Publications by authors named "Diana S M Buist"

234 Publications

Factors to Consider in Developing Breast Cancer Risk Models to Implement into Clinical Care.

Authors:
Diana S M Buist

Curr Epidemiol Rep 2020 Jun 29;7(2):113-116. Epub 2020 Apr 29.

Kaiser Permanente Washington Health Research Institute, Seattle WA.

Purpose Of The Review: This article outlines considerations for individuals interested in developing and implementing breast cancer risk models and has relevance for individuals developing risk-models with the goal of implementing them into health systems.

Recent Findings: There has been increased focus on developing risk models for clinical use-often with less attention model implementation. Epidemiologists developing risk-models must think through model outcomes including stakeholder needs, time horizons, terminology and reference groups and clarity on what actionable steps are for health systems, providers and patients following its implementation.

Summary: Model performance needs to be evaluated relative to complexity of the model to be implemented-not just from the risk-prediction perspective, but also from the burden on patients, providers and systems for the amount and frequency of required data collection and with clear actionable steps to be taken with the information collected.
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http://dx.doi.org/10.1007/s40471-020-00230-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7863773PMC
June 2020

Association of the Intensity of Diagnostic Evaluation With Outcomes in Incidentally Detected Lung Nodules.

JAMA Intern Med 2021 Jan 19. Epub 2021 Jan 19.

Kaiser Permanente Bernard J. Tyson School of Medicine, Pasadena, California.

Importance: Whether guideline-concordant lung nodule evaluations lead to better outcomes remains unknown.

Objective: To examine the association between the intensity of lung nodule diagnostic evaluations and outcomes, safety, and health expenditures.

Design, Setting, And Participants: This comparative effectiveness research study analyzed health plan enrollees at Kaiser Permanente Washington in Seattle, Washington, and Marshfield Clinic in Marshfield, Wisconsin, with an incidental lung nodule detected between January 1, 2005, and December 31, 2015. Included patients were 35 years or older, had no high suspicion of infection, had no history of malignant neoplasm, and had no evidence of advanced lung cancer on nodule detection. Data analysis was conducted from January 7 to August 19, 2020.

Exposures: With the 2005 Fleischner Society guidelines (selected for their applicability to the time frame under investigation) as the comparator, 2 other intensities of lung nodule evaluation were defined. Guideline-concordant evaluation followed the guidelines. Less intensive evaluation was the absence of recommended testing, longer-than-recommended surveillance intervals, or less invasive testing than recommended. More intensive evaluation consisted of testing when the guidelines recommended no further testing, shorter-than-recommended surveillance intervals, or more invasive testing than recommended.

Main Outcomes And Measures: The main outcome was the proportion of patients with lung cancer who had stage III or IV disease, radiation exposure, procedure-related adverse events, and health expenditures 2 years after nodule detection.

Results: Among the 5057 individuals included in this comparative effectiveness research study, 1925 (38%) received guideline-concordant, 1863 (37%) less intensive, and 1269 (25%) more intensive diagnostic evaluations. The entire cohort comprised 2786 female patients (55%), and the mean (SD) age was 67 (13) years. Adjusted analyses showed that compared with guideline-concordant evaluations, less intensive evaluations were associated with fewer procedure-related adverse events (risk difference [RD], -5.9%; 95% CI, -7.2% to -4.6%), lower mean radiation exposure (-9.5 milliSieverts [mSv]; 95% CI, -10.3 mSv to -8.7 mSv), and lower mean health expenditures (-$10 916; 95% CI, -$16 112 to -$5719); no difference in stage III or IV disease was found among patients diagnosed with lung cancer (RD, 4.6%; 95% CI, -22% to +31%). More intensive evaluations were associated with more procedure-related adverse events (RD, +8.1%; 95% CI, +5.6% to +11%), higher mean radiation exposure (+6.8 mSv; 95% CI, +5.8 mSv to +7.8 mSv), and higher mean health expenditures ($20 132; 95% CI, +$14 398 to +$25 868); no difference in stage III or IV disease was observed (RD, -0.5%; 95% CI, -28% to +27%).

Conclusions And Relevance: This study found inconclusive evidence of an association between less intensive diagnostic evaluations and more advanced stage at lung cancer diagnosis compared with guideline-concordant care; higher intensities of diagnostic evaluations were associated with greater procedural complications, radiation exposure, and expenditures. These findings underscore the need for more evidence on better ways to evaluate lung nodules and to avoid unnecessarily intensive diagnostic evaluations of lung nodules.
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http://dx.doi.org/10.1001/jamainternmed.2020.8250DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7816118PMC
January 2021

Out of reach? Correlates of cervical cancer underscreening in women with varying levels of healthcare interactions in a United States integrated delivery system.

Prev Med 2020 Dec 31;145:106410. Epub 2020 Dec 31.

Department of Epidemiology, University of Washington, Seattle, WA, USA; Kaiser Permanente Washington Health Research Institute, Seattle, WA, USA. Electronic address:

One in five U.S. women with health insurance are underscreened for cervical cancer. We sought to identify whether underscreening correlates differed among women with different levels of health care interaction. Among women age 30-64 years who were members of an integrated U.S. health system, we used 2014-2015 electronic health record data to identify underscreened cases (≥3.4 years since last Papanicolaou (Pap) test, n=3352) and screening-adherent controls (<3.4 years since last Pap test, n=45,359) and extracted data on potential underscreening correlates (demographics, health history, and healthcare utilization). We calculated the odds of underscreening in the total population and by subgroups defined by healthcare visits and online health portal usage in the prior 12 months. Underscreening was associated with older age (50-64 vs. 30-39; odds ratio (OR)=1.6; 95%CI=1.4-1.8), current tobacco use (vs. never use; OR=2.1; 95%CI=1.8-2.2), higher BMI (≥35 kg/m vs <25 kg/m, OR=2.0; 95%CI=1.8-2.3), screening non-adherence for colorectal cancer (OR=5.1; 95%CI=4.6-5.7) and breast cancer (OR=8.1, 95%CI=7.2-9.0), and having no recent visit with their primary care provider (PCP) nor recent health portal use (vs. recent PCP visit and portal use; OR=8.4, 95%CI=7.6-9.4). Underscreening correlates were similar between the total study population and within all healthcare interaction groups. Interaction with the healthcare system is associated with lower odds of underscreening, but sociodemographic and health status correlates are similar regardless of primary care visits or online portal use. These data support the need for additional interventions to reach insured women who remain underscreened for cervical cancer.
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http://dx.doi.org/10.1016/j.ypmed.2020.106410DOI Listing
December 2020

Advanced Breast Cancer Definitions by Staging System Examined in the Breast Cancer Surveillance Consortium.

J Natl Cancer Inst 2020 Nov 10. Epub 2020 Nov 10.

Department of Public Health Sciences, University of California, Davis, CA.

Background: Advanced breast cancer is an outcome used to evaluate screening effectiveness. The advanced cancer definition resulting in the best discrimination of breast cancer death has not been studied in a breast imaging population.

