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Background: Clinical trials demonstrated that women treated for breast cancer with anthracycline or trastuzumab are at increased risk for heart failure and/or cardiomyopathy (HF/CM), but the generalizability of these findings is unknown. We estimated real-world adjuvant anthracycline and trastuzumab use and their associations with incident HF/CM.Methods: We conducted a population-based, retrospective cohort study of 12,500 women diagnosed with incident, invasive breast cancer from January 1, 1999 through December 31, 2007, at eight integrated Cancer Research Network health systems. Using administrative procedure and pharmacy codes, we identified anthracycline, trastuzumab, and other chemotherapy use. We identified incident HF/CM following chemotherapy initiation and assessed risk of HF/CM with time-varying chemotherapy exposures vs no chemotherapy. Multivariable Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) with adjustment for age at diagnosis, stage, Cancer Research Network site, year of diagnosis, radiation therapy, and comorbidities.Results: Among 12 500 women (mean age = 60 years, range = 22-99 years), 29.6% received anthracycline alone, 0.9% received trastuzumab alone, 3.5% received anthracycline plus trastuzumab, 19.5% received other chemotherapy, and 46.5% received no chemotherapy. Anthracycline and trastuzumab recipients were younger, with fewer comorbidities than recipients of other chemotherapy or none. Compared with no chemotherapy, the risk of HF/CM was higher in patients treated with anthracycline alone (adjusted HR = 1.40, 95% CI = 1.11 to 1.76), although the increased risk was similar to other chemotherapy (adjusted HR = 1.49, 95% CI = 1.25 to 1.77); the risk was highly increased in patients treated with trastuzumab alone (adjusted HR = 4.12, 95% CI = 2.30 to 7.42) or anthracycline plus trastuzumab (adjusted HR = 7.19, 95% CI = 5.00 to 10.35).Conclusions: Anthracycline and trastuzumab were primarily used in younger, healthier women and associated with increased HF/CM risk compared with no chemotherapy. This population-based observational study complements findings from clinical trials on cancer treatment safety. [ABSTRACT FROM AUTHOR]

Rationale and Objectives: To examine the feasibility of and satisfaction with a tailored web-based intervention designed to decrease radiologists' recommendation of inappropriate additional work-up after a screening mammogram.Materials and Methods: We developed a web-based educational intervention designed to reduce inappropriate recall. Radiologists were randomly assigned to participate in an early intervention group or a late (control) intervention group, the latter of which served as a control for a 9-month follow-up period, after which they were invited to participate in the intervention. Intervention content was derived from our prior research and included three modules: 1) an introduction to audit statistics for mammography performance; 2) a review of data showing radiologists' inflated perceptions of medical malpractice risks related to breast imaging, and 3) a review of data on breast cancer risk among women seen in their practices. Embedded within the intervention were individualized audit data for each participating radiologists obtained from the national Breast Cancer Surveillance Consortium.Results: Seventy-four radiologists (37.8%; 74/196) consented to the intervention, which was completed by 67.5% (27/40) of those randomized to the early intervention group and 41.2% (14/34) of those randomized to the late (control) group. Thus, a total of 41 (55%) completed the intervention. On average, three log-ins were used to complete the program (range 1-14), which took approximately 1 hour. Ninety-five percent found the program moderately to very helpful in understanding how to calculate basic performance measures. Ninety-three percent found viewing their own performance measures moderately to very helpful, and 83% reported it being moderately to very important to learn that the breast cancer risk in their screening population program was lower than perceived. The percentage of radiologists who reported that the risk of medical malpractice influences their recall rates dropped from 36.3% preintervention to 17.8% after intervention with a similar drop in perceived influence of malpractice risk on their recommendations for breast biopsy (36.4 to 17.3%). More than 75% of radiologists answered the postintervention knowledge questions correctly, and the percent of time spent in breast imaging did not appear to influence responses. The majority (>92%) of participants correctly responded that the target recall rate in the United States is 9%. The mean self-reported recall rates were 13.0 for radiologists spending <40% time in breast imaging and 14.9% for those spending >40% time spent in breast imaging, which was highly correlated with their actual recall rates (0.991; P < .001).Conclusions: Radiologists who begin an internet-based tailored intervention designed to help reduce unnecessary recall will likely complete it, although only 55% who consented to the study actually undertook the intervention. Participants found the program useful in helping them understand why their recall rates may be elevated. [ABSTRACT FROM AUTHOR]

Background: Without population-based evidence, some clinicians recommend short-term suspension of hormone therapy to improve the performance of mammography. Hormone therapy increases breast density, and abnormal screening mammograms are more common among women with denser breasts and among women using hormone therapy.Objective: To test whether 1 to 2 months of hormone therapy suspension before screening mammography decreases additional mammographic imaging (recall) in women age 45 to 80 years.Design: 3-group randomized, controlled trial.Setting: Integrated health plan in western Washington from 2004 to 2007.Patients: 1704 women age 45 to 80 years who used hormone therapy at their most recent screening (index) mammography, were due for screening (study) mammography, and were still using hormone therapy.Intervention: Block random assignment (by breast density and hormone therapy type) to no hormone therapy suspension (n = 567) or suspension for 1 month (n = 570) or 2 months (n = 567) before study mammography. One blinded expert radiologist interpreted all mammograms.Measurements: Recall was the primary outcome, and change in mammographic breast density (percentage and dense area) between the index and study mammograms was the secondary outcome.Results: Mammography recall rates were 11.3% (61 of 542 women in the no-suspension group), 12.3% (50 of 478 women in the 1-month suspension group), and 9.8% (44 of 451 women in the 2-month suspension group). No subgroups were identified in which brief suspension of hormone therapy resulted in decreased mammography recall. With suspension, decreases in percentage of breast density were orderly and statistically significant: 0.1% (no-suspension group), -0.9% (1-month suspension group), and -1.5% (2-month suspension group). Similar ordered decreases were observed for dense area. Women in the suspension groups experienced increased menopause symptoms.Limitations: Results can only be generalized to women age 45 to 80 years who have used hormone therapy for at least 1 year and will consider short-term suspension; most eligible women (61%) declined participation. Mammography recall was determined by 1 expert radiologist.Conclusion: Brief hormone therapy suspension was associated with small changes in breast density and did not affect recall rates. No evidence supports short-term hormone therapy suspension before mammography. [ABSTRACT FROM AUTHOR]

Purpose: The National Comprehensive Cancer Network (NCCN) guidelines recommend a variety of drug combinations with specific administration schedules for the treatment of early-stage breast cancer, allowing physicians to deliver treatments recognizing individual patient complexities, including comorbidities, and patient-physician preference. While use of guideline regimens has shifted over time, there is little data to describe changes in how treatment for early-stage breast cancer has evolved over time., Methods: In a cohort of 34,109 women treated for stage I-IIIA breast cancer between 2006-2019 at Kaiser Permanente Northern California and Kaiser Permanente Washington, we present the changes in chemotherapy regimens over time, and explore use of NCCN-guideline regimens (GR), guideline regimens used when said regimens were not included in guidelines, referred to as time-discordant regimens (TDR), and non-guideline regimens (NGR). Results are presented by drug combination and over time., Results: Among 12,506 women receiving chemotherapy, 77.4% (n = 9681) received GRs, 9.1% (n = 1140) received TDRs, and 13.5% (n = 1685) received NGRs. In 2006, AC-T (cyclophosphamide-doxorubicin, paclitaxel) was the most common regimen, with TC (cyclophosphamide-docetaxel) becoming the most prevalent by 2019. NGRs were more common in cyclophosphamide-methotrexate-5-fluorouracil (CMF); cyclophosphamide-doxorubicin-paclitaxel-trastuzumab (ACTH); and paclitaxel-trastuzumab (TH). The use of GR has increased over time (p-trend < 0.001), while use of NGR (both in terms of administration schedule and drug combination) and TDR have decreased, although patterns vary by drug combination., Conclusion: Chemotherapy delivery has changed markedly over time, with a move toward more use of GR. These data are important for understanding the landscape of chemotherapy delivery in community healthcare settings., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Guidelines informing chemotherapy regimen selection are based on clinical trials with participants who do not necessarily represent general populations with breast cancer. Understanding who receives nonguideline regimens is important for understanding real-world chemotherapy administration and how it relates to patient outcomes., Methods: Using data from the Optimal Breast Cancer Chemotherapy Dosing (OBCD) study, based at Kaiser Permanente Northern California (2006-2019) and Kaiser Permanente Washington (2004-2015), we use logistic regression to examine the associations between patient characteristics and receipt of nonguideline chemotherapy regimens among 11,293 women with primary stage I to IIIA breast cancer receiving chemotherapy., Results: The use of nonguideline regimens was strongly associated with several factors, including older age [≥80 vs. 18-39 years: OR, 5.25; 95% confidence interval (CI), 3.06-9.00; P-trend = 0.002] and HER2 status (HER2+ vs. HER2-: OR, 3.44; 95% CI, 3.06-3.87) and was less likely in women with larger tumor size (>5 cm vs. 0.1 to ≤0.5 cm: OR, 0.56; 95% CI, 0.36-0.87; P-trend = 0.01) and diagnosed in later years (2012-2019 vs. 2005-2011: OR, 0.80; 95% CI, 0.71-0.90). Factors associated varied by type of nonguideline regimens. For example, women with comorbidity and older age were more likely to receive nonguideline drug combinations in particular, whereas women with larger tumor size were less likely to receive nonguideline administration schedules., Conclusions: Nonguideline chemotherapy regimens are more likely in certain patient populations., Impact: These associations highlight that vulnerable patient populations may be less likely to receive guideline care, and thus, real-world studies are essential for understanding how the use of nonguideline regimens impacts patient outcomes in these groups., (©2024 American Association for Cancer Research.)

