Automated volumetric breast density measures: differential change between breasts in women with and without breast cancer.

BACKGROUND: Given that breast cancer and normal dense fibroglandular tissue have similar radiographic attenuation, we examine whether automated volumetric density measures identify a differential change between breasts in women with cancer and compare to healthy controls. METHODS: Eligible cases (n = 1160) had unilateral invasive breast cancer and bilateral full-field digital mammograms (FFDMs) at two time points: within 2 months and 1-5 years before diagnosis. Controls (n = 2360) were matched to cases on age and date of FFDMs. Dense volume (DV) and volumetric percent density (VPD) for each breast were assessed using Volpara™. Differences in DV and VPD between mammograms (median 3 years apart) were calculated per breast separately for cases and controls and their difference evaluated by using the Wilcoxon signed-rank test. To simulate clinical practice where cancer laterality is unknown, we examined whether the absolute difference between breasts can discriminate cases from controls using area under the ROC curve (AUC) analysis, adjusting for age, BMI, and time. RESULTS: Among cases, the VPD and DV between mammograms of the cancerous breast decreased to a lesser degree (- 0.26% and - 2.10 cm3) than the normal breast (- 0.39% and - 2.74 cm3) for a difference of 0.13% (p value < 0.001) and 0.63 cm3 (p = 0.002), respectively. Among controls, the differences between breasts were nearly identical for VPD (- 0.02 [p = 0.92]) and DV (0.05 [p = 0.77]). The AUC for discriminating cases from controls using absolute difference between breasts was 0.54 (95% CI 0.52, 0.56) for VPD and 0.56 (95% CI, 0.54, 0.58) for DV. CONCLUSION: There is a small relative increase in volumetric density measures over time in the breast with cancer which is not found in the normal breast. However, the magnitude of this difference is small, and this measure alone does not appear to be a good discriminator between women with and without breast cancer.

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.

Gestational diabetes, type II diabetes, and mammographic breast density in a U.S. racially diverse population screened for breast cancer.

PURPOSE: Type II diabetes mellitus (T2DM) has consistently been associated with an increased risk of breast cancer, but the association of gestational diabetes mellitus (GDM) with breast cancer is less clear. T2DM and GDM may influence breast cancer risk through mammographic breast density, a strong risk factor for breast cancer. We examined whether T2DM and GDM are associated with higher mammographic breast density in a largely racial/ethnic minority sample. METHODS: We collected digital mammograms, anthropometric measures, and interview data from 511 racially diverse women recruited during screening mammography appointments between 2012 and 2016 (mean age 51 years; 70% Hispanic). We examined the associations of self-reported GDM, T2DM, and medication use (metformin and insulin) with mammographic breast density, measured as percent and area of dense tissue using Cumulus software. RESULTS: In multivariable linear regression models, history of T2DM and/or GDM and length of time since diagnosis were not associated with percent density or dense breast area, either before or after adjustment for current BMI. Use of metformin in diabetic women was associated with lower percent density (ß = - 5.73, 95% CI - 10.27, - 1.19), only before adjusting for BMI. These associations were not modified by menopausal status. CONCLUSIONS: Our results do not support associations between T2DM and/or GDM and higher amount of mammographically dense breast tissue, suggesting that the mechanism linking diabetes with breast cancer risk may not include mammographic breast density in midlife.

The metabolic syndrome and mammographic breast density in a racially diverse and predominantly immigrant sample of women.