Methods: 52,496 women aged 40-79 years participating in the Breast Cancer Surveillance Consortium diagnosed with invasive cancer were staged using the eighth edition of American Joint Committee on Cancer (AJCC) anatomic and prognostic pathologic systems and Tomosynthesis Mammographic Imaging Screening Trial (TMIST) tumor categories. We calculated the area under the receiver operating characteristic curve (AUC) for predicting 5-year breast cancer death and the sensitivity and specificity for predicting 5-year breast cancer death for three advanced cancer classifications; anatomic stage IIB or higher, prognostic pathologic stage IIA or higher, and TMIST advanced cancer.

Results: The AUCs for predicting 5-year breast cancer death for AJCC anatomic stage, AJCC prognostic pathologic stage, and TMIST tumor categories were 0.826 (95% confidence interval [CI]=0.817, 0.835), 0.856 (95%CI = 0.846, 0.866), and 0.789 (95%CI = 0.780, 0.797), respectively. AJCC prognostic pathologic stage had statistically significantly better discrimination than AJCC anatomic stage (difference = 0.030, bootstrap 95%CI = 0.024, 0.037) and TMIST tumor categories (difference = 0.067, bootstrap 95%CI = 0.059, 0.075). The sensitivity and specificity for predicting 5-year breast cancer death for AJCC anatomic stage IIB or higher, AJCC prognostic pathologic stage IIA or higher, and TMIST advanced cancer were (72.6%, 76.7%, 96.1%) and (78.9%, 81.6%, 41.1%), respectively.

Conclusion: Defining advanced cancer as AJCC prognostic pathologic stage IIA or higher most accurately predicts breast cancer death. Use of this definition by investigators will facilitate comparing breast cancer screening effectiveness studies.
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http://dx.doi.org/10.1093/jnci/djaa176DOI Listing
November 2020

Association of Circulating Progesterone With Breast Cancer Risk Among Postmenopausal Women.

JAMA Netw Open 2020 04 1;3(4):e203645. Epub 2020 Apr 1.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.

Importance: The role of endogenous progesterone in the development of breast cancer remains largely unexplored to date, primarily owing to assay sensitivity limitations and low progesterone concentrations in postmenopausal women. Recently identified progesterone metabolites may provide insights as experimental data suggest that 5α-dihydroprogesterone (5αP) concentrations reflect cancer-promoting properties and 3α-dihydroprogesterone (3αHP) concentrations reflect cancer-inhibiting properties.

Objective: To evaluate the association between circulating progesterone and progesterone metabolite levels and breast cancer risk.

Design, Setting, And Participants: Using a sensitive liquid chromatography-tandem mass spectrometry assay, prediagnostic serum levels of progesterone and progesterone metabolites were quantified in a case-cohort study nested within the Breast and Bone Follow-up to the Fracture Intervention Trial (n = 15 595). Participation was limited to women not receiving exogenous hormone therapy at the time of blood sampling (1992-1993). Incident breast cancer cases (n = 405) were diagnosed during 12 follow-up years and a subcohort of 495 postmenopausal women were randomly selected within 10-year age and clinical center strata. Progesterone assays were completed in July 2017; subsequent data analyses were conducted between July 15, 2017, and December 20, 2018.

Exposures: Circulating concentrations of pregnenolone, progesterone, and their major metabolites.

Main Outcomes And Measures: Development of breast cancer, with hazard ratios (HRs) and 95% CIs was estimated using Cox proportional hazards regression adjusted for key confounders, including estradiol. Evaluation of hormone ratios and effect modification were planned a priori.

Results: The present study included 405 incident breast cancer cases and a subcohort of 495 postmenopausal women; the mean (SD) age at the time of the blood draw was 67.2 (6.2) years. Progesterone concentrations were a mean (SD) of 4.6 (1.7) ng/dL. Women with higher circulating progesterone levels were at an increased risk for breast cancer per SD increase in progesterone levels (HR, 1.16; 95% CI, 1.00-1.35; P = .048). The association with progesterone was linear in a 5-knot spline and stronger for invasive breast cancers (n = 267) (HR, 1.24; 95% CI, 1.07-1.43; P = .004). Among women in the lowest quintile (Q1) of circulating estradiol (<6.30 pg/mL) elevated progesterone concentrations were associated with reduced breast cancer risk per SD increase in progesterone levels (HR, 0.38; 95% CI, 0.15-0.95; P = .04) and increased risk among women in higher quintiles of estradiol (Q2-Q5; ≥6.30 pg/mL) (HR, 1.18; 95% CI, 1.04-1.35; P = .01; P = .04 for interaction).

Conclusions And Relevance: In this case-cohort study of postmenopausal women, elevated circulating progesterone levels were associated with a 16% increase in the risk of breast cancer. Additional research should be undertaken to assess how postmenopausal breast cancer risk is associated with both endogenous progesterone and progesterone metabolites and their interactions with estradiol.
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http://dx.doi.org/10.1001/jamanetworkopen.2020.3645DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7182797PMC
April 2020

Authors' response: Cost-effectiveness evidence for HPV self-sampling could be improved by giving greater attention to vulnerable populations.

Prev Med 2020 10 4;139:106081. Epub 2020 Apr 4.

Department of Epidemiology, University of Washington, Box 359933, 325 9th Ave, Seattle, WA 98104, USA; Kaiser Permanente Washington Health Research Institute,1730 Minor Ave, Suite 1600, Seattle, WA 98101, USA. Electronic address:

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http://dx.doi.org/10.1016/j.ypmed.2020.106081DOI Listing
October 2020

Future Research Suggestions for Multigene Testing in Unselected Populations-Reply.

JAMA Oncol 2020 05;6(5):785-786

Genomic Medicine, Manchester Academic Health Science Centre, Manchester Universities Foundation Trust, St Mary's Hospital, The University of Manchester, Manchester, United Kingdom.

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http://dx.doi.org/10.1001/jamaoncol.2020.0131DOI Listing
May 2020

Evaluation of Combined Artificial Intelligence and Radiologist Assessment to Interpret Screening Mammograms.

JAMA Netw Open 2020 03 2;3(3):e200265. Epub 2020 Mar 2.

Korea University, Seoul, Korea.

Importance: Mammography screening currently relies on subjective human interpretation. Artificial intelligence (AI) advances could be used to increase mammography screening accuracy by reducing missed cancers and false positives.

Objective: To evaluate whether AI can overcome human mammography interpretation limitations with a rigorous, unbiased evaluation of machine learning algorithms.

Design, Setting, And Participants: In this diagnostic accuracy study conducted between September 2016 and November 2017, an international, crowdsourced challenge was hosted to foster AI algorithm development focused on interpreting screening mammography. More than 1100 participants comprising 126 teams from 44 countries participated. Analysis began November 18, 2016.

Main Outcomes And Measurements: Algorithms used images alone (challenge 1) or combined images, previous examinations (if available), and clinical and demographic risk factor data (challenge 2) and output a score that translated to cancer yes/no within 12 months. Algorithm accuracy for breast cancer detection was evaluated using area under the curve and algorithm specificity compared with radiologists' specificity with radiologists' sensitivity set at 85.9% (United States) and 83.9% (Sweden). An ensemble method aggregating top-performing AI algorithms and radiologists' recall assessment was developed and evaluated.