Objectives: Chronic kidney disease (CKD) affects up to 11% of the population. General practice is at the forefront of the identification of patients with declining kidney function, and appropriate monitoring and management of patients with CKD. An individualized and patient-centred approach is currently recommended in guidelines, but would be enhanced by more detailed guidance on how this should be applied to different age groups, such as use of a kidney trajectory chart. We explored the opinion of general practitioners (GPs) about the potential utility of kidney trajectory charts., Methods: Qualitative study interviewing 27 Australian GPs about their management of chronic kidney disease. GPs were presented with charts that plotted percentiles of kidney function (eGFR) with age and discussed how they would use the charts manage to patients with declining kidney function. GPs' opinion was sought as to how useful these charts might be in clinical practice., Results: Most GPs were positive about the use of kidney trajectory charts to assist them with recognition and management of declining kidney function in general practice: e.g, comments included a "valuable tool", "a bit of an eye opener"," will help me explain to the patients", "I'll stick it on my wall.". GPs responded that the charts could help monitor patients, trigger early recognition of a younger patient at risk, and assist with older patients to determine when treatment may not be warranted. GPs also thought that charts could also be useful to motivate patients and help them monitor their own condition., Conclusions: Use of percentile charts in conjunction with the current CKD guidelines help support a patient-centred model of care. Kidney trajectory charts can help patients to understand their risk of further kidney damage or decline. Research on the use of these charts in clinical practice should be undertaken to further develop their use., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests- Paul Glasziou and Jenny Doust report grants from the Australian National Health and Medical Research Council during the period of this study. Michelle Guppy, Paul Glasziou, and Jenny Doust received a grant from the Royal Australian College of General Practitioners Foundation to undertake this research. Joy Bowles was paid as a research assistant through this grant. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Guppy et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Chronic kidney disease (CKD) is commonly managed in general practice, with established guidelines for diagnosis and management. CKD is more prevalent in the older population, and is associated with lifestyle diseases as well as social deprivation. Older patients also commonly experience multimorbidity. Current CKD guidelines do not take age into account, with the same diagnostic and management recommendations for patients regardless of their age. We sought to investigate general practitioners' (GPs') approach to older patients with CKD, and whether their assessment and management differed from guideline recommendations. We explored the reasons for variation from guideline recommendations., Methods: This was a mixed methods study of Australian GPs. An online anonymous survey about the use of CKD guidelines, and assessment and management of CKD was sent to 9500 GPs. Four hundred and sixty-nine (5%) of GPs responded, and the survey was completed by 399 GPs. Subsequently, 27 GPs were interviewed in detail about their diagnostic and management approach to older patients with declining kidney function., Results: In the survey, 48% of GPs who responded found the CKD guidelines useful for diagnosis and management. Four themes arose from our interviews: age-related decline in kidney function; whole person care; patient-centred care; and process of care that highlighted the importance of continuity of care. GPs recognised that older patients have an inherently high risk of lower kidney function. The GPs reported management of that higher risk focused on managing the whole person (not just a single disease focus) and being patient-centred. Patient-centred care expressed the importance of quality of life, shared decision making and being symptom focused. There was also a recognition that there is a difference between a sudden decline in kidney function and a stable but low kidney function and GPs would manage these situations differently., Conclusions: GPs apply guidelines in the management of CKD in older patients using a patient-centred and whole person approach to care. Older patients have a high prevalence of multimorbidity, which GPs carefully considered when applying existing CKD-specific guidelines. Future iterations of CKD Guidelines need to give due consideration to multimorbidity in older patients that can adversely impact on kidney function in addition to the expected age-related functional decline., (© 2024. The Author(s).)

Background: Guidelines for terminology defining chronic kidney disease (CKD) have been in use for 20 years. Age is not currently considered in the guideline definition of CKD. In previous studies, General Practitioners (GPs) have been reluctant to give older patients the label of CKD., Aim: Our study aimed to determine what language general practitioners are using to describe or label chronic kidney disease with their older patients, and to explore the reasons for their use of alternative language., Design & Setting: This was a descriptive qualitative interview study of Australian GPs., Method: Twenty-seven GPs were recruited via email and interviewed regarding their management of CKD., GPs were asked what language and terminology they used when discussing a diagnosis of CKD with their older patients., Results: "Labelling of CKD", the language that GPs use when talking about CKD with their patients, emerged as a major theme from the initial GP interviews. Sub-themes emerged, including: types of labels, alternate labels and rationale for alternate labelling. GPs used descriptions of "reduced kidney function" to explain CKD to their patients, either in parallel with the diagnosis of CKD or instead of it. GPs had concerns about the words "chronic" and "disease" and used different terminology to explain these words to patients when diagnosing them with CKD., Conclusion: GPs use alternative descriptions to explain mild decrease in kidney function with older patients. Alternative labels that denote level of risk to older patients, without creating unnecessary concern about normal age-related kidney function need to be explored., (Copyright © 2024, The Authors.)

Introduction: Reporting of aromatherapy-focused research often lacks sufficient quality and detail for replication and subsequent application of results. To our knowledge currently, no quality appraisal tool exists for aromatherapy research reporting. To address this gap, the Aromatic Research Quality Appraisal Taskforce (ARQAT) composed of aromatherapy professionals with varied expert backgrounds came together. Presented here is the Transparent Reporting for Essential oil and Aroma Therapeutic Studies (TREATS) checklist, which is a result of this collaborative effort. Methods: Creation of TREATS followed a three-stage process, including determination of interest/need, development, and dissemination. The shortcomings of existing aromatherapy research reporting quality were evaluated and responses to address these shortcomings were used to create checklist items that were then grouped into sections. Items for each section were brain-stormed with reference to the aromatherapy literature and ARQAT's expert knowledge, and the development of each section followed an iterative process until agreement was reached. An explanatory document was also created to assist more accurate use of the tool; it and the checklist were reviewed by a group of aromatherapy experts. Results: The TREATS checklist with 38 items in four sections was developed along with the explanatory document. The ARQAT and a global group of aromatherapy experts reviewed the TREATS. Their results and comments assisted development of the current version. The TREATS identifies key components of research involving essential oils, their application, and olfactory considerations that ARQAT considers the minimum necessary for high-quality aromatherapy research. Conclusion: The TREATS, explanatory document, and associated website (www.arqat.org) contribute to thorough aromatherapy research critique. The TREATS checklist aids appraisal of quality and can be used with any study design. It lays the foundation for the future development of aromatic research reporting guidelines.

Previous studies demonstrate that self-reports of mammography screening for breast cancer and colonoscopy screening for colorectal cancer demonstrate concordance, based on adherence to screening guidelines, with electronic medical records (EMRs) in over 90% of those interviewed, as well as high sensitivity and specificity, and can be used for monitoring our Healthy People goals. However, for screening tests for cervical and lung cancers, and for various sub-populations, concordance between self-report and EMRs has been noticeably lower with poor sensitivity or specificity. This study aims to test the validity and reliability of lung, colorectal, cervical, and breast cancer screening questions from the 2021 and 2022 National Health Interview Survey (NHIS). We present the protocol for a study designed to measure the validity and reliability of the NHIS cancer screening questions compared to EMRs from four US-based healthcare systems. We planned a randomized trial of a phone- vs web-based survey with NHIS questions that were previously revised based on extensive cognitive interviewing. Our planned sample size will be 1576 validity interviews, and 1260 interviews randomly assigned at 1 or 3 months after the initial interview. We are enrolling people eligible for cancer screening based on age, sex, and smoking history per US Preventive Services Task Force recommendations. We will evaluate question validity using concordance, sensitivity, specificity, positive predictive value, negative predictive value, and report-to-records ratio. We further are randomizing participants to complete a second survey 1 vs 3 months later to assess question reliability. We suggest that typical measures of concordance may need to be reconsidered in evaluating cancer screening questions., Competing Interests: None., (Copyright: © 2024 Kessler et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: We updated algorithms to identify breast cancer recurrences from administrative data, extending previously developed methods., Methods: In this validation study, we evaluated pairs of breast cancer recurrence algorithms (vs. individual algorithms) to identify recurrences. We generated algorithm combinations that categorized discordant algorithm results as no recurrence [High Specificity and PPV (positive predictive value) Combination] or recurrence (High Sensitivity Combination). We compared individual and combined algorithm results to manually abstracted recurrence outcomes from a sample of 600 people with incident stage I-IIIA breast cancer diagnosed between 2004 and 2015. We used Cox regression to evaluate risk factors associated with age- and stage-adjusted recurrence rates using different recurrence definitions, weighted by inverse sampling probabilities., Results: Among 600 people, we identified 117 recurrences using the High Specificity and PPV Combination, 505 using the High Sensitivity Combination, and 118 using manual abstraction. The High Specificity and PPV Combination had good specificity [98%, 95% confidence interval (CI): 97-99] and PPV (72%, 95% CI: 63-80) but modest sensitivity (64%, 95% CI: 44-80). The High Sensitivity Combination had good sensitivity (80%, 95% CI: 49-94) and specificity (83%, 95% CI: 80-86) but low PPV (29%, 95% CI: 25-34). Recurrence rates using combined algorithms were similar in magnitude for most risk factors., Conclusions: By combining algorithms, we identified breast cancer recurrences with greater PPV than individual algorithms, without additional review of discordant records., Impact: Researchers should consider tradeoffs between accuracy and manual chart abstraction resources when using previously developed algorithms. We provided guidance for future studies that use breast cancer recurrence algorithms with or without supplemental manual chart abstraction., (©2023 American Association for Cancer Research.)