PURPOSE: The metabolic syndrome [MetS, clustering of elevated blood pressure, triglycerides and glucose, reduced high-density lipoprotein cholesterol (HDL-C), abdominal obesity] has been associated with increased breast cancer risk, but less is known about its association with mammographic breast density, a strong risk factor for breast cancer. METHODS: We collected data on risk factors, body size, and blood pressure via in-person interviews and examinations and measured glucose, triglycerides, and HDL-C from dried blood spots from women recruited through a mammography screening clinic (n = 373; 68 % Hispanic, 17 % African-American, 63 % foreign born). We performed linear regression models to examine the associations of each MetS component and the MetS cluster (≥3 components) with percent density and dense breast area, measured using a computer-assisted technique and Cumulus software. RESULTS: About 45 % of women had the MetS, with the prevalence of the individual components ranging from 68 % for abdominal obesity to 33 % for elevated triglycerides. The prevalence of the MetS increased with higher body mass index (BMI) and postmenopausal status, but did not vary substantially by ethnicity, immigrant generational status, parity, age at menarche, or alcohol consumption. Low HDL-C (<50 mg/dL), but not the MetS cluster or the other MetS components, was associated with larger dense breast area after adjusting for age, BMI, fasting time, and educational attainment (ß = 8.77, 95 % CI 2.39, 15.14). The MetS and its individual components were not associated with BMI-adjusted percent density. CONCLUSIONS: HDL-C alone may have an influence on dense breast tissue that is independent of BMI, and may be in the same direction as its association with breast cancer risk.

A complex systems model of breast cancer etiology: The Paradigm II Model.

BACKGROUND: Complex systems models of breast cancer have previously focused on prediction of prognosis and clinical events for individual women. There is a need for understanding breast cancer at the population level for public health decision-making, for identifying gaps in epidemiologic knowledge and for the education of the public as to the complexity of this most common of cancers. METHODS AND FINDINGS: We developed an agent-based model of breast cancer for the women of the state of California using data from the U.S. Census, the California Health Interview Survey, the California Cancer Registry, the National Health and Nutrition Examination Survey and the literature. The model was implemented in the Julia programming language and R computing environment. The Paradigm II model development followed a transdisciplinary process with expertise from multiple relevant disciplinary experts from genetics to epidemiology and sociology with the goal of exploring both upstream determinants at the population level and pathophysiologic etiologic factors at the biologic level. The resulting model reproduces in a reasonable manner the overall age-specific incidence curve for the years 2008-2012 and incidence and relative risks due to specific risk factors such as BRCA1, polygenic risk, alcohol consumption, hormone therapy, breastfeeding, oral contraceptive use and scenarios for environmental toxin exposures. CONCLUSIONS: The Paradigm II model illustrates the role of multiple etiologic factors in breast cancer from domains of biology, behavior and the environment. The value of the model is in providing a virtual laboratory to evaluate a wide range of potential interventions into the social, environmental and behavioral determinants of breast cancer at the population level.

Patients' access to rare neuromuscular disease therapies varies across US private insurers.

BACKGROUND: The extent to which different US private insurers require their enrollees to meet the same coverage criteria before gaining access to treatment is unclear. Our objective was to scrutinize the patient access criteria imposed by US private insurers for a set of rare neuromuscular disease (NMD) disease-modifying therapies (DMTs). METHODS: We examined coverage policies issued by 17 large US private insurers for the following NMD treatments: nusinersen and onasemnogene abeparvovec for spinal muscular atrophy, edaravone for amyotrophic lateral sclerosis, and eteplirsen for Duchenne muscular dystrophy. We reviewed the plans' coverage policies and identified the patient access criteria, including clinical prerequisites, step therapy protocols, and prescriber requirements. We compared the plans' patient access criteria with the therapies' US Food and Drug Administration (FDA)-labeled indications. RESULTS: The included insurers issued 65 coverage policies for the included therapies. Plans imposed coverage restrictions beyond the FDA-approved indications in 60 coverage policies; plans did not cover eteplirsen in five policies. No therapy was covered the same way by all insurers. Plans applied clinical criteria beyond the FDA label indication in 56 policies and step therapy protocols in three policies. Plans required that a neurologist prescribe the therapy in 37 policies, 22 of which required the neurologist to have expertise in the particular disease. Plans often required patients to suffer from symptoms of particular severity; e.g. for eteplirsen, plans differed in their 6-min walk test requirements; for edaravone, some plans required that patients had normal respiratory function, while others required only that patients did not require ventilation; for nusinersen and onasemnogene abeparvovec, plans differed in the number of SMN2 gene copies they required patients to have (SMN2 copy number is correlated with disease severity). CONCLUSIONS: The evaluated large US private insurers tended to impose coverage restrictions beyond the FDA label indication for the included set of rare NMD DMTs. Plans rarely applied the same patient access criteria in their coverage policies for the same products. Inconsistent coverage criteria mean that patients with different insurers have variable access to the same therapies across insurers.

