Breast cancer screening attitudes, beliefs, and behaviors of Zuni Pueblo women: identifying cornerstones for building effective mammogram screening intervention programs.

PURPOSE: Breast cancer is the leading form of cancer and has the second highest mortality rate of cancers for American Indian/Alaska Native (AI/AN) women. Early screening is critical. This study examines the breast cancer-related knowledge, beliefs, and behaviors of Zuni women in the Southwest United States (U.S.). METHODS: In 2020 and 2021, a survey was administered to better understand cancer screening patterns in Zuni Pueblo; 110 women from 50 to 75 years of age were recruited to respond to the breast cancer screening portion. Inclusion criteria included self-identifying as AI, a member of the Zuni tribe, or married to a Zuni tribal member, and meeting the age and gender requirements. Descriptive statistics and bivariate analyses were conducted examining the associations between measures of breast cancer knowledge, beliefs, and behaviors and breast cancer screening status (never, ever/non-compliant, and ever/compliant). RESULTS: Of survey participants, 47.3% have had a breast cancer screening and are up-to-date, 39.1% have had a screening in the past but are not up-to-date, and 13.6% have never been screened. Age was the only statistically significant socioeconomic predictor of breast cancer screening; the median (interquartile range) ages of each group are 62 (54, 68) ever/compliant, 56 (54, 68) ever/non-compliant, and 53 (51, 55) never (p-value < 0.001). Significant differences by health status and access to medical care include having a regular health care provider and going to see a provider for routine check-ups. The survey also shows differences in knowledge about breast cancer risk factors, beliefs, and behaviors. Women across all three screening statuses reported that they would get screened if encouraged by a health care provider. CONCLUSION: While survey respondents report a relatively high rate of ever having had a breast cancer screening, less than half are compliant with screening guidelines, which shows there is an opportunity to improve breast cancer screening rates. With culturally tailored interventions, providers have the potential to improve breast cancer screening for Zuni women.

Peritoneal Dialysis Technique Survival: A Cohort Study.

RATIONALE & OBJECTIVE: Reasons for transfer from peritoneal dialysis (PD) to hemodialysis (HD) remain incompletely understood. Among incident and prevalent patients receiving PD, we evaluated the association of clinical factors, including prior treatment with HD, with PD technique survival. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Adults who initiated PD at a Dialysis Clinic, Inc (DCI) outpatient facility between January 1, 2010, and September 30, 2019. EXPOSURE: The primary exposure of interest was timing of PD start, categorized as PD-first, PD-early, or PD-late. Other covariates included demographics, clinical characteristics, and routine laboratory results. OUTCOME: Modality switch from PD to HD sustained for more than 90 days. ANALYTICAL APPROACH: Multivariable Fine-Gray models with competing risks and time-varying covariates, stratified at 9 months to account for lack of proportionality. RESULTS: Among 5,224 patients who initiated PD at a DCI facility, 3,174 initiated dialysis with PD ("PD-first"), 942 transitioned from HD to PD within 90 days ("PD-early"), and 1,108 transitioned beyond 90 days ("PD-late"); 1,472 (28%) subsequently transferred from PD to HD. The PD-early and PD-late patients had a higher risk of transfer to HD as compared with PD-first patients (in the first 9 months: adjusted hazard ratio [AHR], 1.51 [95% CI, 1.17-1.96] and 2.41 [95% CI, 1.94-3.00], respectively; and after 9 months: AHR, 1.16 [95% CI, 0.99-1.35] and AHR, 1.43 [95% CI, 1.24-1.65], respectively). More peritonitis episodes, fewer home visits, lower serum albumin levels, lower residual kidney function, and lower peritoneal clearance calculated with weekly Kt/V were additional risk factors for PD-to-HD transfer. LIMITATIONS: Missing data on dialysis adequacy and residual kidney function, confounded by short PD technique survival. CONCLUSIONS: Initiating dialysis with PD is associated with greater PD technique survival, though many of those who initiate PD-late in their dialysis course still experience substantial time on PD. Peritonitis, lower serum albumin, and lower Kt/V are risk factors for PD-to-HD transfer that may be amenable to intervention. PLAIN-LANGUAGE SUMMARY: Peritoneal dialysis (PD) is an important kidney replacement modality with several potential advantages compared with in-center hemodialysis (HD). However, a substantial number of patients transfer to in-center HD early on, without having experienced the quality-of-life and other benefits that come with sustained maintenance of PD. Using retrospective data from a midsize national dialysis provider, we found that initiating dialysis with PD is associated with longer maintenance of PD, compared with initiating dialysis with HD and a later switch to PD. However, many of those who initiate PD-late in their dialysis course still experience substantial time on PD. Peritonitis, lower serum albumin, and lower small protein removal are other risk factors for PD-to-HD transfer that may be amenable to intervention.