Purpose: Most cytotoxic drugs are dosed using body surface area (BSA), yet not all cancer patients receive the full BSA-determined dose. Prior work suggests that breast cancer patients who are obese are more likely to experience dose reduction than normal weight patients. However, the factors driving dose reduction remain unclear., Methods: In 452 women diagnosed with stage I-IIIA primary breast cancer at Kaiser Permanente Northern California, we evaluated the association between obesity and dose reduction, and further explored other factors in relation to dose reduction, including various sociodemographic characteristics, tumor characteristics, and comorbidities. Study participants were a part of the Pathways Study, diagnosed between 2006 and 2013 and treated with cyclophosphamide + doxorubicin, followed by paclitaxel (ACT). Dose reduction was assessed using first cycle dose proportion (FCDP) and average relative dose intensity (ARDI), a metric of dose intensity over the course of chemotherapy., Results: Overall, 8% of participants received a FCDP < 90% and 21.2% had an ARDI < 90%, with dose reduction increasing with body mass index. In adjusted logistic regression models, obese women had 4.1-fold higher odds of receiving an ARDI < 90% than normal weight women (95% CI: 1.9-8.9; p-trend = 0.0006). Increasing age was positively associated with an ADRI < 90%, as was the presence of comorbidity. Dose reduction was less common in later calendar years., Conclusion: Results offer insight on factors associated with chemotherapy dosing for a common breast cancer regimen. Larger studies are required to evaluate relevance to other regimens, and further work will be needed to determine whether dose reductions impact outcomes in obese women., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Women with dense breasts have an increased risk of breast cancer. However, breast density is measured with variability, which may reduce the reliability and accuracy of its association with breast cancer risk. This is particularly relevant when visually assessing breast density due to variation in inter- and intra-reader assessments. To address this issue, we developed a longitudinal breast density measure which uses an individual woman's entire history of mammographic density, and we evaluated its association with breast cancer risk as well as its predictive ability., Methods: In total, 132,439 women, aged 40-73 yr, who were enrolled in Kaiser Permanente Washington and had multiple screening mammograms taken between 1996 and 2013 were followed up for invasive breast cancer through 2014. Breast Imaging Reporting and Data System (BI-RADS) density was assessed at each screen. Continuous and derived categorical longitudinal density measures were developed using a linear mixed model that allowed for longitudinal density to be updated at each screen. Predictive ability was assessed using (1) age and body mass index-adjusted hazard ratios (HR) for breast density (time-varying covariate), (2) likelihood-ratio statistics (ΔLR-χ 2 ) and (3) concordance indices., Results: In total, 2704 invasive breast cancers were diagnosed during follow-up (median = 5.2 yr; median mammograms per woman = 3). When compared with an age- and body mass index-only model, the gain in statistical information provided by the continuous longitudinal density measure was 23% greater than that provided by BI-RADS density (follow-up after baseline mammogram: ΔLR-χ 2  = 379.6 (degrees of freedom (df) = 2) vs. 307.7 (df = 3)), which increased to 35% (ΔLR-χ 2  = 251.2 vs. 186.7) for follow-up after three mammograms (n = 76,313, 2169 cancers). There was a sixfold difference in observed risk between densest and fattiest eight-category longitudinal density (HR = 6.3, 95% CI 4.7-8.7), versus a fourfold difference with BI-RADS density (HR = 4.3, 95% CI 3.4-5.5). Discriminatory accuracy was marginally greater for longitudinal versus BI-RADS density (c-index = 0.64 vs. 0.63, mean difference = 0.008, 95% CI 0.003-0.012)., Conclusions: Estimating mammographic density using a woman's history of breast density is likely to be more reliable than using the most recent observation only, which may lead to more reliable and accurate estimates of individual breast cancer risk. Longitudinal breast density has the potential to improve personal breast cancer risk estimation in women attending mammography screening., (© 2023. The Author(s).)

Background: We evaluated diagnostic mammography among women with a breast lump to determine whether performance varied across racial and ethnic groups., Methods: This study included 51,014 diagnostic mammograms performed between 2005 and 2018 in the Breast Cancer Surveillance Consortium among Asian/Pacific Islander (12%), Black (7%), Hispanic/Latina (6%), and White (75%) women reporting a lump. Breast cancers occurring within 1 year were ascertained from cancer registry linkages. Multivariable regression was used to adjust performance statistic comparisons for breast cancer risk factors, mammogram modality, demographics, additional imaging, and imaging facility., Results: Cancer detection rates were highest among Asian/Pacific Islander [per 1,000 exams, 84.2 (95% confidence interval (CI): 72.0-98.2)] and Black women [81.4 (95% CI: 69.4-95.2)] and lowest among Hispanic/Latina women [42.9 (95% CI: 34.2-53.6)]. Positive predictive values (PPV) were higher among Black [37.0% (95% CI: 31.2-43.3)] and White [37.0% (95% CI: 30.0-44.6)] women and lowest among Hispanic/Latina women [22.0% (95% CI: 17.2-27.7)]. False-positive results were most common among Asian/Pacific Islander women [per 1,000 exams, 183.9 (95% CI: 126.7-259.2)] and lowest among White women [112.4 (95% CI: 86.1-145.5)]. After adjustment, false-positive and cancer detection rates remained higher for Asian/Pacific Islander and Black women (vs. Hispanic/Latina and White). Adjusted PPV was highest among Asian/Pacific Islander women., Conclusions: Among women with a lump, Asian/Pacific Islander and Black women were more likely to have cancer detected and more likely to receive a false-positive result compared with White and Hispanic/Latina women., Impact: Strategies for optimizing diagnostic mammography among women with a lump may vary by racial/ethnic group, but additional factors that influence performance differences need to be identified. See related In the Spotlight, p. 1479., (©2023 American Association for Cancer Research.)

Background: Breast cancer survivors are living longer due to early detection and advances in treatment and are at increased risk for second primary cancers. Comprehensive evaluation of second cancer risk among patients treated in recent decades is lacking., Methods: We identified 16,004 females diagnosed with a first primary stage I-III breast cancer between 1990 and 2016 (followed through 2017) and survived ≥ 1 year at Kaiser Permanente (KP) Colorado, Northwest, and Washington. Second cancer was defined as an invasive primary cancer diagnosed ≥ 12 months after the first primary breast cancer. Second cancer risk was evaluated for all cancers (excluding ipsilateral breast cancer) using standardized incidence ratios (SIRs), and a competing risk approach for cumulative incidence and hazard ratios (HRs) adjusted for KP center, treatment, age, and year of first cancer diagnosis., Results: Over a median follow-up of 6.2 years, 1,562 women developed second cancer. Breast cancer survivors had a 70% higher risk of any cancer (95%CI = 1.62-1.79) and 45% higher risk of non-breast cancer (95%CI = 1.37-1.54) compared with the general population. SIRs were highest for malignancies of the peritoneum (SIR = 3.44, 95%CI = 1.65-6.33), soft tissue (SIR = 3.32, 95%CI = 2.51-4.30), contralateral breast (SIR = 3.10, 95%CI = 2.82-3.40), and acute myeloid leukemia (SIR = 2.11, 95%CI = 1.18-3.48)/myelodysplastic syndrome (SIR = 3.25, 95%CI = 1.89-5.20). Women also had elevated risks for oral, colon, pancreas, lung, and uterine corpus cancer, melanoma, and non-Hodgkin lymphoma (SIR range = 1.31-1.97). Radiotherapy was associated with increased risk for all second cancers (HR = 1.13, 95%CI = 1.01-1.25) and soft tissue sarcoma (HR = 2.36, 95%CI = 1.17-4.78), chemotherapy with decreased risk for all second cancers (HR = 0.87, 95%CI = 0.78-0.98) and increased myelodysplastic syndrome risk (HR = 3.01, 95%CI = 1.01-8.94), and endocrine therapy with lower contralateral breast cancer risk (HR = 0.48, 95%CI = 0.38-0.60). Approximately 1 in 9 women who survived ≥ 1 year developed second cancer, 1 in 13 developed second non-breast cancer, and 1 in 30 developed contralateral breast cancer by 10 years. Trends in cumulative incidence declined for contralateral breast cancer but not for second non-breast cancers., Conclusions: Elevated risks of second cancer among breast cancer survivors treated in recent decades suggests that heightened surveillance is warranted and continued efforts to reduce second cancers are needed., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Importance: Detection of ductal carcinoma in situ (DCIS) by mammography screening is a controversial outcome with potential benefits and harms. The association of mammography screening interval and woman's risk factors with the likelihood of DCIS detection after multiple screening rounds is poorly understood., Objective: To develop a 6-year risk prediction model for screen-detected DCIS according to mammography screening interval and women's risk factors., Design, Setting, and Participants: This Breast Cancer Surveillance Consortium cohort study assessed women aged 40 to 74 years undergoing mammography screening (digital mammography or digital breast tomosynthesis) from January 1, 2005, to December 31, 2020, at breast imaging facilities within 6 geographically diverse registries of the consortium. Data were analyzed between February and June 2022., Exposures: Screening interval (annual, biennial, or triennial), age, menopausal status, race and ethnicity, family history of breast cancer, benign breast biopsy history, breast density, body mass index, age at first birth, and false-positive mammography history., Main Outcomes and Measures: Screen-detected DCIS defined as a DCIS diagnosis within 12 months after a positive screening mammography result, with no concurrent invasive disease., Results: A total of 916 931 women (median [IQR] age at baseline, 54 [46-62] years; 12% Asian, 9% Black, 5% Hispanic/Latina, 69% White, 2% other or multiple races, and 4% missing) met the eligibility criteria, with 3757 screen-detected DCIS diagnoses. Screening round-specific risk estimates from multivariable logistic regression were well calibrated (expected-observed ratio, 1.00; 95% CI, 0.97-1.03) with a cross-validated area under the receiver operating characteristic curve of 0.639 (95% CI, 0.630-0.648). Cumulative 6-year risk of screen-detected DCIS estimated from screening round-specific risk estimates, accounting for competing risks of death and invasive cancer, varied widely by all included risk factors. Cumulative 6-year screen-detected DCIS risk increased with age and shorter screening interval. Among women aged 40 to 49 years, the mean 6-year screen-detected DCIS risk was 0.30% (IQR, 0.21%-0.37%) for annual screening, 0.21% (IQR, 0.14%-0.26%) for biennial screening, and 0.17% (IQR, 0.12%-0.22%) for triennial screening. Among women aged 70 to 74 years, the mean cumulative risks were 0.58% (IQR, 0.41%-0.69%) after 6 annual screens, 0.40% (IQR, 0.28%-0.48%) for 3 biennial screens, and 0.33% (IQR, 0.23%-0.39%) after 2 triennial screens., Conclusions and Relevance: In this cohort study, 6-year screen-detected DCIS risk was higher with annual screening compared with biennial or triennial screening intervals. Estimates from the prediction model, along with risk estimates of other screening benefits and harms, could help inform policy makers' discussions of screening strategies.

