notification (DBN) informs women of their breast density (BD) and the impact of BD on breast cancer risk and detection, but consequences for screening participation are unclear. We evaluated the association of DBN in New York State (NYS) with subsequent screening mammography in a largely Hispanic/Latina cohort. METHODS: Women aged 40-60 were surveyed in their preferred language (33% English, 67% Spanish) during screening mammography from 2016 to 2018. We used clinical BD classification from mammography records from 2013 (NYS DBN enactment) through enrollment (baseline) to create a 6-category variable capturing prior and new DBN receipt (sent only after clinically dense mammograms). We used this variable to compare the number of subsequent mammograms (0, 1, ≥ 2) from 10 to 30 months after baseline using ordinal logistic regression. RESULTS: In a sample of 728 women (78% foreign-born, 72% Hispanic, 46% high school education or less), first-time screeners and women who received DBN for the first time after prior non-dense mammograms had significantly fewer screening mammograms within 30 months of baseline (Odds Ratios range: 0.33 (95% Confidence Interval (CI) 0.12-0.85) to 0.38 (95% CI 0.17-0.82)) compared to women with prior mammography but no DBN. There were no differences in subsequent mammogram frequency between women with multiple DBN and those who never received DBN. Findings were consistent across age, language, health literacy, and education groups. CONCLUSION: Women receiving their first DBN after previous non-dense mammograms have lower mammography participation within 2.5 years. DBN has limited influence on screening participation of first-time screeners and those with persistent dense mammograms.

Scientific uncertainty and perceived mammography benefits in women screened for breast cancer.

PURPOSE: Personal aversion to scientific uncertainty may influence how women perceive the benefits of mammography, a breast cancer screening practice with conflicting scientific opinions and guidelines. Such associations may even exist among women who participate in screening. METHODS: We evaluated the distribution of aversion to ambiguous medical information (AA-Med), using a 6-item scale capturing the level of agreement with statements about obtaining a cancer screening test with conflicting medical recommendations in 665 women (aged 40-60 years; 79.5% Hispanic) recruited during screening mammography appointments in New York City. We assessed the association of AA-Med with perceptions of benefits of mammography (breast cancer mortality reduction, worry reduction, early detection, treatment improvement) using multivariable logistic regression. RESULTS: Over a quarter of participants expressed negative reactions to medical ambiguity about a cancer screening test (e.g., fear, lower trust in experts), but a majority endorsed intention to undergo screening. AA-Med was higher in women who were U.S.-born, non-Hispanic black, and had marginal to adequate health literacy, but there were no differences by clinical factors or screening experiences (e.g., family history, prior breast biopsy). Women with higher AA-Med were more likely to perceive treatment benefits from mammography (OR = 1.37, 95% CI = 0.99-1.90), but AA-Med was not associated with other perceived mammography benefits. CONCLUSIONS: Aversion to uncertainty regarding cancer screening varies by sociodemographic characteristics but has limited associations with perceived mammography benefits in women who already participate in screening.

Breast cancer worry, uncertainty, and perceived risk following breast density notification in a longitudinal mammography screening cohort.

BACKGROUND: Dense breast notification (DBN) legislation aims to increase a woman's awareness of her personal breast density and the implications of having dense breasts for breast cancer detection and risk. This information may adversely affect women's breast cancer worry, perceptions of risk, and uncertainty about screening, which may persist over time or vary by sociodemographic factors. We examined short- and long-term psychological responses to DBN and awareness of breast density (BD). METHODS: In a predominantly Hispanic New York City screening cohort (63% Spanish-speaking), ages 40-60 years, we assessed breast cancer worry, perceived breast cancer risk, and uncertainties about breast cancer risk and screening choices, in short (1-3 months)- and long-term (9-18 months) surveys following the enrollment screening mammogram (between 2016 and 2018). We compared psychological responses by women's dense breast status (as a proxy for DBN receipt) and BD awareness and examined multiplicative interaction by education, health literacy, nativity, and preferred interview language. RESULTS: In multivariable models using short-term surveys, BD awareness was associated with increased perceived risk (odds ratio (OR) 2.27, 95% confidence interval (CI) 0.99, 5.20 for high, OR 2.19, 95% CI 1.34, 3.58 for moderate, vs. low risk) in the overall sample, and with increased uncertainty about risk (OR 1.97 per 1-unit increase, 95% CI 1.15, 3.39) and uncertainty about screening choices (OR 1.73 per 1-unit increase, 95% CI 1.01, 2.9) in Spanish-speaking women. DBN was associated with decreased perceived risk among women with at least some college education (OR 0.32, 95% CI 0.11, 0.89, for high, OR 0.50, 95% CI 0.29, 0.89, for moderate vs. low risk), while those with a high school education or less experienced an increase (OR 3.01, 95% CI 1.05, 8.67 high vs. low risk). There were no associations observed between DBN or BD awareness and short-term breast cancer worry, nor with any psychological outcomes at long-term surveys. CONCLUSIONS: Associations of BD awareness and notification with breast cancer-related psychological outcomes were limited to short-term increases in perceived breast cancer risk dependent on educational attainment, and increases in uncertainty around breast cancer risk and screening choices among Spanish-speaking women.