A pilot randomized, placebo-controlled, double-blind study of omega-3 fatty acids to prevent paclitaxel-associated acute pain syndrome in breast cancer patients: Alliance A22_Pilot2.

PURPOSE: Paclitaxel is associated with an acute pain syndrome (P-APS- and chronic chemotherapy-induced peripheral neuropathy (CIPN). P-APS is associated with higher risk of CIPN. Omega-3 fatty acids have well-established anti-inflammatory and neuroprotective properties. The primary purpose of this pilot study was to assess whether omega-3 fatty acids could decrease P-APS and thus CIPN. METHODS: Patients scheduled to receive weekly paclitaxel for breast cancer were randomized to receive 4 g of omega-3 acid ethyl esters (Lovaza) or placebo, beginning 1 week prior and continued until paclitaxel was stopped. Patients completed acute pain questionnaires at baseline, daily after each treatment, and 1 month after completion of therapy. RESULTS: Sixty patients (49 evaluable) were randomized to treatment versus placebo. Seventeen (68.0%) patients receiving the omega-3 fatty acids intervention experienced P-APS, compared to 15 (62.5%) of those receiving placebo during the first week of treatment (p = 0.77). Over the full 12-week study, 21 (84.0%) patients receiving the omega-3 fatty acid intervention experienced P-APS, compared to 21 (87.5%) of those receiving placebo (p = 1.0). Secondary outcomes suggested that those in the intervention arm used more over-the-counter analgesics (OR: 1.65, 95% CI: 0.72-3.78, p = 0.23), used more opiates (OR: 2.06, 95% CI: 0.55-7.75, p = 0.28), and experienced higher levels of CIPN (12.8, 95% CI: 7.6-19.4 vs. 8.4, 95% CI: 4.6-13.2, p = 0.21). CONCLUSIONS: The results of this pilot study do not support further study of the use of omega-3 fatty acids for the prevention of the P-APS and CIPN. TRIAL REGISTRATION: Number: NCT01821833.

Colorectal Cancer Screening Among Adults in Zuni Pueblo: Factors Associated with FOBT and Colonoscopy Utilization.

Although strategies to mitigate barriers to colorectal cancer (CRC) screening have proven successful in some parts of the US, few of these strategies have been studied in rural, American Indian communities that may exhibit unique culturally driven attitudes toward and knowledge of colorectal cancer and experience increased barriers to healthcare access. In this study, we describe the results of a survey among CRC screen-eligible members of Zuni Pueblo (N = 218) on an array of questions regarding CRC screening behaviors, knowledge, satisfaction with and access to healthcare services, social support for CRC screening, perceptions toward FOBT, and preference for evidence-based interventions or strategies for improving CRC screening rates. Results from the multivariable model suggest age, having a regular healthcare provider, and harboring fewer negative perceptions toward FOBT are key drivers of ever completing CRC screening. Respondents reported strong support for Community Guide-recommended interventions and strategies for increasing CRC screening for nearly all proposed interventions. Results confirm the need for multilevel, multicomponent interventions, with a particular focus on improving Zuni Pueblo community members' access to a regular source of care, improving knowledge of CRC risk factor, and addressing negative perceptions toward CRC screening. These results provide critical, community-specific insight into better understanding the drivers of low guideline-adherent screening rates and inform local healthcare providers and community leaders of context-specific strategies to improve CRC screening in Zuni Pueblo.

Health Literacy, Health Numeracy, and Cancer Screening Patterns in the Zuni Pueblo: Insights from and Limitations of "Standard" Questions.

American Indians experience disparities in cancer screening, stage at disease diagnoses, and 5-year cancer survival. This study investigates how health literacy and health numeracy may be linked to cancer screening behaviors of Zuni Pueblo members using a survey exploring screening behaviors related to breast, cervical, and colorectal cancers. As part of a larger community-based cancer prevention and control project, Zuni Health Initiative staff conducted surveys from October 2020 through April 2021 of 281 participants (men ages 50-75 and women ages 21-75) from the Zuni Pueblo. Bivariate and multivariable analyses investigated associations between health literacy/numeracy measures and cancer screening behaviors. Bivariate analyses showed some associations between distinct measures of health literacy/numeracy and colorectal cancer (CRC) screening, including both colonoscopy (health literacy) and fecal occult blood testing (FOBT) (health numeracy), as well as cervical cancer screening (health literacy). There were no statistically significant associations between health literacy/numeracy measures and mammogram screening for breast cancer. In multivariable analyses, there were no consistent patterns between health literacy/numeracy and screening for any cancer. There are some individual findings worth noting, such as statistically significant findings for health numeracy and FOBT (those reporting lower health numeracy were less likely to report FOBT). An important finding of this study is that questions used to assess health literacy/numeracy did not identify associations aligned with previous research. We reflect on the ways the "standard" questions may not be sufficiently tailored to the Zuni experience and may contribute to health equity barriers.