Background: Soft tissue sarcoma is a rare but serious side-effect of radiotherapy to treat breast cancer, and rates are increasing in the USA. We evaluated potential co-factors in two complimentary cohorts of US breast cancer survivors., Methods: In this retrospective cohort study, we sourced data from the Kaiser Permanente (KP) cohort and the Surveillance, Epidemiology, and End Results (SEER) 13 registries cohort, both in the USA. The KP cohort included 15 940 women diagnosed with breast cancer from Jan 1, 1990, to Dec 31, 2016, in KP Colorado, KP Northwest (which serves Oregon and Southwest Washington state), or KP Washington, with detailed treatment data and comorbidities (including hypertension and diabetes at or before breast cancer diagnosis) from electronic medical records. The SEER cohort included 457 300 women diagnosed with breast cancer from Jan 1, 1992, to Dec 31, 2016, within the 13 SEER registries across the USA, with initial treatment data (yes vs no or unknown). Eligibility criteria in both cohorts were female breast cancer survivors (stage I-III) aged 20-84 years at diagnosis who had breast cancer surgery, and had survived at least 1 year after breast cancer diagnosis. The outcome of interest was any second thoracic soft tissue sarcoma (angiosarcomas and other subtypes) that developed at least 1 year after breast cancer diagnosis. Risk factors for thoracic soft tissue sarcoma were assessed using multivariable Poisson regression models., Findings: In the KP cohort, median follow-up was 9·3 years (IQR 5·7-13·9) and 19 (0·1%) of 15 940 eligible, evaluable women developed a thoracic soft tissue sarcoma (11 angiosarcomas, eight other subtypes). Most (94·7%; 18 of 19) thoracic soft tissue sarcomas occurred in women treated with radiotherapy; thus, radiotherapy was associated with a significantly increased risk of developing a thoracic soft tissue sarcoma (relative risk [RR] 8·1 [95% CI 1·1-60·4]; p=0·0052), but there was no association with prescribed dose, fractionation, or boost. The RR of angiosarcoma after anthracyclines was 3·6 (95% CI 1·0-13·3; p=0·058). Alkylating agents were associated with an increased risk of developing other sarcomas (RR 7·7 [95% CI 1·2-150·8]; p=0·026). History of hypertension (RR 4·8 [95% CI 1·3-17·6]; p=0·017) and diabetes (5·3 [1·4-20·8]; p=0·036) were each associated with around a five-times increased risk of angiosarcoma. In the SEER cohort, 430 (0·1%) of 457 300 patients had subsequent thoracic soft tissue sarcomas (268 angiosarcomas and 162 other subtypes) after a median follow-up of 8·3 years (IQR 4·3-13·9). Most (77·9%; 335 of 430) cases occurred after radiotherapy; thus, radiotherapy was associated with a significantly increased risk of developing a thoracic soft tissue sarcoma (RR 3·0 [95% CI 2·4-3·8]; p&lt;0·0001) and, for angiosarcomas, the RR for breast-conserving surgery plus radiotherapy versus mastectomy plus radiotherapy was 1·9 (1·1-3·3; p=0·012). By 10 years after radiotherapy, the cumulative incidence of thoracic soft tissue sarcoma was 0·21% (95% CI 0·12-0·34) in the KP cohort and 0·15% (95% CI 0·13-0·17) in SEER., Interpretation: Radiotherapy was the strongest risk factor for thoracic soft tissue sarcoma in both cohorts. This finding, along with the novel findings for diabetes and hypertension as potential risk factors for angiosarcomas, warrant further investigation as potential targets for prevention strategies and increased surveillance., Funding: US National Cancer Institute and National Institutes of Health., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: We evaluated differences in diagnostic mammography performance based on women's race/ethnicity., Methods: This cohort study included 267,868 diagnostic mammograms performed to evaluate screening mammogram findings at 98 facilities in the Breast Cancer Surveillance Consortium between 2005 and 2017. Mammogram assessments were recorded prospectively and breast cancers occurring within one year were ascertained. Performance statistics were calculated with 95% confidence intervals (CI) for each racial/ethnic group. Multivariable regression was used to control for personal characteristics and imaging facility., Results: Among non-Hispanic White (70%), non-Hispanic Black (13%), Asian/Pacific Islander (10%), and Hispanic (7%) women, the invasive cancer detection rate (iCDR, per 1,000 mammograms) and positive predictive value (PPV2) were highest among non-Hispanic White women (iCDR, 35.8; 95% CI, 35.0-36.7; PPV2, 27.8; 95% CI, 27.3-28.3) and lowest among Hispanic women (iCDR, 22.3; 95% CI, 20.2-24.6; PPV2, 19.4; 95% CI, 18.0-20.9). Short interval follow-up recommendations were most common among non-Hispanic Black women [(31.0%; 95% CI, 30.6%-31.5%) vs. other groups, range, 16.6%-23.6%]. False-positive biopsy recommendations were most common among Asian/Pacific Islander women [per 1,000 mammograms: 169.2; 95% CI, 164.8-173.7) vs. other groups, range, 126.5-136.1]. Some differences were explained by adjusting for receipt of diagnostic ultrasound or MRI for iCDR and imaging facility for short-interval follow-up. Other differences changed little after adjustment., Conclusions: Diagnostic mammography performance varied across racial/ethnic groups. Addressing characteristics related to imaging facility and access, rather than personal characteristics, may help reduce some of these disparities., Impact: Diagnostic mammography performance studies should include racially and ethnically diverse populations to provide an accurate view of the population-level effects., (©2022 American Association for Cancer Research.)

Background: Mammographic breast density (MBD) decline post-tamoxifen initiation is a favorable prognostic factor in estrogen receptor (ER)-positive breast cancer (BC) and has potential utility as a biomarker of tamoxifen response. However, the prognostic value of MBD decline may vary by molecular characteristics among ER-positive patients., Methods: We investigated associations between MBD decline (≥10% vs <10%) and breast cancer-specific mortality (BCSM) among ER-positive breast cancer patients aged 36-87 years at diagnosis treated with tamoxifen at Kaiser Permanente Northwest (1990-2008). Patients who died of BC (case patients; n = 62) were compared with those who did not (control patients; n = 215) overall and by tumor molecular characteristics (immunohistochemistry [IHC]-based subtype [luminal A-like: ER-positive/progesterone receptor [PR]-positive/HER2-negative/low Ki67; luminal B-like: ER-positive and 1 or more of PR-negative, HER2-positive, high Ki67] and modified IHC [mIHC]-based recurrence score of ER/PR/Ki67). Percent MBD was measured in the unaffected breast at baseline mammogram (mean = 6 months before tamoxifen initiation) and follow-up (mean = 12 months post-tamoxifen initiation). Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were computed from logistic regression models. All statistical tests were 2-sided., Results: MBD decline was statistically significantly associated with reduced risk of BCSM overall (OR = 0.38, 95% CI = 0.15 to 0.92). This association was, however, stronger among women with aggressive tumor characteristics including luminal B-like (OR = 0.17, 95% CI = 0.04 to 0.73) vs A-like (OR = 0.74, 95% CI = 0.19 to 2.92); large (OR = 0.26, 95% CI = 0.08 to 0.78) vs small (OR = 0.41, 95% CI = 0.04 to 3.79) tumors; PR-negative (OR = 0.02, 95% CI = 0.001 to 0.37) vs PR-positive (OR = 0.50, 95% CI = 0.18 to 1.40) disease; and high (OR = 0.25, 95% CI = 0.07 to 0.93) vs low (OR = 0.44, 95% CI = 0.10 to 2.09) mIHC3 score., Conclusion: The findings support MBD decline as a prognostic marker of tamoxifen response among patients with aggressive ER-positive BC phenotypes, for whom understanding treatment effectiveness is critical., (Published by Oxford University Press 2022.)