Results: Overall, 144 231 screening mammograms from 85 580 US women (952 cancer positive ≤12 months from screening) were used for algorithm training and validation. A second independent validation cohort included 166 578 examinations from 68 008 Swedish women (780 cancer positive). The top-performing algorithm achieved an area under the curve of 0.858 (United States) and 0.903 (Sweden) and 66.2% (United States) and 81.2% (Sweden) specificity at the radiologists' sensitivity, lower than community-practice radiologists' specificity of 90.5% (United States) and 98.5% (Sweden). Combining top-performing algorithms and US radiologist assessments resulted in a higher area under the curve of 0.942 and achieved a significantly improved specificity (92.0%) at the same sensitivity.

Conclusions And Relevance: While no single AI algorithm outperformed radiologists, an ensemble of AI algorithms combined with radiologist assessment in a single-reader screening environment improved overall accuracy. This study underscores the potential of using machine learning methods for enhancing mammography screening interpretation.
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http://dx.doi.org/10.1001/jamanetworkopen.2020.0265DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7052735PMC
March 2020

Facility Variability in Examination Indication Among Women With Prior Breast Cancer: Implications and the Need for Standardization.

J Am Coll Radiol 2020 Jun 28;17(6):755-764. Epub 2020 Jan 28.

Department of Radiology, University of Washington School of Medicine, Seattle, Washington.

Objective: We sought to identify and characterize examinations in women with a personal history of breast cancer likely performed for asymptomatic surveillance.

Methods: We included surveillance mammograms (1997-2017) in asymptomatic women with a personal history of breast cancer diagnosed at age ≥18 years (1996-2016) from 103 Breast Cancer Surveillance Consortium facilities. We examined facility-level variability in examination indication. We modeled the relative risk (RR) and 95% confidence intervals (CIs) at the examination level of a (1) nonscreening indication and (2) surveillance interval ≤9 months using Poisson regression with fixed effects for facility, stage, diagnosis age, surgery, examination year, and time since diagnosis.

Results: Among 244,855 surveillance mammograms, 69.5% were coded with a screening indication, 12.7% short-interval follow-up, and 15.3% as evaluation of a breast problem. Within a facility, the proportion of examinations with a screening indication ranged from 6% to 100% (median 86%, interquartile range 79%-92%). Facilities varied the most for examinations in the first 5 years after diagnosis, with 39.4% of surveillance mammograms having a nonscreening indication. Within a facility, breast conserving surgery compared with mastectomy (RR = 1.64; 95% CI = 1.60-1.68) and less time since diagnosis (1 year versus 5 years; RR = 1.69; 95% CI = 1.66-1.72; 3 years versus 5 years = 1.20; 95% CI = 1.18-1.23) were strongly associated with a nonscreening indication with similar results for ≤9-month surveillance interval. Screening indication and >9-month surveillance intervals were more common in more recent years.

Conclusion: Variability in surveillance indications across facilities in the United States supports including indications beyond screening in studies evaluating surveillance mammography effectiveness and demonstrates the need for standardization.
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http://dx.doi.org/10.1016/j.jacr.2019.12.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7275918PMC
June 2020

Cost-effectiveness studies of HPV self-sampling: A systematic review.

Prev Med 2020 03 3;132:105953. Epub 2020 Jan 3.

Department of Epidemiology, University of Washington, Box 359933, 325 9th Ave, Seattle, WA 98104, USA; Kaiser Permanente Washington Health Research Institute,1730 Minor Ave, Suite 1600, Seattle, WA 98101, USA. Electronic address:

HPV self-sampling (HPV-SS) can increase cervical cancer screening participation by addressing barriers in high- and low- and middle-income settings. Successful implementation of HPV-SS programs will depend on understanding potential costs and health effects. Our objectives were to summarize the methods and results of published HPV-SS cost and cost-effectiveness studies, present implications of these results for HPV-SS program implementation, and identify knowledge gaps. We followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. One reviewer searched online databases for articles published through June 12, 2019, identified eligible studies, and extracted data; a second reviewer checked extracted data for accuracy. Eligible studies used an economic model to compare HPV-SS outreach strategies to standard-of-care tests. Of 16 eligible studies, 14 reported HPV-SS could be a cost-effective strategy. Studies differed in model type, HPV-SS delivery methods, triage strategies for positive results, and target populations. Most (9/16) modeled HPV-SS in European screening programs, 6/16 targeted women who were underscreened for cervical cancer, and 5/16 modeled HPV-SS in low- and middle-income countries. The most commonly identified driver of HPV-SS cost-effectiveness was the level of increase in cervical cancer screening attendance. Lower HPV-SS material and testing costs, higher sensitivity to detect cervical precancer, and longer duration of underscreening among HPV-SS users were also associated with increased cost-effectiveness. Future HPV-SS models in high-income settings should explore the effect of widespread vaccination and new triage strategies such as partial HPV genotyping. Knowledge gaps remain about the cost-effectiveness of HPV-SS in low- and middle-income settings.
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http://dx.doi.org/10.1016/j.ypmed.2019.105953DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7219564PMC
March 2020

Knowledge and Perception of Breast Density, Screening Mammography, and Supplemental Screening: in Search of "Informed".

J Gen Intern Med 2020 06 2;35(6):1654-1660. Epub 2019 Dec 2.

Kaiser Permanente Washington Health Research Institute, Seattle, WA, USA.

Background: As of 2019, 37 US states have breast density notification laws. No qualitative study to date has examined women's perspectives about breast density in general or by states with and without notification laws.

Objective: Explore women's knowledge and perceptions of breast density and experiences of breast cancer screening across three states with and without notification laws.

Design: Qualitative research design using four focus groups conducted in 2017.

Participants: Forty-seven women who had a recent normal mammogram and dense breasts in registry data obtained through the Breast Cancer Surveillance Consortium.

Approach: Focus groups were 90 min, audio recorded, and transcribed for analysis. Data were analyzed using mixed deductive and inductive coding.

Key Results: Women reported variable knowledge levels of personal breast density and breast density in general, even among women living in states with a notification law. A number of women were aware of the difficulty of detecting cancer with dense breasts, but only one knew that density increased breast cancer risk. Across all states, very few women reported receiving information about breast density during healthcare visits beyond being encouraged to get supplemental imaging or to pay for new mammography technology (i.e., breast tomosynthesis). Women offered more imaging or different technology held strong convictions that these were "better," even though knowledge of differences, effectiveness, or harms across technologies seemed limited. Women from all states expressed a strong desire for more information about breast density.

Conclusions: More research needs to be done to understand how the medical community can best assist women in making informed decisions related to breast density, mammography, and supplemental screening. Options to explore include improved breast density notifications and education materials about breast density, continued development of personalized risk information tools, strategies for providers to discuss evidence and options based on risk stratification, and shared decision-making.
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http://dx.doi.org/10.1007/s11606-019-05560-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7280373PMC
June 2020

Comorbidity Index Score Increases Due to Coding Artifacts.

Epidemiology 2020 03;31(2):e13-e15

Kaiser Permanente Washington, Health Research Institute, Seattle, WA,

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http://dx.doi.org/10.1097/EDE.0000000000001142DOI Listing
March 2020

Effect of Mailed Human Papillomavirus Test Kits vs Usual Care Reminders on Cervical Cancer Screening Uptake, Precancer Detection, and Treatment: A Randomized Clinical Trial.

JAMA Netw Open 2019 11 1;2(11):e1914729. Epub 2019 Nov 1.