Cervical Cancer Knowledge and Screening Patterns in Zuni Pueblo Women in the Southwest United States.

American Indian women experience cervical cancer disparities, including later-stage diagnosis and a higher cervical cancer mortality rate. These disparities are interconnected and linked to cervical cancer screening disparities. Cervical cancer when identified early is highly treatable. Individual- and health system-level factors often contribute to gaps in cervical cancer screening. To better understand the source of these inequities experienced by American Indian women, specifically Zuni women, this paper examines how knowledge about cervical cancer and related risk factors is linked to cervical cancer screening for Zuni women using primary data gathered by the Zuni Health Initiative in 2020 and 2021. We find that of the women who completed the survey (n = 171), women with greater cervical cancer knowledge are statistically significantly more likely to have received cervical cancer screening. Closer examination of knowledge on the specific risk factors for cervical cancer provides evidence upon which to develop a cervical cancer education intervention.

Patient, provider, and nurse preferences of patient reported outcomes (PRO) and side effect management during cancer treatment of underrepresented racial and ethnic minority groups, rural and economically disadvantaged patients: a mixed methods study.

PURPOSE: The purpose of this study was to evaluate patient, oncologist and nurse perspectives on side effects and patient reported outcomes (PROs) with the question of how to optimize side effect management and PRO tools in this unique population. METHODS: This pilot study utilized a mixed method explanatory design. Patients receiving intravenous (IV) chemotherapy from June to August 2020 were surveyed about side effect burden and PRO system preferences. Providers and nurses (PN) completed complementary surveys. Semi-structured phone interviews were conducted among a subset of each group. RESULTS: Of 90 patient surveys collected; 51.1% minority, 35.6% rural, and 40.0% income < $30,000, 48% felt side effect management was a significant issue. All patients reported access to a communication device but 12.2% did not own a cell phone; 68% smart phone, 20% cell phone, 22% landline, 53% computer, and 39% tablet. Patients preferred a response to reported side effects within 0-3 h (73%) while only 29% of the 55 PN surveyed did (p < 0.0001). Interviews reinforced that side effect burden was a significant issue, the varied communication devices, and a PRO system could improve side effect management. CONCLUSION: In a non-White, rural and low-income patient population, 87.8% of patients reported owning a cell phone. Although all agreed side effect management was a prominent issue, expectations between patients and PN differed substantially. Qualitative data echoed the above and providing concrete suggestions to inform development of a PRO program and side effect mitigation strategies among a diverse patient population.

Autonomy and focus of attention in medical motor skills learning: a randomized experiment.

BACKGROUND: The 'OPTIMAL' (Optimizing Performance Through Intrinsic Motivation and Attention for Learning) theory of motor learning suggests that autonomy, external focus of attention, and perceived competence can improve learning of simple motor tasks. The authors hypothesized that enhanced (vs. routine) autonomy and external (vs. internal) focus of attention would improve first-try performance of two medical motor tasks. METHODS: The authors conducted a randomized two-by-two factorial design study with high school students as participants. Task instructions promoted either enhanced or routine autonomy, and either external or internal focus of attention. These conditions were replicated in a crossover design for two common medical tasks (chest compressions on a manikin and a Fundamentals of Laparoscopic Surgery peg transfer task). Primary outcomes were objective measures of task performance (chest compression deviation from target depth; peg transfer time with penalties for errors). Secondary outcomes included subjective perceptions of confidence, autonomy, and workload. RESULTS: One hundred thirty-three high school students participated in this study. The primary outcomes concerning enhanced vs. routine autonomy demonstrated no statistically significant difference in either task (chest compression depth deviation: difference -0.7 mm [score range 0 to 37.5 mm]; 95% confidence interval (CI95) -3.85, 2.41; p = .65; peg transfer penalized time: rate ratio 1.03; CI95 0.91, 1.31; p = .79). The authors likewise found no statistically significant difference for external vs. internal focus of attention (depth deviation: difference 1.1 mm; CI95 -2.04, 4.17; p = .50; penalized time: rate ratio 0.89; CI95 0.75, 1.13; p = .33). The authors found no statistically significant differences for either comparison in confidence, autonomy and workload (p > .09; differences ranged from -0.83 to 0.79 [scale range 0 to 10]). CONCLUSIONS: First-try performance of chest compressions and peg transfer by novice learners is not significantly affected by enhanced (vs. routine) autonomy or external (vs. internal) focus of attention.

Association of mammographic density measures and breast cancer "intrinsic" molecular subtypes.