Background: It is well established that individual medications that affect the central nervous system (CNS) increase falls risk in older adults. However, less is known about risks associated with taking multiple CNS-active medications., Methods: Employing a new user design, we used data from the Adult Changes in Thought study, a prospective cohort of community-dwelling people aged 65 and older without dementia. We created a time-varying composite measure of CNS-active medication exposure from electronic pharmacy fill data and categorized into mutually exclusive categories: current (within prior 30 days), recent (31-90 days), past (91-365 days), or nonuse (no exposure in prior year). We calculated standardized daily dose and identified new initiation. Cox proportional hazards models examined the associations between exposures and the outcome of fall-related injury identified from health plan electronic databases., Results: Two thousand five hundred ninety-five people had 624 fall-related injuries over 15,531 person-years of follow-up. Relative to nonuse, fall-related injury risk was significantly greater for current use of CNS-active medication (hazard ratio [HR] = 1.95; 95% CI = 1.57-2.42), but not for recent or past use. Among current users, increased risk was noted with all doses. Risk was increased for new initiation compared with no current use (HR = 2.81; 95% CI = 2.09-3.78). Post hoc analyses revealed that risk was especially elevated with new initiation of opioids., Conclusions: We found that current use, especially new initiation, of CNS-active medications was associated with fall-related injury in community-dwelling older adults. Increased risk was noted with all dose categories. Risk was particularly increased with new initiation of opioids., (© The Author(s) 2019. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: To describe patterns of opioid use in cancer survivors., Methods: In a cohort study of colon cancer patients diagnosed during 1995-2014 and enrolled at two Kaiser Permanente regions, we constructed quarterly measures of opioid use from 1 year before cancer diagnosis through 5 years after diagnosis to examine changes in use. Measures included any use, incident use, regular use (use ≥ 45 days in a 91-day quarter), and average daily dose (converted to morphine milligram equivalent, MME). We also assessed temporal trends of opioid use., Results: Of 2,039 colon cancer patients, 11-15% received opioids in the four pre-diagnosis quarters, 68% in the first quarter after diagnosis, and 15-17% in each subsequent 19 quarters. Regular opioid use increased from 3 to 5% pre-diagnosis to 5-7% post diagnosis. Average dose increased from 15 to 17 MME/day pre-diagnosis to 14-22 MME/day post diagnosis (excluding the quarter in which cancer was diagnosed). Among post-diagnosis opioid users, 73-95% were on a low dose (< 20 MME/day). Over years, regular use of opioids increased in survivorship with no change in dosage., Conclusion: Opioid use slightly increased following a colon cancer diagnosis, but high-dose use was rare. Research is needed to differentiate under- versus over-treatment of cancer pain.

Mammographic breast density (MD) reflects breast fibroglandular content. Its decline following adjuvant tamoxifen treated, estrogen receptor (ER)-positive breast cancer has been associated with improved outcomes. Breast cancers arise from structures termed lobules, and lower MD is associated with increased age-related lobule involution. We assessed whether pre-treatment involution influenced associations between MD decline and risk of breast cancer-specific death. ER-positive tamoxifen treated patients diagnosed at Kaiser Permanente Northwest (1990-2008) were defined as cases who died of breast cancer ( n = 54) and matched controls (remained alive over similar follow-up; n = 180). Lobule involution was assessed by examining terminal duct lobular units (TDLUs) in benign tissues surrounding cancers as TDLU count/mm 2 , median span and acini count/TDLU. MD (%) was measured in the unaffected breast at baseline (median 6-months before) and follow-up (median 12-months after tamoxifen initiation). TDLU measures and baseline MD were positively associated among controls ( p < 0.05). In multivariable regression models, MD decline (≥10%) was associated with reduced risk of breast cancer-specific death before (odds ratio (OR): 0.41, 95% CI: 0.18-0.92) and after (OR: 0.41, 95% CI: 0.18-0.94) adjustment for TDLU count/mm 2 , TDLU span (OR: 0.34, 95% CI: 0.14-0.84), and acini count/TDLU (OR: 0.33, 95% CI: 0.13-0.81). MD decline following adjuvant tamoxifen is associated with reduced risk of breast cancer-specific death, irrespective of pre-treatment lobule involution.

The Wisconsin Clinical Laboratory Network (WCLN) at the University of Wisconsin-Madison is a partnership of 138 clinical and public health laboratories (as of February 2019) coordinated by the Wisconsin State Laboratory of Hygiene. This article describes the WCLN, its current activities, and lessons learned through this partnership. A laboratory technical advisory group, which consists of representatives from clinical laboratories, provides clinical laboratory perspective to the WCLN and fosters communication among laboratories. Activities and resources available through the WCLN include annual regional meetings, annual technical workshops, webinars, an email listserv, laboratory informational messages, in-person visits by a WCLN coordinator to clinical laboratories, and laboratory-based surveillance data and summaries distributed by the Wisconsin State Laboratory of Hygiene. One challenge to maintaining the WCLN is securing continual funding for network activities. Key lessons learned from this partnership of more than 20 years include the importance of in-person meetings, the clinical perspective of the laboratory technical advisory group, and providing activities and resources to clinical laboratories to foster sharing of data and clinical specimens for public health surveillance and outbreak response.

Importance: Pancreatic adenocarcinoma is the third most common cause of cancer death among men and women in the United States., Objective: To systematically review benefits and harms of screening for pancreatic adenocarcinoma to inform the US Preventive Services Task Force., Data Sources: MEDLINE, PubMed, and the Cochrane Collaboration Registry of Controlled Trials, from January 2002 through April 27, 2018; surveillance through March 22, 2019., Study Selection: Studies of adults with or without risk factors for pancreatic adenocarcinoma (eg, family history of pancreatic cancer, personal history of new-onset diabetes) undergoing imaging-based screening; studies of treatment for adults with screen-detected or asymptomatic pancreatic adenocarcinoma. Included study designs were randomized clinical trials, nonrandomized controlled intervention studies, diagnostic accuracy studies with a reference standard, cohort studies, and case-control studies (for evaluation of harms only). Studies consisting entirely of populations with known genetic syndromes associated with pancreatic cancer were excluded., Data Extraction and Synthesis: Two investigators independently reviewed abstracts and full-text articles and rated included studies for quality; data were quantitatively analyzed to calculate a pooled diagnostic yield and narratively synthesized., Main Outcomes and Measures: Mortality, morbidity, or quality of life; diagnostic accuracy of screening tests; any harm of screening or treatment., Results: Thirteen fair-quality prospective cohort screening studies (N = 1317) conducted predominantly in populations at high familial risk for pancreatic adenocarcinoma were included. No studies reported on the effect of screening on morbidity or mortality or on the effectiveness of treatment for screen-detected pancreatic adenocarcinoma. Although no studies evaluated the diagnostic accuracy of screening tests, all 13 studies reported the diagnostic yield. Yields ranged from 0 to 75 cases per 1000 persons in studies using endoscopic ultrasound, magnetic resonance imaging, and/or computed tomography-based screening. In total, 18 cases of pancreatic adenocarcinoma were detected in 1156 adults at increased familial risk and 0 cases were detected in 161 average-risk adults. In 8 studies (n = 675) assessing procedural harms of screening, no serious harms from initial screening were reported. Two studies (n = 271) found no evidence of psychosocial harms related to screening. Evidence of surgical harms was limited., Conclusions and Relevance: Imaging-based screening in groups at high familial risk can detect pancreatic adenocarcinoma with limited evidence of minimal harms. However, the effect of screening on morbidity and mortality in groups at high familial risk has not been studied, and no data are available in average-risk populations. There is limited evidence to assess benefits or harms of surgical intervention for screen-detected pancreatic adenocarcinoma.