Kaiser Permanente Washington Health Research Institute, Seattle.

Importance: In the United States, more than 50% of cervical cancers are diagnosed in underscreened women. Cervical cancer screening guidelines now include primary human papillomavirus (HPV) testing as a recommended strategy. Home-based HPV self-sampling is a viable option for increasing screening compliance and effectiveness; however, US data are needed to inform health care system implementation.

Objective: To evaluate effectiveness of mailed HPV self-sampling kits vs usual care reminders for in-clinic screening to increase detection and treatment of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) and uptake of cervical cancer screening.

Design, Setting, And Participants: Randomized clinical trial conducted in Kaiser Permanente Washington, a US integrated health care delivery system. Women aged 30 to 64 years with health plan enrollment for 3 years and 5 months or more, a primary care clinician, no Papanicolaou test within 3 years and 5 months, and no hysterectomy were identified through electronic medical records and enrolled from February 25, 2014, to August 29, 2016, with follow-up through February 26, 2018.

Interventions: The control group received usual care (annual patient reminders and ad hoc outreach from primary care clinics). The intervention group received usual care plus a mailed HPV self-sampling kit.

Main Outcomes And Measures: Two primary outcomes were (1) CIN2+ detection within 6 months of screening and (2) treatment within 6 months of CIN2+ detection. Screening uptake within 6 months of randomization was a secondary outcome.

Results: A total of 19 851 women (mean [SD] age, 50.1 [9.5] years) were included, with 9960 randomized to the intervention group and 9891 randomized to the control group. All women randomized were included in analysis. In the intervention group, 12 participants with CIN2+ were detected compared with 8 in the control group (relative risk, 1.49; 95% CI, 0.61-3.64) and 12 cases were treated vs 7 in the control group (relative risk, 1.70; 95% CI, 0.67-4.32). Screening uptake was higher in the intervention group (2618 participants [26.3%] vs 1719 participants [17.4%]; relative risk, 1.51; 95% CI, 1.43-1.60).

Conclusions And Relevance: Mailing HPV kits to underscreened women increased screening uptake compared with usual care alone, with no significant differences in precancer detection or treatment. Results support the feasibility of mailing HPV kits to women who are overdue for screening as an outreach strategy to increase screening uptake in US health care systems. Efforts to increase kit uptake and follow-up of positive results are warranted to maximize detection and treatment of CIN2+.

Trial Registration: ClinicalTrials.gov identifier: NCT02005510.
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http://dx.doi.org/10.1001/jamanetworkopen.2019.14729DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6865279PMC
November 2019

Screening Mammography Outcomes: Risk of Breast Cancer and Mortality by Comorbidity Score and Age.

J Natl Cancer Inst 2020 06;112(6):599-606

University of California, San Francisco, San Francisco.

Background: Potential benefits of screening mammography among women ages 75 years and older remain unclear.

Methods: We evaluated 10-year cumulative incidence of breast cancer and death from breast cancer and other causes by Charlson Comorbidity Index (CCI) and age in the Medicare-linked Breast Cancer Surveillance Consortium (1999-2010) cohort of 222 088 women with no less than 1 screening mammogram between ages 66 and 94 years.

Results: During median follow-up of 107 months, 7583 were diagnosed with invasive breast cancer and 1742 with ductal carcinoma in situ; 471 died from breast cancer and 42 229 from other causes. The 10-year cumulative incidence of invasive breast cancer did not change with increasing CCI but decreased slightly with age: ages 66-74 years (CCI0 = 4.0% [95% CI = 3.9% to 4.2%] vs CCI  ≥ 2 = 3.9% [95% CI = 3.5% to 4.3%]); ages 75-84 years (CCI0 = 3.7% [95% CI = 3.5% to 3.9%] vs CCI  ≥ 2 = 3.4% [95% CI = 2.9% to 3.9%]); and ages 85-94 years (CCI0 = 2.7% [95% CI = 2.3% to 3.1%] vs CCI  ≥ 2 = 2.1% [95% CI = 1.3% to 3.0%]). The 10-year cumulative incidence of other-cause death increased with increasing CCI and age: ages 66-74 years (CCI0 = 10.4% [95% CI = 10.3 to 10.7%] vs CCI ≥ 2 = 43.4% [95% CI = 42.2% to 44.4%]), ages 75-84 years (CCI0 = 29.8% [95% CI = 29.3% to 30.2%] vs CCI ≥ 2 = 61.7% [95% CI = 60.2% to 63.3%]), and ages 85 to 94 years (CCI0 = 60.3% [95% CI = 59.1% to 61.5%] vs CCI  ≥ 2 = 84.8% [95% CI = 82.5% to 86.9%]). The 10-year cumulative incidence of breast cancer death was small and did not vary by age: ages 66-74 years = 0.2% (95% CI = 0.2% to 0.3%), ages 75-84 years = 0.29% (95% CI = 0.25% to 0.34%), and ages 85 to 94 years = 0.3% (95% CI = 0.2% to 0.4%).

Conclusions: Cumulative incidence of other-cause death was many times higher than breast cancer incidence and death, depending on comorbidity and age. Hence, older women with increased comorbidity may experience diminished benefit from continued screening.
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http://dx.doi.org/10.1093/jnci/djz172DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7301094PMC
June 2020

A Cost-effectiveness Analysis of Multigene Testing for All Patients With Breast Cancer.

JAMA Oncol 2019 Oct 3. Epub 2019 Oct 3.

Centre for Experimental Cancer Medicine, Barts Cancer Institute, Queen Mary University of London, London, United Kingdom.

Importance: Moving to multigene testing for all women with breast cancer (BC) could identify many more mutation carriers who can benefit from precision prevention. However, the cost-effectiveness of this approach remains unaddressed.

Objective: To estimate incremental lifetime effects, costs, and cost-effectiveness of multigene testing of all patients with BC compared with the current practice of genetic testing (BRCA) based on family history (FH) or clinical criteria.

Design, Setting, And Participants: This cost-effectiveness microsimulation modeling study compared lifetime costs and effects of high-risk BRCA1/BRCA2/PALB2 (multigene) testing of all unselected patients with BC (strategy A) with BRCA1/BRCA2 testing based on FH or clinical criteria (strategy B) in United Kingdom (UK) and US populations. Data were obtained from 11 836 patients in population-based BC cohorts (regardless of FH) recruited to 4 large research studies. Data were collected and analyzed from January 1, 2018, through June 8, 2019. The time horizon is lifetime. Payer and societal perspectives are presented. Probabilistic and 1-way sensitivity analyses evaluate model uncertainty.

Interventions: In strategy A, all women with BC underwent BRCA1/BRCA2/PALB2 testing. In strategy B, only women with BC fulfilling FH or clinical criteria underwent BRCA testing. Affected BRCA/PALB2 carriers could undertake contralateral preventive mastectomy; BRCA carriers could choose risk-reducing salpingo-oophorectomy (RRSO). Relatives of mutation carriers underwent cascade testing. Unaffected relative carriers could undergo magnetic resonance imaging or mammography screening, chemoprevention, or risk-reducing mastectomy for BC risk and RRSO for ovarian cancer (OC) risk.