PURPOSE: We evaluated the association of percent mammographic density (PMD), absolute dense area (DA), and non-dense area (NDA) with risk of "intrinsic" molecular breast cancer (BC) subtypes. METHODS: We pooled 3492 invasive BC and 10,148 controls across six studies with density measures from prediagnostic, digitized film-screen mammograms. We classified BC tumors into subtypes [63% Luminal A, 21% Luminal B, 5% HER2 expressing, and 11% as triple negative (TN)] using information on estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and tumor grade. We used polytomous logistic regression to calculate odds ratio (OR) and 95% confidence intervals (CI) for density measures (per SD) across the subtypes compared to controls, adjusting for age, body mass index and study, and examined differences by age group. RESULTS: All density measures were similarly associated with BC risk across subtypes. Significant interaction of PMD by age (P = 0.001) was observed for Luminal A tumors, with stronger effect sizes seen for younger women < 45 years (OR = 1.69 per SD PMD) relative to women of older ages (OR = 1.53, ages 65-74, OR = 1.44 ages 75 +). Similar but opposite trends were seen for NDA by age for risk of Luminal A: risk for women: < 45 years (OR = 0.71 per SD NDA) was lower than older women (OR = 0.83 and OR = 0.84 for ages 65-74 and 75 + , respectively) (P < 0.001). Although not significant, similar patterns of associations were seen by age for TN cancers. CONCLUSIONS: Mammographic density measures were associated with risk of all "intrinsic" molecular subtypes. However, findings of significant interactions between age and density measures may have implications for subtype-specific risk models.

Comparison of Dialysis Unit and Home Blood Pressures: An Observational Cohort Study.

RATIONALE & OBJECTIVE: Prior studies of patients receiving maintenance hemodialysis have shown that, on average, blood pressure (BP) measured predialysis is higher than BP measured at home. We hypothesized that a subset of hemodialysis patients has BP that is higher when measured at home than when measured predialysis and this subgroup of patients has a higher prevalence of left ventricular hypertrophy. STUDY DESIGN: Prospective cohort. SETTING & PARTICIPANTS: 97 hypertensive hemodialysis patients enrolled in the Blood Pressure in Dialysis Study (BID), a randomized trial of comparing target predialysis BP ≤140/90 to 155-165/90 mm Hg. EXPOSURE: Differences between predialysis and next-day home systolic BP measured ≥6 times over 1 year. OUTCOME: Left ventricular mass index (LVMI) by cardiac magnetic resonance imaging. ANALYTICAL APPROACH: A hierarchical clustering analysis divided patients into 3 clusters based on the average and variability of differences in systolic predialysis and home BP. Clusters were compared with respect to clinical factors and LVMI. RESULTS: Mean differences between predialysis and home systolic BP were 19.1 (95% CI, 17.0 to 21.1) mm Hg for cluster 1 ("home lower"), 3.7 (95% CI, 1.6 to 5.8) mm Hg for cluster 2 ("home and predialysis similar"), and -9.7 (95% CI, -12.0 to -7.4) mm Hg for cluster 3 ("home higher"). Systolic BP declined during dialysis in clusters 1 and 2 but increased in cluster 3. Interdialytic weight gains did not differ. After adjusting for sex and treatment arm, LVMI was higher in cluster 3 than in clusters 1 and 2: differences in means of 10.6 ± 4.96 (SE) g/m2 (P = 0.04) and 12.0 ± 5.08 g/m2 (P = 0.02), respectively. LIMITATIONS: Limited statistical power. CONCLUSIONS: Nearly one-third of participants had home BPs higher than predialysis BPs. These patients had LVMI higher than those with similar or lower BPs at home, indicating that their BP may have been undertreated.

Speed and quality goals in procedural skills learning: A randomized experiment.

Purpose: Compare time (speed) and product quality goals in a surgical procedural task.Methods: Secondary school students participating in a medical simulation-based training activity participated in a randomized experiment. Each participant completed eight repetitions of a blood vessel ligation. Once, between repetitions four and five, each participant received a randomly-assigned speed goal or quality goal. Outcomes included time and leak-free ligatures.Results: 80 students participated. The speed-goal group performed 18% faster on the final repetition than the quality-goal group, with adjusted fold change (FC) 0.82 (95% confidence interval [CI], 0.71, 0.94; p = 0.01). Conversely, the speed-goal group had fewer high-quality (leak-free) ligatures (odds ratio [OR] 0.36 [95% CI, 0.22, 0.58; p < 0.001]). For the quality-goal group, leaky ligatures took longer post-intervention than leak-free ligatures (FC 1.09 [95% CI, 1.02, 1.17; p = 0.01]), whereas average times for leaky and leak-free ligatures were similar for the speed-goal group (FC 0.97 [95% CI, 0.91, 1.04; p = 0.38]). For a given performance time, the speed-goal group had more leaks post-intervention than the quality-goal group (OR 3.35 [95% CI, 1.58, 7.10; p = 0.002]).Conclusions: Speed and quality goals promote different learning processes and outcomes among novices. Use of both speed and quality goals may facilitate more effective and efficient learning.