Work Productivity Outcomes Associated with Ocrelizumab Compared with Other Disease-Modifying Therapies for Multiple Sclerosis.

OBJECTIVE: This study evaluated work and activity impairment in patients with multiple sclerosis (MS) treated with ocrelizumab (OCR) versus other disease-modifying therapies (DMTs). METHODS: Data were obtained from the Adelphi Real World Disease Specific Programme for Multiple Sclerosis. Patients with relapsing-remitting or secondary progressive MS who completed surveys in 2018 and 2019 and received ≥ 6 months of an eligible therapy, including OCR, injectable therapy, and oral therapy, were included. Outcomes were assessed using the patient-reported Work Productivity and Activity Impairment questionnaire. Doubly robust estimation, which combined propensity score weighting and regression modeling, was used to compare treatments, controlling for baseline clinical and demographic characteristics. RESULTS: This study included 630 patients (OCR, n = 90; injectable DMT, n = 224; oral DMT, n = 316) with a mean (standard deviation) age of 42 (11) years. A greater proportion of OCR-treated patients had an Expanded Disability Status Scale score of ≥ 3 at treatment initiation compared with those receiving oral and injectable DMTs (51 vs. 15% and 15%, respectively), and a smaller proportion of OCR-treated patients received treatment for ≥ 1 year (43 vs. 90% and 92%, respectively). OCR-treated patients had higher odds of employment [odds ratio (95% confidence interval) 3.4 (1.5-7.7) vs. oral DMT, 5.6 (2.6-12.0) vs. injectable DMT], lower overall work productivity loss [difference (95% confidence interval) - 10.0% (- 6.1 to - 15.0%) vs. oral DMT, - 13.0% (- 8.5 to - 17.0%) vs. injectable DMT] and lower activity impairment [difference (95% confidence interval) - 11% (- 7.1 to - 16.0%) vs. oral DMT, - 9.7% (- 5.0 to - 14.0%) vs. injectable DMT]. CONCLUSION: This real-world evidence suggests that patients with MS treated with OCR experience lower work and activity impairment than patients treated with other DMTs.

Multiple sclerosis (MS) is the most common progressive neurological disease in young adults. It typically starts between the ages of 20 and 40 years­arguably some of the most productive years of an individual's life­and it has a large impact on many aspects of everyday life for the rest of a person's life. The reduction in the ability to do routine activities, including working, results in a large economic burden. Disease-modifying treatments (DMTs) available for MS, particularly high-efficacy DMTs, have been shown to improve work productivity. This study looked at work and activity impairment using the Work Productivity and Activity Impairment Questionnaire in patients with MS who were treated with ocrelizumab (OCR) or other DMTs for ≥ 6 months. A total of 630 patients with relapsing­remitting MS (RRMS) or secondary progressive MS (SPMS) from the Adelphi Real World Disease Specific Programme for Multiple Sclerosis were included in the study, including 90, 316 and 224 patients who completed ≥ 6 months of treatment with OCR, oral or injectable therapy. Compared with patients receiving oral or injectable DMTs, those receiving OCR had higher odds of employment [odds ratio (OR) vs. oral DMT 3.4; OR vs. injectable DMT 5.6], lower overall work productivity impairment (difference vs. oral DMT − 10%; difference vs. injectable DMT − 13%) and lower activity impairment (difference vs. oral DMT − 11%; difference vs. injectable DMT − 9.7%). These findings in patients with RRMS or SPMS being treated in the real world suggest that OCR may reduce the impact of MS disease on work productivity more than other DMTs.

Persistence and adherence to ocrelizumab compared with other disease-modifying therapies for multiple sclerosis in U.S. commercial claims data.