Main Outcomes And Measures: Incremental cost-effectiveness ratio (ICER) was calculated as incremental cost per quality-adjusted life-year (QALY) gained and compared with standard £30 000/QALY and $100 000/QALY UK and US thresholds, respectively. Incidence of OC, BC, excess deaths due to heart disease, and the overall population effects were estimated.

Results: BRCA1/BRCA2/PALB2 multigene testing for all patients detected with BC annually would cost £10 464/QALY (payer perspective) or £7216/QALY (societal perspective) in the United Kingdom or $65 661/QALY (payer perspective) or $61 618/QALY (societal perspective) in the United States compared with current BRCA testing based on clinical criteria or FH. This is well below UK and US cost-effectiveness thresholds. In probabilistic sensitivity analysis, unselected multigene testing remained cost-effective for 98% to 99% of UK and 64% to 68% of US health system simulations. One year's unselected multigene testing could prevent 2101 cases of BC and OC and 633 deaths in the United Kingdom and 9733 cases of BC and OC and 2406 deaths in the United States. Correspondingly, 8 excess deaths due to heart disease occurred in the United Kingdom and 35 in the United States annually.

Conclusions And Relevance: This study found unselected, high-risk multigene testing for all patients with BC to be extremely cost-effective compared with testing based on FH or clinical criteria for UK and US health systems. These findings support changing current policy to expand genetic testing to all women with BC.
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http://dx.doi.org/10.1001/jamaoncol.2019.3323DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6777250PMC
October 2019

Pathways to breast cancer screening artificial intelligence algorithm validation.

Breast 2020 Aug 9;52:146-149. Epub 2019 Sep 9.

Kaiser Permanente Washington Health Research Institute, Seattle, WA, USA.

As more artificial intelligence (AI)-enhanced mammography screening tools enter the clinical market, greater focus will be placed on external validation in diverse patient populations. In this viewpoint, we outline lessons learned from prior efforts in this field, the need to validate algorithms on newer screening technologies and diverse patient populations, and conclude by discussing the need for a framework for continuous monitoring and recalibration of these AI tools. Sufficient validation and continuous monitoring of emerging AI tools for breast cancer screening will require greater stakeholder engagement and the creation of shared policies and guidelines.
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http://dx.doi.org/10.1016/j.breast.2019.09.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7061055PMC
August 2020

Patterns of Breast Imaging Use Among Women with a Personal History of Breast Cancer.

J Gen Intern Med 2019 10 13;34(10):2098-2106. Epub 2019 Aug 13.

Kaiser Permanente Washington Health Research Institute, Seattle, WA, USA.

Background: National patterns of breast imaging in women with a personal history of breast cancer (PHBC) are unknown making evaluation of annual surveillance recommendations a challenge.

Objective: To describe variation in use of mammography and breast magnetic resonance imaging (MRI) examinations beginning 6 months after diagnosis among women with PHBC in US community practice. We report on the breast imaging indication, imaging intervals, and time since breast cancer diagnosis by examination type.

Design: Longitudinal study using cross-sectional data.

Setting: Breast Cancer Surveillance Consortium breast imaging facilities.

Participants: 19,955 women diagnosed between 2005 and 2012 with AJCC stage 0-III incident breast cancer who had 69,386 mammograms and 3,553 breast MRI examinations from January 2005 to September 2013; median follow-up of 37.6 months (interquartile range, 22.1-60.7).

Main Measures: Breast imaging indication, imaging intervals, and time since breast cancer diagnosis by examination type.

Key Results: Among women with a PHBC who received breast imaging, 89.4% underwent mammography alone, 0.8% MRI alone, and 10.3% had both mammography and MRI. About half of mammograms and MRIs were indicated for surveillance vs. diagnostic, with an increase in the proportion of surveillance exams as time from diagnosis increased (mammograms, 45.7% at 1 year to 72.2% after 5 years; MRIs, 54.8% at 1 year to 78.6% after 5 years). In the first post-diagnosis period, 32.8% of women had > 2 breast imaging examinations and of these, 65.8% were less than 6 months apart. During the first 5-year post-diagnosis, the frequency of examinations per year decreased and the interval between examinations shifted towards annual examinations.

Conclusion: In women with a PHBC who received post-diagnosis imaging, a third underwent multiple breast imaging examinations per year during the first 2-year post-diagnosis despite recommendations for annual exams. As time since diagnosis increases, imaging indication shifts from diagnostic to surveillance.
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http://dx.doi.org/10.1007/s11606-019-05181-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6816668PMC
October 2019

Strategies to Identify Women at High Risk of Advanced Breast Cancer During Routine Screening for Discussion of Supplemental Imaging.

JAMA Intern Med 2019 Jul 1. Epub 2019 Jul 1.

Kaiser Permanente Washington Health Research Institute, Kaiser Permanente Washington, Seattle.

Importance: Federal legislation proposes requiring that screening mammography reports to practitioners and women incorporate breast density information and that women with dense breasts discuss supplemental imaging with their practitioner given their increased risk of interval breast cancer. Instead of discussing supplemental imaging with all women with dense breasts, it may be more efficient to identify women at high risk of advanced breast cancer who may benefit most from supplemental imaging.

Objective: To identify women at high risk of advanced breast cancer to target woman-practitioner discussions about the need for supplemental imaging.

Design, Setting, And Participants: This prospective cohort study assessed 638 856 women aged 40 to 74 years who had 1 693 163 screening digital mammograms taken at Breast Cancer Surveillance Consortium (BCSC) imaging facilities from January 3, 2005, to December 31, 2014. Data analysis was performed from October 10, 2018, to March 20, 2019.

Exposures: Breast Imaging Reporting and Data System (BI-RADS) breast density and BCSC 5-year breast cancer risk.

Main Outcomes And Measures: Advanced breast cancer (stage IIB or higher) within 12 months of screening mammography; high advanced cancer rates (≥0.61 cases per 1000 mammograms) defined as the top 25th percentile of advanced cancer rates, and discussions per potential advanced cancer prevented.

Results: A total of 638 856 women (mean [SD] age, 56.5 [8.9] years) were included in the study. Women with dense breasts (heterogeneously or extremely dense) accounted for 47.0% of screened women and 60.0% of advanced cancers. Low advanced cancer rates (<0.61 per 1000 mammograms) occurred in 34.5% of screened women with dense breasts. High advanced breast cancer rates occurred in women with heterogeneously dense breasts and a 5-year risk of 2.5% or higher (6.0% of screened women) and those with extremely dense breasts and a 5-year risk of 1.0% or higher (6.5% of screened women). Density-risk subgroups at high advanced cancer risk comprised 12.5% of screened women and 27.1% of advanced cancers. Density-risk subgroups had the fewest supplemental imaging discussions per potential advanced cancer prevented compared with a strategy based on dense breasts (1097 vs 1866 discussions). Women with heterogeneously dense breasts and a 5-year risk less than 1.67% (21.7% of screened women) had high rates of false-positive short-interval follow-up recommendation without undergoing supplemental imaging.

Conclusions And Relevance: The findings suggest that breast density notification should be combined with breast cancer risk so women at highest risk for advanced cancer are targeted for supplemental imaging discussions and women at low risk are not. BI-RADS breast density combined with BCSC 5-year risk may offer a more efficient strategy for supplemental imaging discussions than targeting all women with dense breasts.
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http://dx.doi.org/10.1001/jamainternmed.2019.1758DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6604099PMC
July 2019

Re: Cancer Outcomes in DCIS Patients Without Locoregional Treatment.