Body mass index, mammographic density, and breast cancer risk by estrogen receptor subtype.

BACKGROUND: Obesity and elevated breast density are common risk factors for breast cancer, and their effects may vary by estrogen receptor (ER) subtype. However, their joint effects on ER subtype-specific risk are unknown. Understanding this relationship could enhance risk stratification for screening and prevention. Thus, we assessed the association between breast density and ER subtype according to body mass index (BMI) and menopausal status. METHODS: We conducted a case-control study nested within two mammography screening cohorts, the Mayo Mammography Health Study and the San Francisco Bay Area Breast Cancer SPORE/San Francisco Mammography Registry. Our pooled analysis contained 1538 ER-positive and 285 ER-negative invasive breast cancer cases and 4720 controls matched on age, menopausal status at time of mammogram, and year of mammogram. Percent density was measured on digitized film mammograms using computer-assisted techniques. We used polytomous logistic regression to evaluate the association between percent density and ER subtype by BMI subgroup (normal/underweight, < 25 kg/m2 versus overweight/obese, ≥ 25 kg/m2). We used Wald chi-squared tests to assess for interactions between percent density and BMI. Our analysis was stratified by menopausal status and hormone therapy usage at the time of index mammogram. RESULTS: Percent density was associated with increased risk of overall breast cancer regardless of menopausal status or BMI. However, when analyzing breast cancer across ER subtype, we found a statistically significant (p = 0.008) interaction between percent density and BMI in premenopausal women only. Specifically, elevated percent density was associated with a higher risk of ER-negative than ER-positive cancer in overweight/obese premenopausal women [OR per standard deviation increment 2.17 (95% CI 1.50-3.16) vs 1.33 (95% CI 1.11-1.61) respectively, Pheterogeneity = 0.01]. In postmenopausal women, elevated percent density was associated with similar risk of ER-positive and ER-negative cancers, and no substantive differences were seen after accounting for BMI or hormone therapy usage. CONCLUSIONS: The combination of overweight/obesity and elevated breast density in premenopausal women is associated with a higher risk of ER-negative compared with ER-positive cancer. Eighteen percent of premenopausal women in the USA have elevated BMI and breast density and may benefit from lifestyle modifications involving weight loss and exercise.

Combined effect of volumetric breast density and body mass index on breast cancer risk.

BACKGROUND: Breast density and body mass index (BMI) are used for breast cancer risk stratification. We evaluate whether the positive association between volumetric breast density and breast cancer risk is strengthened with increasing BMI. METHODS: The San Francisco Mammography Registry and Mayo Clinic Rochester identified 781 premenopausal and 1850 postmenopausal women with breast cancer diagnosed between 2007 and 2015 that had a screening digital mammogram at least 6 months prior to diagnosis. Up to three controls (N = 3535) were matched per case on age, race, date, mammography machine, and state. Volumetric percent density (VPD) and dense volume (DV) were measured with Volpara™. Breast cancer risk was assessed with logistic regression stratified by menopause status. Multiplicative interaction tests assessed whether the association of density measures was differential by BMI categories. RESULTS: The increased risk of breast cancer associated with VPD was strengthened with higher BMI for both premenopausal (pinteraction = 0.01) and postmenopausal (pinteraction = 0.0003) women. For BMI < 25, 25-30, and ≥ 30 kg/m2, ORs for breast cancer for a 1 SD increase in VPD were 1.24, 1.65, and 1.97 for premenopausal, and 1.20, 1.55, and 2.25 for postmenopausal women, respectively. ORs for breast cancer for a 1 SD increase in DV were 1.39, 1.33, and 1.51 for premenopausal (pinteraction = 0.58), and 1.31, 1.34, and 1.65 (pinteraction = 0.03) for postmenopausal women for BMI < 25, 25-30 and ≥ 30 kg/m2, respectively. CONCLUSIONS: The effect of volumetric percent density on breast cancer risk is strongest in overweight and obese women. These associations have clinical relevance for informing prevention strategies.

Supporting self-regulation in simulation-based education: a randomized experiment of practice schedules and goals.