Importance: The use of medical imaging has sharply increased over the last 2 decades. Imaging rates during pregnancy have not been quantified in a large, multisite study setting., Objective: To evaluate patterns of medical imaging during pregnancy., Design, Setting, and Participants: A retrospective cohort study was performed at 6 US integrated health care systems and in Ontario, Canada. Participants included pregnant women who gave birth to a live neonate of at least 24 weeks' gestation between January 1, 1996, and December 31, 2016, and who were enrolled in the health care system for the entire pregnancy., Exposures: Computed tomography (CT), magnetic resonance imaging, conventional radiography, angiography and fluoroscopy, and nuclear medicine., Main Outcomes and Measures: Imaging rates per pregnancy stratified by country and year of child's birth., Results: A total of 3 497 603 pregnancies in 2 211 789 women were included. Overall, 26% of pregnancies were from US sites. Most (92%) were in women aged 20 to 39 years, and 85% resulted in full-term births. Computed tomography imaging rates in the United States increased from 2.0 examinations/1000 pregnancies in 1996 to 11.4/1000 pregnancies in 2007, remained stable through 2010, and decreased to 9.3/1000 pregnancies by 2016, for an overall increase of 3.7-fold. Computed tomography rates in Ontario, Canada, increased more gradually by 2.0-fold, from 2.0/1000 pregnancies in 1996 to 6.2/1000 pregnancies in 2016, which was 33% lower than in the United States. Overall, 5.3% of pregnant women in US sites and 3.6% in Ontario underwent imaging with ionizing radiation, and 0.8% of women at US sites and 0.4% in Ontario underwent CT. Magnetic resonance imaging rates increased steadily from 1.0/1000 pregnancies in 1996 to 11.9/1000 pregnancies in 2016 in the United States and from 0.5/1000 pregnancies in 1996 to 9.8/1000 pregnancies in 2016 in Ontario, surpassing CT rates in 2013 in the United States and in 2007 in Ontario. In the United States, radiography rates doubled from 34.5/1000 pregnancies in 1996 to 72.6/1000 pregnancies in 1999 and then decreased to 47.6/1000 pregnancies in 2016; rates in Ontario slowly increased from 36.2/1000 pregnancies in 1996 to 44.7/1000 pregnancies in 2016. Angiography and fluoroscopy and nuclear medicine use rates were low (5.2/1000 pregnancies), but in most years, higher in Ontario than the United States. Imaging rates were highest for women who were younger than 20 years or aged 40 years or older, gave birth preterm, or were black, Native American, or Hispanic (US data only). Considering advanced imaging only, chest imaging of pregnant women was more likely to use CT in the United States and nuclear medicine imaging in Ontario., Conclusions and Relevance: The use of CT during pregnancy substantially increased in the United States and Ontario over the past 2 decades. Imaging rates during pregnancy should be monitored to avoid unnecessary exposure of women and fetuses to ionizing radiation.

Purpose: Hospitalizations are a common occurrence during chemotherapy for advanced cancer. Validated risk stratification tools could facilitate proactive approaches for reducing hospitalizations by identifying at-risk patients., Patients and Methods: We assembled two retrospective cohorts of patients receiving chemotherapy for advanced nonhematologic cancer; cohorts were drawn from three integrated health plans of the Cancer Research Network. We used these cohorts to develop and validate logistic regression models estimating 30-day hospitalization risk after chemotherapy initiation. The development cohort included patients in two health plans from 2005 to 2013. The validation cohort included patients in a third health plan from 2007 to 2016. Candidate predictor variables were derived from clinical data in institutional data warehouses. Models were validated based on the C-statistic, positive predictive value, and negative predictive value. Positive predictive value and negative predictive value were calculated in reference to a prespecified risk threshold (hospitalization risk ≥ 18.0%)., Results: There were 3,606 patients in the development cohort (median age, 63 years) and 634 evaluable patients in the validation cohort (median age, 64 years). Lung cancer was the most common diagnosis in both cohorts (26% and 31%, respectively). The selected risk stratification model included two variables: albumin and sodium. The model C-statistic in the validation cohort was 0.69 (95% CI, 0.62 to 0.75); 39% of patients were classified as high risk according to the prespecified threshold; 30-day hospitalization risk was 24.2% (95% CI, 19.9% to 32.0%) in the high-risk group and 8.7% (95% CI, 6.1% to 12.0%) in the low-risk group., Conclusion: A model based on data elements routinely collected during cancer treatment can reliably identify patients at high risk for hospitalization after chemotherapy initiation. Additional research is necessary to determine whether this model can be deployed to prevent chemotherapy-related hospitalizations.

Objective: Prior research examining the association between use of antidepressants after colon cancer diagnosis and risk of recurrence is scant. We evaluated this association among colon cancer patients diagnosed at two integrated health care delivery systems in the United States., Methods: We conducted a cohort study of stage I to IIIA colon cancer patients diagnosed at greater than or equal to 18 years of age at Kaiser Permanente Colorado and Kaiser Permanente Washington during 1995 to 2014. We used pharmacy records to identify dispensings for antidepressants and tumor registry records and patients' medical charts to identify cancer recurrences. Using Cox proportional hazards models, we estimated the adjusted hazard ratio (HR) of colon cancer recurrence comparing patients who used antidepressants after diagnosis to those who did not. We also evaluated the risk associated with use of selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs) separately., Results: Among the 1923 eligible colon cancer patients, 807 (42%) used an antidepressant after diagnosis and 139 had a colon cancer recurrence during an average 5.6 years of follow-up. Use of antidepressants after colon cancer diagnosis was not associated with risk of recurrence (HR: 1.14; 95% confidence interval [CI], 0.69-1.87). The HR for use of SSRIs was 1.22 (95% CI, 0.64-2.30), and for TCAs, it was 1.18 (95% CI, 0.68-2.07)., Conclusions: Our findings suggest that use of antidepressants after colon cancer diagnosis was common and not associated with risk of recurrence. Future larger studies with greater power to examine risk associated with individual antidepressants would be valuable additions to the evidence base., (© 2019 John Wiley & Sons, Ltd.)

Background: Past research has focused on risk factors for developing dementia, with increasing recognition of "resilient" people who live to old age with intact cognitive function despite pathological features of Alzheimer's disease (AD)., Objective: To evaluate demographic factors, mid-life characteristics, and non-AD neuropathology findings that may be associated with cognitive resilience to AD pathology., Methods: We analyzed data from 276 autopsy cases with intermediate or high levels of AD pathology from the Adult Changes in Thought study. We defined cognitive resilience as having Cognitive Abilities Screening Instrument scores ≥86 within two years of death and no clinical dementia diagnosis; non-resilient people had dementia diagnoses from AD or other causes before death. We compared mid-life characteristics, demographics, and additional neuropathology findings between resilient and non-resilient people. We used multivariable logistic regression to estimate odds ratios (ORs) with 95% confidence intervals (CIs) for being resilient compared to not being resilient adjusting for demographic and neuropathology factors., Results: We classified 68 (25%) people as resilient and 208 (75%) as not resilient. A greater proportion of resilient people had a college degree (50%) compared with non-resilient (32%, p = 0.01). The odds of being resilient were significantly increased among people with a college education (OR = 2.01, 95% CI = 1.01-3.99) and significantly reduced among people with additional non-AD neuropathology findings such as hippocampal sclerosis (OR = 0.28, 95% CI = 0.09-0.89) and microinfarcts (OR = 0.34, 95% CI = 0.15-0.78)., Conclusion: Increased education and absence of non-AD pathology may be independently associated with cognitive resilience, highlighting the importance of evaluating co-morbid factors in future research on mechanisms of cognitive resilience.

Objectives: To determine whether higher cumulative proton pump inhibitor (PPI) exposure is associated with greater dementia risk., Design: Prospective population-based cohort study., Setting: Kaiser Permanente Washington, an integrated healthcare delivery system in Seattle, Washington., Participants: Individuals aged 65 and older without dementia at study entry (N = 3,484)., Measurements: Participants were screened for dementia every 2 years, and those who screened positive underwent extensive evaluation. Dementia outcomes were determined using standard diagnostic criteria. Time-varying PPI exposure was determined from computerized pharmacy data and consisted of total standardized daily doses (TSDDs) dispensed to an individual in the prior 10 years. We also assessed duration of use. Multivariable Cox regression was used to estimate the association between PPI exposure and time to dementia or Alzheimer's disease (AD)., Results: Over a mean follow-up of 7.5 years, 827 participants (23.7%) developed dementia (670 with possible or probable AD). PPI exposure was not associated with risk of dementia (P = .66) or AD (P = .77). For dementia, the risk for specific levels of cumulative exposure compared to no use was: 365 TSDDs (HR 0.87, 95% CI 0.65-1.18), 1,095 TSDDs (HR 0.99, CI 0.75-1.30) and 1,825 TSDDs (HR 1.13, CI 0.82-1.56). These TSDD levels represent approximately 1, 3 and 5 years of daily use respectively. Duration of PPI use was not associated with dementia outcomes either., Conclusion: Proton pump inhibitor use was not associated with dementia risk, even for people with high cumulative exposure. Although there are other safety concerns with long-term PPI use, results from our study do not support that these medications should be avoided out of concern about dementia risk., (© 2017, Copyright the Authors Journal compilation © 2017, The American Geriatrics Society.)