J Natl Cancer Inst 2020 02;112(2):214-215

Washington Health Research Institute, Kaiser Permanente Washington, Seattle, WA (DSMB).

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http://dx.doi.org/10.1093/jnci/djz118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7019086PMC
February 2020

Surveillance Breast MRI and Mammography: Comparison in Women with a Personal History of Breast Cancer.

Radiology 2019 08 4;292(2):311-318. Epub 2019 Jun 4.

From the Kaiser Permanente Washington Health Research Institute, 1730 Minor Ave, Suite 1600, Seattle, WA 98101 (K.J.W., L.I., D.S.M.B., S.D.B., M.B., D.J., D.L.M.); Departments of Medicine and Epidemiology and Biostatistics, General Internal Medicine Section, Department of Veterans Affairs, University of California, San Francisco, San Francisco, Calif (K.K.); Department of Radiology, University of North Carolina, Chapel Hill, NC (L.M.H.); Department of Medicine, Brigham and Women's Hospital, Boston, Mass (L.N.); Department of Biomedical Data Science, Norris Cotton Cancer Center, Dartmouth Medical School, Hanover, NH (T.O.); Departments of Surgery and Radiology, University of Vermont, Burlington, Vt (B.L.S.); Department of Radiology, University of Washington, Seattle Cancer Care Alliance Seattle, Wash (J.M.L.); Department of Radiology, Massachusetts General Hospital, Boston, Mass (C.D.L.); Department of Public Health Sciences, University of California, Davis, Davis, Calif (D.L.M.).

Background There is lack of consensus regarding the use of breast MRI for routine surveillance for second breast cancer events in women with a personal history of breast cancer. Purpose To compare performance of surveillance mammography with breast MRI. Materials and Methods This observational cohort study used prospectively collected data and included 13 266 women age 18 years and older (mean age, 60 years ± 13) with stage 0-III breast cancer who underwent 33 938 mammographic examinations and 2506 breast MRI examinations from 2005 to 2012 in the Breast Cancer Surveillance Consortium. Women were categorized into two groups: mammography alone ( = 11 745) or breast MRI ( = 1521). Performance measures were calculated by using end-of-day assessment and occurrence of second breast cancer events within 1 year of imaging. Logistic regression was used to compare performance for breast MRI versus mammography alone, adjusting for women, examination, and primary breast cancer characteristics. Analysis was conducted on a per-examination basis. Results Breast MRI was associated with younger age at diagnosis, chemotherapy, and higher education and income. Raw performance measures for breast MRI versus mammography were as follows, respectively: cancer detection rates, 10.8 (95% confidence interval [CI]: 6.7, 14.8) versus 8.2 (95% CI: 7.3, 9.2) per 1000 examinations; sensitivity, 61.4% (27 of 44; 95% CI: 46.5%, 76.2%) versus 70.3% (279 of 397; 95% CI: 65.8%, 74.8%); and biopsy rate, 10.1% (253 of 2506; 95% CI: 8.9%, 11.3%) versus 4.0% (1343 of 33 938; 95% CI: 3.7%, 4.2%). In multivariable models, breast MRI was associated with higher biopsy rate (odds ratio [OR], 2.2; 95% CI: 1.9, 2.7; < .001) and cancer detection rate (OR, 1.7; 95% CI: 1.1, 2.7; = .03) than mammography alone. However, there were no differences in sensitivity (OR, 1.1; 95% CI: 0.4, 2.9; = .84) or interval cancer rate (OR, 1.1; 95% CI: 0.6, 2.2; = .70). Conclusion Comparison of the performance of surveillance breast MRI with mammography must account for patient characteristics. Whereas breast MRI leads to higher biopsy and cancer detection rates, there were no significant differences in sensitivity or interval cancers compared with mammography. © RSNA, 2019 See also the editorial by Newell in this issue.
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http://dx.doi.org/10.1148/radiol.2019182475DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6694722PMC
August 2019

Collaborating on Data, Science, and Infrastructure: The 20-Year Journey of the Cancer Research Network.

EGEMS (Wash DC) 2019 Mar 29;7(1). Epub 2019 Mar 29.

Health Care Systems Research Network, Seattle, WA, US.

The Cancer Research Network (CRN) is a consortium of 12 research groups, each affiliated with a nonprofit integrated health care delivery system, that was first funded in 1998. The overall goal of the CRN is to support and facilitate collaborative cancer research within its component delivery systems. This paper describes the CRN's 20-year experience and evolution. The network combined its members' scientific capabilities and data resources to create an infrastructure that has ultimately supported over 275 projects. Insights about the strengths and limitations of electronic health data for research, approaches to optimizing multidisciplinary collaboration, and the role of a health services research infrastructure to complement traditional clinical trials and large observational datasets are described, along with recommendations for other research consortia.
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http://dx.doi.org/10.5334/egems.273DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6450242PMC
March 2019

Digital Breast Tomosynthesis: Radiologist Learning Curve.

Radiology 2019 04 26;291(1):34-42. Epub 2019 Feb 26.

From the Division of Biostatistics, Department of Public Health Sciences, University of California, Davis School of Medicine, One Shields Ave, Med Sci 1C, Room 144, Davis, CA 95616 (D.L.M.); Kaiser Permanente Washington Health Research Institute, Kaiser Permanente Washington, Seattle, Wash (D.L.M., L.A., D.S.M.B.); Department of Radiology, University of Washington School of Medicine; Department of Health Services, University of Washington School of Public Health; Hutchinson Institute for Cancer Outcomes Research, Seattle, Wash (C.I.L.); Department of Radiology (S.D.H.) and Department of Surgery, Office of Health Promotion Research (B.L.S.), Larner College of Medicine at the University of Vermont and University of Vermont Cancer Center, Burlington, Vt; Department of Radiology, University of North Carolina, Chapel Hill, NC (L.M.H.); The Dartmouth Institute for Health Policy and Clinical Practice, Geisel School of Medicine at Dartmouth and Norris Cotton Cancer Center, Lebanon, NH (A.N.A.T.); and Departments of Medicine andEpidemiology and Biostatistics and the General Internal Medicine Section, Department of Veterans Affairs, University of California, San Francisco, Calif (K.K.).