Self-regulated learning is optimized when instructional supports are provided. We evaluated three supports for self-regulated simulation-based training: practice schedules, normative comparisons, and learning goals. Participants practiced 5 endoscopy tasks on a physical simulator, then completed 4 repetitions on a virtual reality simulator. Study A compared two practice schedules: sequential (master each task in assigned order) versus unstructured (trainee-defined). Study B compared normative comparisons framed as success (10% of trainees were successful) versus failure (90% of trainees were unsuccessful). Study C compared a time-only goal (go 1 min faster) versus time + quality goal (go 1 min faster with better visualization and scope manipulation). Participants (18 surgery interns, 17 research fellows, 5 medical/college students) were randomly assigned to groups. In Study A, the sequential group had higher task completion (10/19 vs. 1/21; P < .001), longer persistence attempting an ultimately incomplete task (20.0 vs. 15.9 min; P = .03), and higher efficiency (43% vs. 27%; P = .02), but task time was similar between groups (20.0 vs. 22.6 min; P = .23). In Study B, the success orientation group had higher task completion (10/16 vs. 1/24; P < .001) and longer persistence (21.2 vs. 14.6 min; P = .001), but efficiency was similar (33% vs. 35%; P = .84). In Study C, the time-only group had greater efficiency than time + quality (56% vs. 41%; P = .03), but task time did not differ significantly (172 vs. 208 s; P = .07). In this complex motor task, a sequential (vs. unstructured) schedule, success (vs. failure) orientation, and time-only (vs. time + quality) goal improved some (but not all) performance outcomes.

Automated and Clinical Breast Imaging Reporting and Data System Density Measures Predict Risk for Screen-Detected and Interval Cancers: A Case-Control Study.

Background: In 30 states, women who have had screening mammography are informed of their breast density on the basis of Breast Imaging Reporting and Data System (BI-RADS) density categories estimated subjectively by radiologists. Variation in these clinical categories across and within radiologists has led to discussion about whether automated BI-RADS density should be reported instead. Objective: To determine whether breast cancer risk and detection are similar for automated and clinical BI-RADS density measures. Design: Case-control. Setting: San Francisco Mammography Registry and Mayo Clinic. Participants: 1609 women with screen-detected cancer, 351 women with interval invasive cancer, and 4409 matched control participants. Measurements: Automated and clinical BI-RADS density assessed on digital mammography at 2 time points from September 2006 to October 2014, interval and screen-detected breast cancer risk, and mammography sensitivity. Results: Of women whose breast density was categorized by automated BI-RADS more than 6 months to 5 years before diagnosis, those with extremely dense breasts had a 5.65-fold higher interval cancer risk (95% CI, 3.33 to 9.60) and a 1.43-fold higher screen-detected risk (CI, 1.14 to 1.79) than those with scattered fibroglandular densities. Associations of interval and screen-detected cancer with clinical BI-RADS density were similar to those with automated BI-RADS density, regardless of whether density was measured more than 6 months to less than 2 years or 2 to 5 years before diagnosis. Automated and clinical BI-RADS density measures had similar discriminatory accuracy, which was higher for interval than screen-detected cancer (c-statistics: 0.70 vs. 0.62 [P < 0.001] and 0.72 vs. 0.62 [P < 0.001], respectively). Mammography sensitivity was similar for automated and clinical BI-RADS categories: fatty, 93% versus 92%; scattered fibroglandular densities, 90% versus 90%; heterogeneously dense, 82% versus 78%; and extremely dense, 63% versus 64%, respectively. Limitation: Neither automated nor clinical BI-RADS density was assessed on tomosynthesis, an emerging breast screening method. Conclusion: Automated and clinical BI-RADS density similarly predict interval and screen-detected cancer risk, suggesting that either measure may be used to inform women of their breast density. Primary Funding Source: National Cancer Institute.

Combining quantitative and qualitative breast density measures to assess breast cancer risk.

BACKGROUND: Accurately identifying women with dense breasts (Breast Imaging Reporting and Data System [BI-RADS] heterogeneously or extremely dense) who are at high breast cancer risk will facilitate discussions of supplemental imaging and primary prevention. We examined the independent contribution of dense breast volume and BI-RADS breast density to predict invasive breast cancer and whether dense breast volume combined with Breast Cancer Surveillance Consortium (BCSC) risk model factors (age, race/ethnicity, family history of breast cancer, history of breast biopsy, and BI-RADS breast density) improves identifying women with dense breasts at high breast cancer risk. METHODS: We conducted a case-control study of 1720 women with invasive cancer and 3686 control subjects. We calculated ORs and 95% CIs for the effect of BI-RADS breast density and Volpara™ automated dense breast volume on invasive cancer risk, adjusting for other BCSC risk model factors plus body mass index (BMI), and we compared C-statistics between models. We calculated BCSC 5-year breast cancer risk, incorporating the adjusted ORs associated with dense breast volume. RESULTS: Compared with women with BI-RADS scattered fibroglandular densities and second-quartile dense breast volume, women with BI-RADS extremely dense breasts and third- or fourth-quartile dense breast volume (75% of women with extremely dense breasts) had high breast cancer risk (OR 2.87, 95% CI 1.84-4.47, and OR 2.56, 95% CI 1.87-3.52, respectively), whereas women with extremely dense breasts and first- or second-quartile dense breast volume were not at significantly increased breast cancer risk (OR 1.53, 95% CI 0.75-3.09, and OR 1.50, 95% CI 0.82-2.73, respectively). Adding continuous dense breast volume to a model with BCSC risk model factors and BMI increased discriminatory accuracy compared with a model with only BCSC risk model factors (C-statistic 0.639, 95% CI 0.623-0.654, vs. C-statistic 0.614, 95% CI 0.598-0.630, respectively; P < 0.001). Women with dense breasts and fourth-quartile dense breast volume had a BCSC 5-year risk of 2.5%, whereas women with dense breasts and first-quartile dense breast volume had a 5-year risk ≤ 1.8%. CONCLUSIONS: Risk models with automated dense breast volume combined with BI-RADS breast density may better identify women with dense breasts at high breast cancer risk than risk models with either measure alone.