"It's something I'll do until I die": A qualitative examination into why older women in the U.S. continue screening mammography.

BACKGROUND: Professional guidelines in the U.S. do not recommend routine screening mammography for women ≥75 years with limited life expectancy and/or poor health. Yet, routine mammography remains widely used in older women. We examined older women's experiences, beliefs, and opinions about screening mammography in relation to aging and health. METHODS: We performed thematic analysis of transcribed semi-structured interviews with 19 women who had a recent screening visit at a mammography clinic in New York City (average age: 75 years, 63% Hispanic, 53% ≤high school education). RESULTS: Three main themes emerged: (1) older women typically perceive mammograms as a positive, beneficial, and routine component of care; (2) participation in routine mammography is reinforced by factors at interpersonal, provider, and healthcare system levels; and (3) older women do not endorse discontinuation of screening mammography due to advancing age or poor health, but some may be receptive to reducing screening frequency. Only a few older women reported having discussed mammography cessation or the potential harms of screening with their providers. A few women reported they would insist on receiving mammography even without a provider recommendation. CONCLUSIONS: Older women's positive experiences and views, as well as multilevel and frequently automated cues toward mammography are important drivers of routine screening in older women. These findings suggest a need for synergistic patient, provider, and system level strategies to reduce mammography overuse in older women.

Current regular aspirin use and mammographic breast density: a cross-sectional analysis considering concurrent statin and metformin use.

PURPOSE: The nonsteroidal anti-inflammatory drug aspirin is an agent of interest for breast cancer prevention. However, it is unclear if aspirin affects mammographic breast density (MBD), a marker of elevated breast cancer risk, particularly in the context of concurrent use of medications indicated for common cardiometabolic conditions, which may also be associated with MBD. METHODS: We used data from the New York Mammographic Density Study for 770 women age 40-60 years old with no history of breast cancer. We evaluated the association between current regular aspirin use and MBD, using linear regression for continuous measures of absolute and percent dense areas and absolute non-dense area, adjusted for body mass index (BMI), sociodemographic and reproductive factors, and use of statins and metformin. We assessed effect modification by BMI and reproductive factors. RESULTS: After adjustment for co-medication, current regular aspirin use was only positively associated with non-dense area (ß = 18.1, 95% CI: 6.7, 29.5). Effect modification by BMI and parity showed current aspirin use to only be associated with larger non-dense area among women with a BMI ≥ 30 (ß = 28.2, 95% CI: 10.8, 45.7), and with lower percent density among parous women (ß = -3.3, 95% CI: -6.4, -0.3). CONCLUSIONS: Independent of co-medication use, current regular aspirin users had greater non-dense area with stronger estimates for women with higher BMI. We found limited support for an association between current aspirin use and mammographically dense breast tissue among parous women.

A mixed-methods study of multi-level factors influencing mammography overuse among an older ethnically diverse screening population: implications for de-implementation.