The Wisconsin State Laboratory of Hygiene challenged Wisconsin laboratories to examine their biosafety practices and improve their culture of biosafety. One hundred three clinical and public health laboratories completed a questionnaire-based, microbiology-focused biosafety risk assessment. Greater than 96% of the respondents performed activities related to specimen processing, direct microscopic examination, and rapid nonmolecular testing, while approximately 60% performed culture interpretation. Although they are important to the assessment of risk, data specific to patient occupation, symptoms, and travel history were often unavailable to the laboratory and, therefore, less contributory to a microbiology-focused biosafety risk assessment than information on the specimen source and test requisition. Over 88% of the respondents complied with more than three-quarters of the mitigation control measures listed in the survey. Facility assessment revealed that subsets of laboratories that claim biosafety level 1, 2, or 3 status did not possess all of the biosafety elements considered minimally standard for their respective classifications. Many laboratories reported being able to quickly correct the minor deficiencies identified. Task assessment identified deficiencies that trended higher within the general (not microbiology-specific) laboratory for core activities, such as packaging and shipping, direct microscopic examination, and culture modalities solely involving screens for organism growth. For traditional microbiology departments, opportunities for improvement in the cultivation and management of highly infectious agents, such as acid-fast bacilli and systemic fungi, were revealed. These results derived from a survey of a large cohort of small- and large-scale laboratories suggest the necessity for continued microbiology-based understanding of biosafety practices, vigilance toward biosafety, and enforcement of biosafety practices throughout the laboratory setting., (Copyright © 2017 American Society for Microbiology.)

We compared the effectiveness of two outreach strategies on timely mammography adherence: a mammogram-specific reminder letter (sent just before a woman was due) to a birthday letter (addresses multiple preventive services and not timed around due dates). We evaluated screening mammography adherence following 79,848 mammogram-specific and 151,626 birthday letters mailed between 2002 and 2012 to women aged 40-74years enrolled in Kaiser Permanente Washington. Screening mammogram adherence was specifically tied to due date and was evaluated separately by age group and up-to-date or overdue status at the time of mailing. We used generalized estimating equations to account for correlation between repeated observations, to model the odds of screening mammography adherence by letter type. Among women up-to-date, adherence following birthday letters was 22-76% lower compared to the mammogram-specific reminders, with the greatest decreases in adherence in women aged 70-74. Birthday letters were more effective at activating screening uptake among some subgroups of overdue women aged 50-69 and most overdue women aged 70-74, but universally low adherence rates were observed in overdue women. Increasing number of recommended services for women aged 50-74 who were up-to-date resulted in 12-17% lower mammography adherence, but had no effect in women aged 40-49 or in overdue women. Birthday letters are less effective than mammogram-specific reminder letters at prompting women to undergo timely breast cancer screening, particularly among women up-to-date with screening. Birthday letters may be effective at increasing overall preventive care; however, supplemental outreach may be needed around the due date to increase timely preventive services receipt., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Introduction: Racial and ethnic disparities continue to exist in cancer screening rates, especially among US Latina and Black/African American populations. We conducted six focus groups among 41 women from these communities in order to better understand their preferences about cancer screening reminders and the motivators and deterrents they face in obtaining recommended breast, cervical, and colon cancer screening., Methods: Using self-reported patient race/ethnicity from electronic medical records of a large, integrated health care system in Seattle, we recruited women ages 30-60 to participate in one of five 2-hour focus groups. Using verbatim transcripts from these discussions, we conducted a qualitative analysis to identify common themes., Results: The focus group participants were primarily strong endorsers and utilizers of recommended breast, cervical, and colon cancer screening services. Insurance and belief in preventive care were the most common motivators that they cited in obtaining cancer screening. However, they still reported multiple barriers to getting recommended cancer screening for themselves and community members, including lack of time, conflicting information about screening intervals, distrust in the health care system, and a lack of understanding of the benefits of preventive care., Conclusions: Efforts to improve understanding about the benefits of cancer screening, clarify cancer screening guideline recommendations, increase cultural competency among health care professionals, and expand the times and locations where cancer screening is available are all options that may improve cancer screening rates among Latinas and Black/African American women.

Objective: Test-specific reminder letters can improve cancer screening adherence. Little is known about the effectiveness of a reminder system that targets the whole person by including multiple screening recommendations per letter., Methods: We compared the effectiveness of a Pap-specific reminder letter sent 27months after a woman's last Pap, to a reminder letter that included up to seven preventive service recommendations sent before a woman's birthday ("birthday letter") on Pap smear adherence from a natural experiment occurring in routine clinical care. Participants included 82,016 women from Washington State who received 72,615 Pap-specific letters between 2003 and 2007 and 100,218 birthday letters between 2009 and 2012. We defined adherence as having a Pap test within a six month window around the Pap test due date. Using logistic regression, we calculated adjusted odds ratios (OR) for adherence with 95% confidence intervals (CI) following the birthday letter with 1-2 recommendations, 3-5 recommendations, and 6-7 recommendations compared to the Pap-specific letter. All analyses were stratified by whether a woman was up-to-date or overdue for screening at the time she received a letter., Results: Adjusted ORs showed reduced adherence following the birthday letter compared with the Pap-specific letter for up-to-date women whether the letter had 1-2 recommendations (OR=0.37, 95%CI=0.36-0.39), 3-5 recommendations (OR=0.44, 95%CI=0.42-0.45), or 6-7 recommendations (OR=0.36, 95%CI=0.32-0.40). We noted no difference in Pap-test adherence between letter types for overdue women., Conclusions: In conclusion, for women regularly adherent to screening, an annual birthday letter containing reminders for multiple preventive services was less effective at promoting cervical cancer screening compared with a Pap-specific letter., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objectives: To evaluate the associations between anesthesia and dementia or Alzheimer's disease (AD) risk using prospectively collected data., Design: Cohort study., Participants: Community-dwelling members of the Adult Changes in Thought cohort aged 65 and older and free of dementia at baseline (N = 3,988)., Measurements: Participants self-reported all prior surgical procedures with general or neuraxial (spinal or epidural) anesthesia at baseline and reported new procedures every 2 years. People undergoing high-risk surgery with general anesthesia, other surgery with general anesthesia, and other surgery with neuraxial anesthesia exposures were compared with those with no surgery and no anesthesia. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for dementia and AD associated with time-varying lifetime and recent (past 5 years) anesthesia exposures., Results: At baseline, 254 (6%) people reported never having anesthesia; 248 (6%) had had one or more high-risk surgeries with general anesthesia, 3,363 (84%) had had one or more other surgeries with general anesthesia, and 123 (3%) had had one or more surgeries with neuraxial anesthesia. High-risk surgery with general anesthesia was not associated with greater risk of dementia (HR = 0.86, 95% CI = 0.58-1.28) or AD (HR = 0.95, 95% CI = 0.61-1.49) than no history of anesthesia. People with any history of other surgery with general anesthesia had a lower risk of dementia (HR = 0.63, 95% CI = 0.46-0.85) and AD (HR = 0.65, 95% CI = 0.46-0.93) than people with no history of anesthesia. There was no association between recent anesthesia exposure and dementia or AD., Conclusion: Anesthesia exposure was not associated with of dementia or AD in older adults., (© 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society.)

Background: Endocrine therapy initiation after ductal carcinoma in situ (DCIS) is highly variable and largely unexplained. National guidelines recommend considering tamoxifen for women with estrogen receptor-positive (ER+) DCIS or who undergo excision alone. We evaluated endocrine therapy use after DCIS over a 15-year period in an integrated health care setting to identify factors related to initiation., Methods: Female Group Health Cooperative enrollees ages 18-89 years with a DCIS diagnosis during 1996-2011 were eligible for inclusion. Endocrine therapy was identified through pharmacy records. Tumor and treatment information were from tumor registry reports; demographics and other risk factors were from questionnaires and electronic medical records. Relative risks (RRs) and 95% confidence intervals (CIs) for endocrine therapy initiation were calculated using multivariable generalized linear models., Results: We identified 727 women with a DCIS diagnosis, including 163 (22%) who initiated endocrine therapy (149 tamoxifen, 14 aromatase inhibitor). Younger women were more likely to initiate endocrine therapy (RR 1.69; 95% CI 1.16-2.46 for ages 45-54 vs. 65-74 years). Compared with breast-conserving surgery (BCS) with radiation, women who had BCS alone (RR 0.46; 95% CI 0.25-0.84) or mastectomy (RR 0.54; 95% CI 0.39-0.75) were less likely to use endocrine therapy. ER testing increased from 4% of DCIS cases in 2001 to 71% in 2011; however, endocrine therapy initiation decreased from 58% of ER+ DCIS in 2001-2005 to 37% in 2009-2011., Conclusion: Increasing ER testing since 2001 has not corresponded to parallel increases in endocrine therapy initiation. Age, surgery, and radiation were the primary factors associated with initiation., Implications for Practice: National guidelines recommend considering tamoxifen for women with ductal carcinoma in situ (DCIS) who are estrogen receptor-positive (ER+) or who undergo excision alone. In this study, the rapid increase in ER testing caused by tamoxifen's approval in 2000 did not lead to increases in endocrine therapy initiation, despite recognition of an increasing number of DCIS tumors as ER+ each year. Contrary to the suggested guidelines, women who had breast-conserving surgery without radiation were less likely to use tamoxifen than those who had radiation. Future Food and Drug Administration approval of new endocrine agents for DCIS (such as aromatase inhibitors) may provide an opportunity to reemphasize benefits by ER and surgery status., (©AlphaMed Press.)