Interaction of mammographic breast density with menopausal status and postmenopausal hormone use in relation to the risk of aggressive breast cancer subtypes.

PURPOSE: We examined the associations of mammographic breast density with breast cancer risk by tumor aggressiveness and by menopausal status and current postmenopausal hormone therapy. METHODS: This study included 2596 invasive breast cancer cases and 4059 controls selected from participants of four nested case-control studies within four established cohorts: the Mayo Mammography Health Study, the Nurses' Health Study, Nurses' Health Study II, and San Francisco Mammography Registry. Percent breast density (PD), absolute dense (DA), and non-dense areas (NDA) were assessed from digitized film-screen mammograms using a computer-assisted threshold technique and standardized across studies. We used polytomous logistic regression to quantify the associations of breast density with breast cancer risk by tumor aggressiveness (defined as presence of at least two of the following tumor characteristics: size ≥2 cm, grade 2/3, ER-negative status, or positive nodes), stratified by menopausal status and current hormone therapy. RESULTS: Overall, the positive association of PD and borderline inverse association of NDA with breast cancer risk was stronger in aggressive vs. non-aggressive tumors (≥51 vs. 11-25% OR 2.50, 95% CI 1.94-3.22 vs. OR 2.03, 95% CI 1.70-2.43, p-heterogeneity = 0.03; NDA 4th vs. 2nd quartile OR 0.54, 95% CI 0.41-0.70 vs. OR 0.71, 95% CI 0.59-0.85, p-heterogeneity = 0.07). However, there were no differences in the association of DA with breast cancer by aggressive status. In the stratified analysis, there was also evidence of a stronger association of PD and NDA with aggressive tumors among postmenopausal women and, in particular, current estrogen+progesterone users (≥51 vs. 11-25% OR 3.24, 95% CI 1.75-6.00 vs. OR 1.93, 95% CI 1.25-2.98, p-heterogeneity = 0.01; NDA 4th vs. 2nd quartile OR 0.43, 95% CI 0.21-0.85 vs. OR 0.56, 95% CI 0.35-0.89, p-heterogeneity = 0.01), even though the interaction was not significant. CONCLUSION: Our findings suggest that associations of mammographic density with breast cancer risk differ by tumor aggressiveness. While there was no strong evidence that these associations differed by menopausal status or hormone therapy, they did appear more prominent among current estrogen+progesterone users.

Mammographic texture and risk of breast cancer by tumor type and estrogen receptor status.

BACKGROUND: Several studies have shown that mammographic texture features are associated with breast cancer risk independent of the contribution of breast density. Thus, texture features may provide novel information for risk stratification. We examined the association of a set of established texture features with breast cancer risk by tumor type and estrogen receptor (ER) status, accounting for breast density. METHODS: This study combines five case-control studies including 1171 breast cancer cases and 1659 controls matched for age, date of mammogram, and study. Mammographic breast density and 46 breast texture features, including first- and second-order features, Fourier transform, and fractal dimension analysis, were evaluated from digitized film-screen mammograms. Logistic regression models evaluated each normalized feature with breast cancer after adjustment for age, body mass index, first-degree family history, percent density, and study. RESULTS: Of the mammographic features analyzed, fractal dimension and second-order statistics features were significantly associated (p < 0.05) with breast cancer. Fractal dimensions for the thresholds equal to 10% and 15% (FD_TH_10 [corrected] and FD_TH_15) [corrected] were associated with an increased risk of breast cancer while thresholds from 60% to 85% (FD_TH_60 to FD_TH_85) [corrected] were associated with a decreased risk. Increasing the FD_TH_75 [corrected] and Energy feature values were associated with a decreased risk of breast cancer while increasing Entropy was associated with an increased [corrected] risk of breast cancer. For example, 1 standard deviation increase of FD_TH_75 [corrected] was associated with a 13% reduced risk of breast cancer (odds ratio = 0.87, 95% confidence interval 0.79-0.95). Overall, the direction of associations between features and ductal carcinoma in situ (DCIS) and invasive cancer, and estrogen receptor positive and negative cancer were similar. CONCLUSION: Mammographic features derived from film-screen mammograms are associated with breast cancer risk independent of percent mammographic density. Some texture features also demonstrated associations for specific tumor types. For future work, we plan to assess risk prediction combining mammographic density and features assessed on digital images.