BACKGROUND: Ocrelizumab (OCR) is the only disease-modifying therapy (DMT) for both relapsing and primary progressive forms of multiple sclerosis (MS). OCR is given by intravenous (IV) infusion twice a year, which may improve adherence to the dosing schedule relative to other MS DMTs that require more frequent administration. Real-world evidence on the persistence and adherence of patients with MS to OCR compared with other DMTs is limited. OBJECTIVE: To examine the persistence and adherence to OCR compared with other DMTs for MS in the United States. METHODS: This analysis was conducted in the PharMetrics Plus commercial claims database and included patients with MS who initiated a new DMT between April 2017 and September 2018. Patients were required to have health plan enrollment for ≥ 1 year before and after DMT initiation (a subgroup analysis was performed for those with ≥ 18 months' continuous enrollment after DMT initiation). Persistence was defined as not switching to another DMT and having no gap in coverage of the initiated DMT for ≥ 60 days during the postinitiation period. The proportion of days covered (PDC) was calculated as the total days covered by the DMT during the postinitiation period divided by the length of the time period (12 or 18 months); PDC ≥ 0.8 was considered adherent. Multivariable Poisson regression models compared discontinuation (nonpersistence) and nonadherence between OCR users and users of other DMTs grouped by administration route. RESULTS: A total of 4,587 patients (OCR, 1,319; injectable, 1,051; oral, 1,876; other IV, 341) were included. The OCR group had the lowest proportion of patients discontinuing at 12 months (8% vs. 28%, 32%, and 43% for other IV, oral, and injectable, respectively) and the highest mean PDC (93% vs. 76%, 74%, and 69%, respectively). Compared with patients initiating OCR, adjusted relative risks (RR) of 12-month discontinuation were 3.3 (95% CI = 2.3-4.6), 3.8 (95% CI = 3.0-4.9), and 5.5 (95% CI = 4.1-7.5) for patients initiating other IV, oral, and injectable DMTs, respectively. Similarly, patients initiating other IV, oral, and injectable DMTs had RRs of 4.9 (95% CI = 3.6-6.8), 5.1 (95% CI = 3.9-6.6), and 6.8 (95% CI = 5.0-9.3) for 12-month nonadherence compared with OCR. A subgroup of 2,913 patients with 18 months of continuous enrollment had similar trends, with 17% in the OCR group discontinuing compared with 40%, 41%, and 55% in the other IV, oral, and injectable groups, respectively. Trends over 18 months were consistent with the 12-month analysis in adjusted models. CONCLUSIONS: Patients initiating OCR had superior persistence and adherence at 12 and 18 months of follow-up compared with patients initiating other MS DMTs. Long-term persistence and adherence should be monitored as OCR experience accrues in a real-world setting. DISCLOSURES: This study was funded by Genentech (South San Francisco, CA), a member of the Roche Group. Engmann, Sheinson, Bawa, and Ng are employees of Genentech and shareholders of F. Hoffman-La Roche (Basel, Switzerland).

A Complex Systems Model of Breast Cancer Etiology: The Paradigm II Conceptual Model.

BACKGROUND: The etiology of breast cancer is a complex system of interacting factors from multiple domains. New knowledge about breast cancer etiology continues to be produced by the research community, and the communication of this knowledge to other researchers, practitioners, decision makers, and the public is a challenge. METHODS: We updated the previously published Paradigm model (PMID: 25017248) to create a framework that describes breast cancer etiology in four overlapping domains of biologic, behavioral, environmental, and social determinants. This new Paradigm II conceptual model was part of a larger modeling effort that included input from multiple experts in fields from genetics to sociology, taking a team and transdisciplinary approach to the common problem of describing breast cancer etiology for the population of California women in 2010. Recent literature was reviewed with an emphasis on systematic reviews when available and larger epidemiologic studies when they were not. Environmental chemicals with strong animal data on etiology were also included. RESULTS: The resulting model illustrates factors with their strength of association and the quality of the available data. The published evidence supporting each relationship is made available herein, and also in an online dynamic model that allows for manipulation of individual factors leading to breast cancer (https://cbcrp.org/causes/). CONCLUSIONS: The Paradigm II model illustrates known etiologic factors in breast cancer, as well as gaps in knowledge and areas where better quality data are needed. IMPACT: The Paradigm II model can be a stimulus for further research and for better understanding of breast cancer etiology.

In utero DDT exposure and breast density in early menopause by maternal history of breast cancer.