BACKGROUND: There is growing concern that routine mammography screening is overused among older women. Successful and equitable de-implementation of mammography will require a multi-level understanding of the factors contributing to mammography overuse. METHODS: This explanatory, sequential, mixed-methods study collected survey data (n= 52, 73.1% Hispanic, 73.1% Spanish-speaking) from women ≥70 years of age at the time of screening mammography, followed by semi-structured interviews with a subset of older women completing the survey (n=19, 63.2% Hispanic, 63.2% Spanish-speaking) and providers (n=5, 4 primary care, 1 obstetrics and gynecology) to better understand multi-level factors influencing mammography overuse and inform potential de-implementation strategies. We conducted a descriptive analysis of survey data and content analysis of qualitative interview data. Survey and interview data were examined separately, compared, integrated, and organized according to Norton and Chambers Continuum of Factors Influencing De-Implementation Process. RESULTS: Survey findings show that 87.2% of older women believe it is important to plan for an annual mammogram, 80.8% received a provider recommendation, and 78.9% received a reminder in the last 12 months to schedule a mammogram. Per interviews with older women, the majority were unaware of or did not perceive to have experienced overuse and intended to continue mammography screening. Findings from interviews with older women and providers suggest that there are multiple opportunities for older women to obtain a mammogram. Per provider interviews, almost all reported that reducing overuse was not viewed as a priority by the system or other providers. Providers also discussed that variation in mammography screening practices across providers, fear of malpractice, and monetary incentives may contribute to overscreening. Providers identified potential strategies to reduce overscreening including patient and provider education around harms of screening, leveraging the electronic health record to identify women who may receive less health benefit from screening, customizing system-generated reminder letters, and organizing workgroups to develop standard processes of care around mammography screening. CONCLUSIONS: Multi-level factors contributing to mammography overuse are dynamic, interconnected, and reinforced. To ensure equitable de-implementation, there is a need for more refined and empirical testing of theories, models, and frameworks for de-implementation with a strong patient-level component that considers the interplay between multilevel factors and the larger care delivery process.

Breast Density Awareness and Knowledge in a Mammography Screening Cohort of Predominantly Hispanic Women: Does Breast Density Notification Matter?

BACKGROUND: New York State law mandates that women with dense breasts receive a written notification of their breast density (BD) and its implications, but data on the impact of dense breast notification (DBN) on BD awareness and knowledge in diverse populations remain limited. METHODS: Between 2016 and 2018, we collected survey and mammographic data from 666 women undergoing screening mammography in New York City (ages 40-60, 80% Hispanic, 69% Spanish-speaking) to examine the impact of prior DBN on BD awareness by sociodemographic and breast cancer risk factors, and describe BD knowledge by sources of information. RESULTS: Only 24.8% of the overall sample and 34.9% of women receiving DBN had BD awareness. In multivariable models adjusting for DBN, awareness was significantly lower in women who were Spanish-speaking [OR, 0.16; 95% confidence interval (CI), 0.09-0.30 vs. English speakers], were foreign-born (OR, 0.31; 95% CI, 0.16-0.58 vs. U.S.-born), and had lower educational attainment (e.g., high school degree or less; OR, 0.14; 95% CI, 0.08-0.26 vs. college or higher degree). Women receiving DBN were more likely to be aware of BD (OR, 2.61; 95% CI, 1.59-4.27) but not more knowledgeable about the impact of BD on breast cancer risk and detection. However, women reporting additional communication about their BD showed greater knowledge in these areas. CONCLUSIONS: DBN increases BD awareness disproportionately across sociodemographic groups. IMPACT: Efforts to improve communication of DBN must focus on addressing barriers in lower socioeconomic and racially and ethnically diverse women, including educational and language barriers.

Independent and joint cross-sectional associations of statin and metformin use with mammographic breast density.

BACKGROUND: Well-tolerated and commonly used medications are increasingly assessed for reducing breast cancer risk. These include metformin and statins, both linked to reduced hormone availability and cell proliferation or growth and sometimes prescribed concurrently. We investigated independent and joint associations of these medications with mammographic breast density (MBD), a useful biomarker for the effect of chemopreventive agents on breast cancer risk. METHODS: Using data from a cross-sectional study of 770 women (78% Hispanic, aged 40-61 years, in a mammography cohort with high cardiometabolic burden), we examined the association of self-reported "ever" use of statins and metformin with MBD measured via clinical Breast Imaging Reporting and Data System (BI-RADS) density classifications (relative risk regression) and continuous semi-automated percent and size of dense area (Cumulus) (linear regression), adjusted for age, body mass index, education, race, menopausal status, age at first birth, and insulin use. RESULTS: We observed high statin (27%), metformin (13%), and combination (9%) use, and most participants were overweight/obese (83%) and parous (87%). Statin use was associated with a lower likelihood of high density BI-RADS (RR = 0.60, 95% CI = 0.45 to 0.80), percent dense area (PD) (ß = - 6.56, 95% CI = - 9.05 to - 4.06), and dense area (DA) (ß = - 9.05, 95% CI = - 14.89 to - 3.22). Metformin use was associated with lower PD and higher non-dense area (NDA), but associations were attenuated by co-medication with statins. Compared to non-use of either medication, statin use alone or with metformin were associated with lower PD and DA (e.g., ß = - 6.86, 95% CI: - 9.67, - 4.05 and ß = - 7.07, 95% CI: - 10.97, - 3.17, respectively, for PD) and higher NDA (ß = 25.05, 95% CI: 14.06, 36.03; ß = 29.76, 95% CI: 14.55, 44.96, respectively). CONCLUSIONS: Statin use was consistently associated with lower MBD, measured both through clinical radiologist assessment and continuous relative and absolute measures, including dense area. Metformin use was associated with lower PD and higher NDA, but this may be driven by co-medication with statins. These results support that statins may lower MBD but need confirmation with prospective and clinical data to distinguish the results of medication use from that of disease.