Comparison of Clinical and Automated Breast Density Measurements: Implications for Risk Prediction and Supplemental Screening.

Purpose To compare the classification of breast density with two automated methods, Volpara (version 1.5.0; Matakina Technology, Wellington, New Zealand) and Quantra (version 2.0; Hologic, Bedford, Mass), with clinical Breast Imaging Reporting and Data System (BI-RADS) density classifications and to examine associations of these measures with breast cancer risk. Materials and Methods In this study, 1911 patients with breast cancer and 4170 control subjects matched for age, race, examination date, and mammography machine were evaluated. Participants underwent mammography at Mayo Clinic or one of four sites within the San Francisco Mammography Registry between 2006 and 2012 and provided informed consent or a waiver for research, in compliance with HIPAA regulations and institutional review board approval. Digital mammograms were retrieved a mean of 2.1 years (range, 6 months to 6 years) before cancer diagnosis, with the corresponding clinical BI-RADS density classifications, and Volpara and Quantra density estimates were generated. Agreement was assessed with weighted κ statistics among control subjects. Breast cancer associations were evaluated with conditional logistic regression, adjusted for age and body mass index. Odds ratios, C statistics, and 95% confidence intervals (CIs) were estimated. Results Agreement between clinical BI-RADS density classifications and Volpara and Quantra BI-RADS estimates was moderate, with κ values of 0.57 (95% CI: 0.55, 0.59) and 0.46 (95% CI: 0.44, 0.47), respectively. Differences of up to 14% in dense tissue classification were found, with Volpara classifying 51% of women as having dense breasts, Quantra classifying 37%, and clinical BI-RADS assessment used to classify 43%. Clinical and automated measures showed similar breast cancer associations; odds ratios for extremely dense breasts versus scattered fibroglandular densities were 1.8 (95% CI: 1.5, 2.2), 1.9 (95% CI: 1.5, 2.5), and 2.3 (95% CI: 1.9, 2.8) for Volpara, Quantra, and BI-RADS classifications, respectively. Clinical BI-RADS assessment showed better discrimination of case status (C = 0.60; 95% CI: 0.58, 0.61) than did Volpara (C = 0.58; 95% CI: 0.56, 0.59) and Quantra (C = 0.56; 95% CI: 0.54, 0.58) BI-RADS classifications. Conclusion Automated and clinical assessments of breast density are similarly associated with breast cancer risk but differ up to 14% in the classification of women with dense breasts. This could have substantial effects on clinical practice patterns. (©) RSNA, 2015 Online supplemental material is available for this article.

A comprehensive evaluation of interaction between genetic variants and use of menopausal hormone therapy on mammographic density.

INTRODUCTION: Mammographic density is an established breast cancer risk factor with a strong genetic component and can be increased in women using menopausal hormone therapy (MHT). Here, we aimed to identify genetic variants that may modify the association between MHT use and mammographic density. METHODS: The study comprised 6,298 postmenopausal women from the Mayo Mammography Health Study and nine studies included in the Breast Cancer Association Consortium. We selected for evaluation 1327 single nucleotide polymorphisms (SNPs) showing the lowest P-values for interaction (P int) in a meta-analysis of genome-wide gene-environment interaction studies with MHT use on risk of breast cancer, 2541 SNPs in candidate genes (AKR1C4, CYP1A1-CYP1A2, CYP1B1, ESR2, PPARG, PRL, SULT1A1-SULT1A2 and TNF) and ten SNPs (AREG-rs10034692, PRDM6-rs186749, ESR1-rs12665607, ZNF365-rs10995190, 8p11.23-rs7816345, LSP1-rs3817198, IGF1-rs703556, 12q24-rs1265507, TMEM184B-rs7289126, and SGSM3-rs17001868) associated with mammographic density in genome-wide studies. We used multiple linear regression models adjusted for potential confounders to evaluate interactions between SNPs and current use of MHT on mammographic density. RESULTS: No significant interactions were identified after adjustment for multiple testing. The strongest SNP-MHT interaction (unadjusted P int <0.0004) was observed with rs9358531 6.5kb 5' of PRL. Furthermore, three SNPs in PLCG2 that had previously been shown to modify the association of MHT use with breast cancer risk were found to modify also the association of MHT use with mammographic density (unadjusted P int <0.002), but solely among cases (unadjusted P int SNP×MHT×case-status <0.02). CONCLUSIONS: The study identified potential interactions on mammographic density between current use of MHT and SNPs near PRL and in PLCG2, which require confirmation. Given the moderate size of the interactions observed, larger studies are needed to identify genetic modifiers of the association of MHT use with mammographic density.