Background There is growing evidence that digital breast tomosynthesis (DBT) results in lower recall rates and higher cancer detection rates when compared with digital mammography. However, whether DBT interpretative performance changes with experience (learning curve effect) is unknown. Purpose To evaluate screening DBT performance by cumulative DBT volume within 2 years after adoption relative to digital mammography (DM) performance 1 year before DBT adoption. Materials and Methods This prospective study included 106 126 DBT and 221 248 DM examinations in 271 362 women (mean age, 57.5 years) from 2010 to 2017 that were interpreted by 104 radiologists from 53 facilities in the Breast Cancer Surveillance Consortium. Conditional logistic regression was used to estimate within-radiologist effects of increasing cumulative DBT volume on recall and cancer detection rates relative to DM and was adjusted for examination-level characteristics. Changes were also evaluated by subspecialty and breast density. Results Before DBT adoption, DM recall rate was 10.4% (95% confidence interval [CI]: 9.5%, 11.4%) and cancer detection rate was 4.0 per 1000 screenings (95% CI: 3.6 per 1000 screenings, 4.5 per 1000 screenings); after DBT adoption, DBT recall rate was lower (9.4%; 95% CI: 8.2%, 10.6%; P = .02) and cancer detection rate was similar (4.6 per 1000 screenings; 95% CI: 4.0 per 1000 screenings, 5.2 per 1000 screenings; P = .12). Relative to DM, DBT recall rate decreased for a cumulative DBT volume of fewer than 400 studies (odds ratio [OR] = 0.83; 95% CI: 0.78, 0.89) and remained lower as volume increased (400-799 studies, OR = 0.8 [95% CI: 0.75, 0.85]; 800-1199 studies, OR = 0.81 [95% CI: 0.76, 0.87]; 1200-1599 studies, OR = 0.78 [95% CI: 0.73, 0.84]; 1600-2000 studies, OR = 0.81 [95% CI: 0.75, 0.88]; P < .001). Improvements were sustained for breast imaging subspecialists (OR range, 0.67-0.85; P < .02) and readers who were not breast imaging specialists (OR range, 0.80-0.85; P < .001). Recall rates decreased more in women with nondense breasts (OR range, 0.68-0.76; P < .001) than in those with dense breasts (OR range, 0.86-0.90; P ≤ .05; P interaction < .001). Cancer detection rates for DM and DBT were similar, regardless of DBT volume (P ≥ .10). Conclusion Early performance improvements after digital breast tomosynthesis (DBT) adoption were sustained regardless of DBT volume, radiologist subspecialty, or breast density. © RSNA, 2019 See also the editorial by Hooley in this issue.
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http://dx.doi.org/10.1148/radiol.2019182305DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6438358PMC
April 2019

Trends in BRCA Test Utilization in an Integrated Health System, 2005-2015.

J Natl Cancer Inst 2019 08;111(8):795-802

See the Notes section for the authors' affiliations.

Background: Genetic testing to determine BRCA status has been available for over two decades, but there are few population-based studies of test diffusion. We report 10-year trends in BRCAtesting in an integrated health-care system with long-standing access to genetic services.

Methods: A cohort of women aged 18 years and older was created to ascertain BRCA testing (n = 295 087). Annual testing rates between 2005 and 2015 were calculated in all women with and without incident (ie, newly diagnosed) breast and ovarian cancers and in clinically eligible subgroups by family cancer history, personal cancer history, and age at diagnosis. Secular trends were assessed using Poisson regression. Women tested early (2005-2008), midway (2009-2012), and late (2013-2015) in the study period were compared in cross-sectional analyses.

Results: Between 2005 and 2015, annual testing rates increased from 0.6/1000 person-years (pys) (95% confidence interval [CI] = 0.4 to 0.7/1000 pys) to 0.8/1000 pys (95% CI = 0.6 to 1.0/1000 pys) in women without incident breast or ovarian cancers. Rates decreased from 71.5/1000 pys (95% CI = 42.4 to 120.8/1000 pys) to 44.4/1000 pys (95% CI = 35.5 to 55.6/1000 pys) in women with incident diagnoses, despite improvements in provision of timely BRCA testing during this time frame. We found no evidence of secular trends in clinically eligible subgroups including women with family history indicating increased hereditary cancer risk, but no personal cancer history. At the end of the study period, 97.0% (95% CI = 96.6% to 97.3%) of these women remained untested.

Conclusion: Many eligible women did not receive BRCA testing despite having insurance coverage and access to specialty genetic services, underscoring challenges to primary and secondary hereditary cancer prevention.
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http://dx.doi.org/10.1093/jnci/djz008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6695306PMC
August 2019

Population-Based Assessment of the Association Between Magnetic Resonance Imaging Background Parenchymal Enhancement and Future Primary Breast Cancer Risk.

J Clin Oncol 2019 04 9;37(12):954-963. Epub 2019 Jan 9.

2 University of California, San Francisco, San Francisco, CA.

Purpose: To evaluate comparative associations of breast magnetic resonance imaging (MRI) background parenchymal enhancement (BPE) and mammographic breast density with subsequent breast cancer risk.

Patients And Methods: We examined women undergoing breast MRI in the Breast Cancer Surveillance Consortium from 2005 to 2015 (with one exam in 2000) using qualitative BPE assessments of minimal, mild, moderate, or marked. Breast density was assessed on mammography performed within 5 years of MRI. Among women diagnosed with breast cancer, the first BPE assessment was included if it was more than 3 months before their first diagnosis. Breast cancer risk associated with BPE was estimated using Cox proportional hazards regression.

Results: Among 4,247 women, 176 developed breast cancer (invasive, n = 129; ductal carcinoma in situ,n = 47) over a median follow-up time of 2.8 years. More women with cancer had mild, moderate, or marked BPE than women without cancer (80% 66%, respectively). Compared with minimal BPE, increasing BPE levels were associated with significantly increased cancer risk (mild: hazard ratio [HR], 1.80; 95% CI, 1.12 to 2.87; moderate: HR, 2.42; 95% CI, 1.51 to 3.86; and marked: HR, 3.41; 95% CI, 2.05 to 5.66). Compared with women with minimal BPE and almost entirely fatty or scattered fibroglandular breast density, women with mild, moderate, or marked BPE demonstrated elevated cancer risk if they had almost entirely fatty or scattered fibroglandular breast density (HR, 2.30; 95% CI, 1.19 to 4.46) or heterogeneous or extremely dense breasts (HR, 2.61; 95% CI, 1.44 to 4.72), with no significant interaction ( = .82). Combined mild, moderate, and marked BPE demonstrated significantly increased risk of invasive cancer (HR, 2.73; 95% CI, 1.66 to 4.49) but not ductal carcinoma in situ (HR, 1.48; 95% CI, 0.72 to 3.05).

Conclusion: BPE is associated with future invasive breast cancer risk independent of breast density. BPE should be considered for risk prediction models for women undergoing breast MRI.
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http://dx.doi.org/10.1200/JCO.18.00378DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6494266PMC
April 2019

Understanding Patients' Perspectives and Information Needs Following a Positive Home Human Papillomavirus Self-Sampling Kit Result.

J Womens Health (Larchmt) 2019 03 27;28(3):384-392. Epub 2018 Nov 27.

3 Kaiser Permanente Washington Health Research Institute , Seattle, Washington.

Objective: We explored patient perspectives after a positive human papillomavirus (HPV) self-sampling result to describe experiences and information needs for this home-based screening modality.

Materials And Methods: We recruited women who tested high-risk (hr) HPV positive during a pragmatic trial evaluating mailed hrHPV self-sampling kits as an outreach strategy for women overdue for Pap screening in a U.S. integrated health care system. Telephone interviews were conducted from 2014 to 2017. Five independent coders analyzed transcripts using iterative content analysis.

Results: Forty-six women (61% of invited; median age 55.5 years) completed a semistructured interview. Six themes emerged: (1) convenience of home-based screening, (2) intense feelings and emotions after receiving positive kit results, (3) importance of seeing provider and discussing kit results, (4) information seeking from various sources, (5) confusion about purpose and meaning of HPV versus Pap tests, and (6) concern that HPV self-sampling is inaccurate when the subsequent Pap test is normal.