Idiopathic Pulmonary Fibrosis and Lung Cancer. A Systematic Review and Meta-analysis.

Rationale: The association between idiopathic pulmonary fibrosis (IPF) and lung cancer has been previously reported. However, there is the potential for significant confounding by age and smoking, and an accurate summary risk estimate has not been previously ascertained.Objectives: To determine the risk and burden of lung cancer in patients with IPF, accounting for known confounders.Methods: We conducted a comprehensive literature search of MEDLINE, EMBASE, and SCOPUS databases and used the Newcastle Ottawa criteria to assess study quality. We then assessed the quality of ascertainment of IPF cases based on modern consensus criteria. Data that relied on administrative claims or autopsies were excluded. We calculated summary risk estimates using a random effects model.Results: Twenty-five cohort studies were included in the final analysis. The estimated adjusted incidence rate ratio from two studies was 6.42 (95% confidence interval [CI], 3.21-9.62) and accounted for age, sex, and smoking. The summary incidence rate from 11 studies was 2.07 per 100 person-years (95% CI, 1.46-2.67), and the summary mortality rate was 1.06 per 100 person-years (95% CI, 0.62-1.51) obtained from three studies. The summary prevalence from 11 studies was 13.74% (95% CI, 10.17-17.30), and the proportion of deaths attributable to lung cancer was 10.20 (95% CI, 8.52-11.87) and was obtained from nine studies.Conclusions: IPF is an increased independent risk factor for lung cancer, even after accounting for smoking. Further well-designed studies using modern consensus criteria are needed to explore mechanisms of this association.

Candida parapsilosis fat storage-inducing transmembrane (FIT) protein 2 regulates lipid droplet formation and impacts virulence.

Neutral lipid storage in lipid droplets (LDs) is a conserved process across diverse species. Although significant attention has focused on LDs in the biology of obesity, diabetes, and atherosclerosis, there is limited information on the role of LDs in pathogenic fungi. We have disrupted the Fat storage-Inducing Transmembrane (FIT) protein 2 genes of the emerging pathogenic fungus Candida parapsilosis and demonstrated that LD formation is significantly reduced in the mutant cells. Disruption of FIT2 genes also reduced accumulation of triacylglycerols. The production of other lipids such as phospholipids and steryl esters were also affected in the mutant strain. Inhibition of de novo fatty acid biosynthesis by triclosan in the FIT2 disruptants reduced fungal growth in rich medium YPD, indicating that TAGs or fatty acids from the LDs could be important for cell proliferation. FIT2 disruption was associated with enhanced sensitivity to oxidative stress. Furthermore, we showed that FIT2 deletion yeast cells were significantly attenuated in murine infection models, suggesting an involvement of LDs in the pathobiology of the fungus.

Acetylsalicylic acid (aspirin) reduces damage to reconstituted human tissues infected with Candida species by inhibiting extracellular fungal lipases.

A reconstituted human tissue model was used to mimic Candida albicans and Candida parapsilosis infection in order to investigate the protective effects of acetylsalicylic acid (aspirin, ASA). We found that therapeutic concentrations of ASA reduced tissue damage in the in vitro infection model. We further evaluated the lipase inhibitory effects of ASA by investigating the growth of C. albicans, C. parapsilosis and C. parapsilosis lipase negative (Deltacplip1-2/Deltacplip1-2) mutants in a lipid rich minimal medium supplemented with olive oil and found that a therapeutic concentration of ASA inhibited the growth of wild type fungi. The lipase inhibitors quinine and ebelactone B were also shown to reduce growth and protect against tissue damage from Candida species, respectively. A lipolytic activity assay also showed that therapeutic concentrations of ASA inhibited C. antarctica and C. cylindracea purified lipases obtained through a commercial kit. The relationship between ASA and lipase was characterized through a computed structural model of the Lipase-2 protein from C. parapsilosis in complex with ASA. The results suggest that development of inhibitors of fungal lipases could result in broad-spectrum therapeutics, especially since fungal lipases are not homologous to their human analogues.