We examined the relationship between intrauterine dichlorodiphenyltrichloroethane (DDT) exposure (o,p'-DDT, p,p'-DDT, and p,p'-DDE) and mammographic breast density (MBD) in midlife, one of the strongest risk factors for breast cancer. We focused our analyses on o,p'-DDT exposure given our previous report of a positive association between intrauterine o,p'-DDT exposure and daughter's breast cancer (BC) risk. Here we estimated associations of intrauterine serum DDTs with MBD in 224 daughters of women in the Child Health and Development Studies pregnancy cohort whose mothers did not develop BC (MBCa-) and 156 daughters whose mothers did develop BC (MBCa+). In MBCa+ daughters, highest relative to lowest quartile of o,p'-DDT exposure was associated with a 17-unit higher dense area (95% CI = 2.6-31.2; Ptrend = 0.01). We did not observe an association between o,p'-DDT and density measures in MBCa- daughters. MBD, an intermediate marker of BC risk, may be affected by intrauterine DDT exposures; MBCa status may modify the association.

An exploratory analysis of the efficacy of ocrelizumab in patients with multiple sclerosis with increased disability.

BACKGROUND: Ocrelizumab, an anti-CD20 humanized monoclonal antibody, reduced disease progression in pivotal trials of patients with relapsing (OPERA I, OPERA II) and primary progressive (ORATORIO) multiple sclerosis (MS). These effects may be particularly important among patients with increased disability. OBJECTIVE: In this post hoc exploratory analysis, we evaluated the efficacy of ocrelizumab on disability progression among a subgroup of patients with MS who had increased baseline disability levels (Expanded Disability Status Scale scores ≥4.0) in the pivotal trials. METHODS: During the double-blind period, patients received ocrelizumab 600 mg intravenously every 24 weeks for 96 weeks in the OPERA trials (versus interferon ß-1a 44 µg subcutaneously three times per week) and for 120 weeks in ORATORIO (versus placebo). Kaplan-Meier and Cox survival analyses were used to assess disability outcome measures. RESULTS: Baseline demographic, disease, and treatment characteristics were generally comparable across treatment groups in patients with increased disability from the OPERA and ORATORIO trials. Ocrelizumab treatment numerically, and in some instances significantly, reduced confirmed disability progression versus the comparator in these patients. CONCLUSIONS: In patients with increased baseline disability, ocrelizumab reduced the risk of confirmed disability progression versus interferon ß-1a in patients with relapsing-onset MS and versus placebo in patients with progression-onset MS.

Longitudinal Changes in Volumetric Breast Density in Healthy Women across the Menopausal Transition.

BACKGROUND: Mammographic breast density declines during menopause. We assessed changes in volumetric breast density across the menopausal transition and factors that influence these changes. METHODS: Women without a history of breast cancer, who had full field digital mammograms during both pre- and postmenopausal periods, at least 2 years apart, were sampled from four facilities within the San Francisco Mammography Registry from 2007 to 2013. Dense breast volume (DV) was assessed using Volpara on mammograms across the time period. Annualized change in DV from pre- to postmenopause was estimated using linear mixed models adjusted for covariates and per-woman random effects. Multiplicative interactions were evaluated between premenopausal risk factors and time to determine whether these covariates modified the annualized changes. RESULTS: Among the 2,586 eligible women, 1,802 had one premenopausal and one postmenopausal mammogram, 628 had an additional perimenopausal mammogram, and 156 had two perimenopausal mammograms. Women experienced an annualized decrease in DV [-2.2 cm3 (95% confidence interval, -2.7 to -1.7)] over the menopausal transition. Declines were greater among women with a premenopausal DV above the median (54 cm3) versus below (DV, -3.5 cm3 vs. -1.0 cm3; P < 0.0001). Other breast cancer risk factors, including race, body mass index, family history, alcohol, and postmenopausal hormone therapy, had no effect on change in DV over the menopausal transition. CONCLUSIONS: High premenopausal DV was a strong predictor of greater reductions in DV across the menopausal transition. IMPACT: We found that few factors other than premenopausal density influence changes in DV across the menopausal transition, limiting targeted prevention efforts.

Population-Attributable Risk Proportion of Clinical Risk Factors for Breast Cancer.