Conclusions: Although women liked the kit's convenience, discussion about discordant home HPV and in-clinic Pap results led them to question the accuracy of HPV self-sampling. Patient-provider communication around home HPV kits is more complex than for reflex or cotesting because clinician-collected Pap results are unknown at the time of the positive kit result. Patients need education about differences between HPV and Pap tests and how they are used for screening and follow-up. To reassure patients and keep them interested in self-sampling, education should be provided at multiple time points during the screening process.
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http://dx.doi.org/10.1089/jwh.2018.7070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6444912PMC
March 2019

Competing Risks for a Diagnosis of Invasive Breast Cancer-Reply.

JAMA Oncol 2019 01;5(1):111

Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, United Kingdom.

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http://dx.doi.org/10.1001/jamaoncol.2018.5102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7098814PMC
January 2019

Primary care physician resource use changes associated with feedback reports.

Am J Manag Care 2018 10;24(10):455-461

RTI International, 307 Waverly Oaks Rd, Ste 101, Waltham, MA 02452. Email:

Objectives: To measure changes in primary care physician (PCP) ordering rates for 4 global resource use measures before and after dissemination of physician feedback reports that provided peer-comparison resource use rates. We also explored whether physician practice characteristics (panel size, clinic size, and years of experience) were associated with resource use changes.

Study Design: Pre-post implementation study measuring physician resource use in an integrated healthcare system (2011-2014).

Methods: Kaiser Permanente Washington PCPs (N = 210) were provided annual feedback reports showing their personal ordering rates compared with those of their peers. Monthly physician ordering was measured from November 2011 to September 2014 (including prereport and postreport periods). We examined 4 physician ordering rates (specialty referrals, high-end imaging, laboratory tests, and 30-day prescriptions) per 1000 patients, adjusted for patient age, gender, and clinical complexity.

Results: After accounting for physician practice characteristics, monthly PCP ordering rates for high-end imaging significantly decreased by 0.8 images per 1000 patients (P <.01). In contrast, orders for laboratory tests and 30-day prescriptions significantly increased by 15.0 tests and 84.7 prescriptions per 1000 patients (both P <.01). We observed greater changes following feedback in physicians with fewer years of experience (≤10 years), who had 4.2 fewer specialty referrals (P = .01) and 101.3 more 30-day prescriptions (P <.01) compared with those with more experience (>20 years).

Conclusions: Physician feedback reports may be associated with changes in physician resource use, and physicians with fewer years of experience may be more responsive to feedback reports. Better understanding of factors associated with changes in resource use is necessary for future targeted development of physician interventions.
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October 2018

A qualitative study exploring patient motivations for screening for lung cancer.

PLoS One 2018 5;13(7):e0196758. Epub 2018 Jul 5.

Kaiser Permanente Washington Health Research Institute, Kaiser Permanente Washington, Seattle, Washington, United States of America.

Background: Low-dose computed tomography (LDCT) of the chest for lung cancer screening of heavy smokers was given a 'B' rating by the U.S. Preventive Services Task Force (USPSTF) in 2013, and gained widespread insurance coverage in the U.S. in 2015. Lung cancer screening has since had low uptake. However, for those that do choose to screen, little is known about patient motivations for completing screening in real-world practice.

Objective: To explore the motivations for screening-eligible patients to screen for lung cancer.

Methods: Semi-structured qualitative interviews were conducted with 20 LDCT screen-completed men and women who were members of an integrated mixed-model healthcare system in Washington State. From June to September 2015, participants were recruited and individual interviews performed about motivations to screen for lung cancer. Audio-recorded interviews were transcribed and analyzed using inductive content analysis by three investigators.

Results: Four primary themes emerged as motivations for completing LDCT lung cancer screening: 1) trust in the referring clinician; 2) early-detection benefit; 3) low or limited harm perception; and 4) friends or family with advanced cancer.

Conclusion: Participants in our study were primarily motivated to screen for lung cancer based on perceived benefit of early-detection, absence of safety concerns, and personal relationships. Our findings provide new insights about patient motivations to screen, and can potentially be used to improve lung cancer screening uptake and shared decision-making processes.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0196758PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6033377PMC
December 2018

Cumulative Risk Distribution for Interval Invasive Second Breast Cancers After Negative Surveillance Mammography.

J Clin Oncol 2018 07 2;36(20):2070-2077. Epub 2018 May 2.

Janie M. Lee and Diana L. Lam, University of Washington, and Seattle Cancer Care Alliance; Linn Abraham, Diana S.M. Buist, and Diana L. Miglioretti, Kaiser Permanente Washington Health Research Institute, Seattle, WA; Karla Kerlikowske, Department of Veterans Affairs, University of California, San Francisco, San Francisco; Diana L. Miglioretti, University of California, Davis, Davis, CA; Nehmat Houssami, University of Sydney, Sydney, New South Wales, Australia; Constance D. Lehman, Massachusetts General Hospital, Boston, MA; Louise M. Henderson, University of North Carolina, Chapel Hill, Chapel Hill, NC; and Rebecca A. Hubbard, University of Pennsylvania, Philadelphia, PA.

Purpose The aim of the current study was to characterize the risk of interval invasive second breast cancers within 5 years of primary breast cancer treatment. Methods We examined 65,084 surveillance mammograms from 18,366 women with a primary breast cancer diagnosis of unilateral ductal carcinoma in situ or stage I to III invasive breast carcinoma performed from 1996 to 2012 in the Breast Cancer Surveillance Consortium. Interval invasive breast cancer was defined as ipsilateral or contralateral cancer diagnosed within 1 year after a negative surveillance mammogram. Discrete-time survival models-adjusted for all covariates-were used to estimate the probability of interval invasive cancer, given the risk factors for each surveillance round, and aggregated across rounds to estimate the 5-year cumulative probability of interval invasive cancer. Results We observed 474 surveillance-detected cancers-334 invasive and 140 ductal carcinoma in situ-and 186 interval invasive cancers which yielded a cancer detection rate of 7.3 per 1,000 examinations (95% CI, 6.6 to 8.0) and an interval invasive cancer rate of 2.9 per 1,000 examinations (95% CI, 2.5 to 3.3). Median cumulative 5-year interval cancer risk was 1.4% (interquartile range, 0.8% to 2.3%; 10 to 90th percentile range, 0.5% to 3.7%), and 15% of women had ≥ 3% 5-year interval invasive cancer risk. Cumulative 5-year interval cancer risk was highest for women with estrogen receptor- and progesterone receptor-negative primary breast cancer (2.6%; 95% CI, 1.7% to 3.5%), interval cancer presentation at primary diagnosis (2.2%; 95% CI, 1.5% to 2.9%), and breast conservation without radiation (1.8%; 95% CI, 1.1% to 2.4%). Conclusion Risk of interval invasive second breast cancer varies across women and is influenced by characteristics that can be measured at initial diagnosis, treatment, and imaging. Risk prediction models that evaluate the risk of cancers not detected by surveillance mammography should be developed to inform discussions of tailored surveillance.
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http://dx.doi.org/10.1200/JCO.2017.76.8267DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6036621PMC
July 2018