IMPORTANCE: Many established breast cancer risk factors are used in clinical risk prediction models, although the proportion of breast cancers explained by these factors is unknown. OBJECTIVE: To determine the population-attributable risk proportion (PARP) for breast cancer associated with clinical breast cancer risk factors among premenopausal and postmenopausal women. DESIGN, SETTING, AND PARTICIPANTS: Case-control study with 1:10 matching on age, year of risk factor assessment, and Breast Cancer Surveillance Consortium (BCSC) registry. Risk factor data were collected prospectively from January 1, 1996, through October 31, 2012, from BCSC community-based breast imaging facilities. A total of 18 437 women with invasive breast cancer or ductal carcinoma in situ were enrolled as cases and matched to 184 309 women without breast cancer, with a total of 58 146 premenopausal and 144 600 postmenopausal women enrolled in the study. EXPOSURES: Breast Imaging Reporting and Data System (BI-RADS) breast density (heterogeneously or extremely dense vs scattered fibroglandular densities), first-degree family history of breast cancer, body mass index (>25 vs 18.5-25), history of benign breast biopsy, and nulliparity or age at first birth (≥30 years vs <30 years). MAIN OUTCOMES AND MEASURES: Population-attributable risk proportion of breast cancer. RESULTS: Of the 18 437 women with breast cancer, the mean (SD) age was 46.3 (3.7) years among premenopausal women and 61.7 (7.2) years among the postmenopausal women. Overall, 4747 (89.8%) premenopausal and 12 502 (95.1%) postmenopausal women with breast cancer had at least 1 breast cancer risk factor. The combined PARP of all risk factors was 52.7% (95% CI, 49.1%-56.3%) among premenopausal women and 54.7% (95% CI, 46.5%-54.7%) among postmenopausal women. Breast density was the most prevalent risk factor for both premenopausal and postmenopausal women and had the largest effect on the PARP; 39.3% (95% CI, 36.6%-42.0%) of premenopausal and 26.2% (95% CI, 24.4%-28.0%) of postmenopausal breast cancers could potentially be averted if all women with heterogeneously or extremely dense breasts shifted to scattered fibroglandular breast density. Among postmenopausal women, 22.8% (95% CI, 18.3%-27.3%) of breast cancers could potentially be averted if all overweight and obese women attained a body mass index of less than 25. CONCLUSIONS AND RELEVANCE: Most women with breast cancer have at least 1 breast cancer risk factor routinely documented at the time of mammography, and more than half of premenopausal and postmenopausal breast cancers are explained by these factors. These easily assessed risk factors should be incorporated into risk prediction models to stratify breast cancer risk and promote risk-based screening and targeted prevention efforts.

Genetic Ancestry Is not Associated with Breast Cancer Recurrence or Survival in U.S. Latina Women Enrolled in the Kaiser Permanente Pathways Study.

Background: The U.S. Hispanic/Latino population is heterogeneous both socioculturally and by the proportion of European, Indigenous American, and African ancestry of the regions from which individuals originate. A previous study reported that genetic ancestry was associated with breast cancer survival among Latinas, independent of sociodemographic and tumor characteristics, suggesting that a genetic factor associated with ancestry may affect breast cancer survival.Methods: We evaluated the association of genetic ancestry with breast cancer outcomes among 506 Latina women with invasive breast cancer in the Pathways Study, a cohort study within Kaiser Permanente, an integrated health care delivery system. Proportional hazards models were used to assess the effect of ancestry on breast cancer recurrence (53 events), breast cancer-specific mortality (31 events) and all-cause mortality (54 events), with a mean follow-up time of 6 years.Results: Indigenous American ancestry was not associated with breast cancer recurrence [HR = 1.00 per 10% increase; 95% confidence interval (CI), 0.86-1.16], breast cancer mortality (HR = 0.95; 95% CI, 0.77-1.17), or all-cause mortality (HR = 0.93; 95% CI, 0.80-1.08). Adjustment for sociodemographic variables, tumor characteristics, and treatment did not alter the associations.Conclusions: Our results suggest that previously reported differences in breast cancer survival by genetic ancestry may be overcome by improving health care access and/or quality.Impact: Improving health care access and quality may reduce breast cancer disparities among U.S. Latinas. Cancer Epidemiol Biomarkers Prev; 26(9); 1466-9. ©2017 AACR.

Population Health Science: A Core Element of Health Science Education in Sub-Saharan Africa.

Sub-Saharan Africa suffers an inordinate burden of disease and does not have the numbers of suitably trained health care workers to address this challenge. New concepts in health sciences education are needed to offer alternatives to current training approaches.A perspective of integrated training in population health for undergraduate medical and nursing education is advanced, rather than continuing to take separate approaches for clinical and public health education. Population health science educates students in the social and environmental origins of disease, thus complementing disease-specific training and providing opportunities for learners to take the perspective of the community as a critical part of their education.Many of the recent initiatives in health science education in sub-Saharan Africa are reviewed, and two case studies of innovative change in undergraduate medical education are presented that begin to incorporate such population health thinking. The focus is on East Africa, one of the most rapidly growing economies in sub-Saharan Africa where opportunities for change in health science education are opening. The authors conclude that a focus on population health is a timely and effective way for enhancing training of health care professionals to reduce the burden of disease in sub-Saharan Africa.

Longitudinal Changes in Volumetric Breast Density with Tamoxifen and Aromatase Inhibitors.

Background: Reductions in breast density with tamoxifen and aromatase inhibitors may be an intermediate marker of treatment response. We compare changes in volumetric breast density among breast cancer cases using tamoxifen or aromatase inhibitors (AI) to untreated women without breast cancer.Methods: Breast cancer cases with a digital mammogram prior to diagnosis and after initiation of tamoxifen (n = 366) or AI (n = 403) and a sample of controls (n = 2170) were identified from the Mayo Clinic Mammography Practice and San Francisco Mammography Registry. Volumetric percent density (VPD) and dense breast volume (DV) were measured using Volpara (Matakina Technology) and Quantra (Hologic) software. Linear regression estimated the effect of treatment on annualized changes in density.Results: Premenopausal women using tamoxifen experienced annualized declines in VPD of 1.17% to 1.70% compared with 0.30% to 0.56% for controls and declines in DV of 7.43 to 15.13 cm3 compared with 0.28 to 0.63 cm3 in controls, for Volpara and Quantra, respectively. The greatest reductions were observed among women with ≥10% baseline density. Postmenopausal AI users had greater declines in VPD than controls (Volpara P = 0.02; Quantra P = 0.03), and reductions were greatest among women with ≥10% baseline density. Declines in VPD among postmenopausal women using tamoxifen were only statistically greater than controls when measured with Quantra.Conclusions: Automated software can detect volumetric breast density changes among women on tamoxifen and AI.Impact: If declines in volumetric density predict breast cancer outcomes, these measures may be used as interim prognostic indicators. Cancer Epidemiol Biomarkers Prev; 26(6); 930-7. ©2017 AACR.

Multiple metabolic risk factors and mammographic breast density.

PURPOSE: We examined whether obesity and a history of diabetes, hypertension, and elevated cholesterol, individually and in combination, are associated with breast density, a strong risk factor for breast cancer. METHODS: We measured percent density and dense area using a computer-assisted method (n = 191; age range = 40-61 years). We used linear regression models to examine the associations of each metabolic condition and the number of metabolic conditions (zero, one, two, and three or four conditions) with breast density. RESULTS: Among individual metabolic conditions, only high blood cholesterol was inversely associated with percent density (ß = -5.4, 95% confidence interval [CI]: -8.5, -2.2) and dense area (ß = -6.7, 95% CI = -11.1, -2.4). Having multiple metabolic conditions was also associated with lower breast density, with two conditions and three or four conditions versus zero conditions associated with 6.4% (95% CI: -11.2, -1.6) and 7.4% (95% CI: -12.9, -1.9) reduction in percent density and with 6.5 cm(2) (95% CI: -13.1, -0.1) and 9.5 cm(2) (95% CI: -17.1, -1.9) decrease in dense area. CONCLUSIONS: A history of high blood cholesterol and multiple metabolic conditions were associated with lower relative and absolute measures of breast density. The positive association between metabolic abnormalities and breast cancer risk may be driven by pathways unrelated to mammographic breast density.