Background: Antimicrobial resistance presents a threat to quality patient care. Knowledge of localantibacterial susceptibility patterns can guide clinicians in empiric antibacterial administration andassist pharmacists and infectious disease physicians in development of appropriate therapeutic pathways., Methods: To characterize Wisconsin antibacterial susceptibility patterns and elucidate geographicor temporal variation in antibacterial resistance, a retrospective, observational analysis of antibiogram data was performed. Seventy-two members of the Wisconsin Clinical Laboratory Network(WCLN) submitted antibiograms describing clinically significant isolates tested in calendar year 2013 to the WCLN Laboratory Technical Advisory Group., Results: In the context of commonly reported antibacterial agents, data were compiled for approximately 75,800 isolates of Escherichia coi; 13,300 Klebsiella pneumoniae; 6300 Proteus mirobilis;2800 Enterobacter cloacae; 8400 Pseudomonas aeruginosa; 30,000 S aureus; 11,200 coagulase-negative Staphylococcus spp; and 13,800 Enterococcus spp. P mirobilis isolates from northern Wisconsin were more likely to demonstrate resistance than those in the southern region. In contrast, P aeruginosa isolates from southern Wisconsin had decreased susceptibility to a number ofagents when compared to other regions. Temporal trending in decreased E coli and P mirabilis susceptibility to fluoroquinolones and trimethoprimsulfamethoxazole was observed. Increased methicillin-resistant Staphylococcus oureus (MRSA) rates were observed in northwest and southeastWisconsin. In general, northeast Wisconsin exhibited less frequency of antibacterial resistance., Conclusions: Geographic variation exists with respect to antibacterial resistance, particularly inareas of Wisconsin adjacent to large population centers of neighboring states. Antibacterial surveillance in Wisconsin is indicated on a regular basis to assess emerging trends in antibacterial resistance. Existing WCLN infrastructure allows for such investigations.

Tamoxifen-associated mammographic density (MD) reductions are linked to improved breast cancer survival. We evaluated MD at six time points to determine the timing of greatest reduction following tamoxifen initiation. We sampled 40 Kaiser Permanente Northwest estrogen receptor (ER)-positive breast cancer patients from a prior study of MD change, according to tamoxifen use duration and age at diagnosis: <4 years tamoxifen and ≤50 years (N = 6) or >50 years (N = 10) old; ≥4 years tamoxifen and ≤50 years (N = 13) or >50 years (N = 11) old. A single reader evaluated percent MD in the contralateral breast on baseline (pre-diagnosis) and five approximately yearly post-diagnostic (T1 to T5) mammograms. Mean MD change was calculated. Interactions with age (≤50 and >50 years), tamoxifen duration (<4 and ≥4 years), and baseline MD (tertiles) were tested in linear regression models. Overall, the largest MD decline occurred by T1 (mean 4.5%) with little additional decline by T5. Declines differed by tertile of baseline MD (Pinteraction < 0.01). In the highest tertile, the largest reduction occurred by T1 (mean 14.9%), with an additional reduction of 3.6% by T5. Changes were smaller in the middle and lowest baseline MD tertiles, with cumulative reductions of 3.0% and 0.4% from baseline to T5, respectively. There were no differences by age (Pinteraction = 0.36) or tamoxifen duration (Pinteraction = 0.42). Among ER-positive patients treated with tamoxifen and surviving ≥5 years, most of the MD reduction occurred within approximately 12 months of tamoxifen initiation, suggesting that MD measurement at a single time point following tamoxifen initiation can identify patients with substantial density declines., (©2015 American Association for Cancer Research.)

Purpose: Women with breast cancer frequently use antidepressants; however, questions about the effect of these medications on breast cancer recurrence remain., Methods: We identified 4,216 women ≥18 years with an incident stage I or II breast cancer diagnosed between 1990 and 2008 in a mixed-model healthcare delivery system linked to a cancer registry. Recurrences were ascertained from chart review. Medication exposures were extracted from electronic pharmacy records. We used multivariable Cox proportional hazards models to estimate hazard ratios (HR) and 95 % confidence intervals (CI) to assess the association between antidepressant use and breast cancer recurrence and mortality. We also conducted analyses restricted to tamoxifen users., Results: Antidepressants overall, tricyclic antidepressants, and selective serotonin reuptake inhibitors were not associated with risk of breast cancer recurrence or mortality. Women taking paroxetine only (adjusted HR: 1.66; 95 % CI 1.02, 2.71) and trazodone only (adjusted HR: 1.76; 95 % CI 1.06, 2.92), but not fluoxetine only (adjusted HR: 0.92; 95 % CI 0.55, 1.53), had higher recurrence risks than antidepressant nonusers. There was some suggestion of an increased recurrence risk with concurrent paroxetine and tamoxifen use compared with users of tamoxifen only (adjusted HR: 1.49; 95 % CI 0.79, 2.83)., Conclusions: In general, antidepressants did not appear increase risk of breast cancer recurrence, though there were some suggested increases in risk that warrant further investigation in other datasets. Our results combined systematically and quantitatively with results from other studies may be useful for patients and providers making decisions about antidepressant use after breast cancer diagnosis.

Purpose: Little is known regarding toxicities and hospitalizations in community-based settings for patients with advanced non-small-cell lung cancer (NSCLC) who received commonly prescribed carboplatin-paclitaxel (CP) or carboplatin-paclitaxel-bevacizumab (CPB) chemotherapy., Methods: Patients with stages IIIB-IV NSCLC age ≥ 21 years diagnosed between 2005 and 2010 who received first-line CP or CPB were identified at four health maintenance organizations (N = 1,109). Using patient and tumor characteristics and hospital and ambulatory encounters from automated data in the 180 days after chemotherapy initiation, the association between CP and CPB and toxicities and hospitalizations were evaluated with χ(2) tests and propensity score-adjusted regression models., Results: Patients who received CPB were significantly younger and had significantly more bleeding, proteinuria, and GI perforation events (all P < .05). For these patients, the unadjusted odds ratio associated with the likelihood of having a hospitalization was 0.46 (95% CI, 0.32 to 0.67). As shown by multivariable and propensity score-adjusted models, patients who received CPB were less likely to have been hospitalized (odds ratio, 0.48; 95% CI, 0.32 to 0.71) and had fewer total hospitalizations (rate ratio, 0.62; 95% CI, 0.47 to 0.82) and hospital days (rate ratio, 0.53; 95% CI, 0.47 to 0.60) than patients who received CP., Conclusion: Consistent with earlier randomized clinical trials, significantly more toxicity events were identified in patients treated with CPB. However, both unadjusted and adjusted models showed that patients who received CPB were less likely than patients who received CP to experience a hospital-related event after the initiation of chemotherapy. Findings here confirm the need for adherence to clinical recommendations for judicious use of CPB, but provide reassurance regarding the relative risk for hospitalizations., (Copyright © 2015 by American Society of Clinical Oncology.)

USA states have begun legislating mammographic breast density reporting to women, requiring that women undergoing screening mammography who have dense breast tissue (Breast Imaging Reporting and Data System [BI-RADS] density c or d) receive written notification of their breast density; however, the impact that misclassification of breast density will have on this reporting remains unclear. The aim of this study was to assess reproducibility of the four-category BI-RADS density measure and examine its relationship with a continuous measure of percent density. We enrolled 19 radiologists, experienced in breast imaging, from a single integrated health care system. Radiologists interpreted 341 screening mammograms at two points in time 6 months apart. We assessed intra- and interobserver agreement in radiologists'; interpretations of BI-RADS density and explored whether agreement depended upon radiologist characteristics. We examined the relationship between BI-RADS density and percent density in a subset of 282 examinations. Intraradiologist agreement was moderate to substantial, with kappa varying across radiologists from 0.50 to 0.81 (mean = 0.69, 95% CI [0.63, 0.73]). Intraradiologist agreement was higher for radiologists with ≥10 years experience interpreting mammograms (difference in mean kappa = 0.10, 95% CI [0.01, 0.24]). Interradiologist agreement varied widely across radiologist pairs from slight to substantial, with kappa ranging from 0.02 to 0.72 (mean = 0.46, 95% CI [0.36, 0.55]). Of 145 examinations interpreted as "nondense" (BI-RADS density a or b) by the majority of radiologists, 82.8% were interpreted as "dense" (BI-RADS density c or d) by at least one radiologist. Of 187 examinations interpreted as "dense" by the majority of radiologists, 47.1% were interpreted as "nondense" by at least one radiologist. While the examinations of almost half of the women in our study were interpreted clinically as having BI-RADS density c or d, only about 10% of examinations had percent density >50%. Our results suggest that breast density reporting based on a single BI-RADS density interpretation may be misleading due to high interradiologist variability and a lack of correspondence between BI-RADS density and percent density., (© 2015 Wiley Periodicals, Inc.)

Background: Pathology reports typically require manual review to abstract research data. We developed a natural language processing (NLP) system to automatically interpret free-text breast pathology reports with limited assistance from manual abstraction., Methods: We used an iterative approach of machine learning algorithms and constructed groups of related findings to identify breast-related procedures and results from free-text pathology reports. We evaluated the NLP system using an all-or-nothing approach to determine which reports could be processed entirely using NLP and which reports needed manual review beyond NLP. We divided 3234 reports for development (2910, 90%), and evaluation (324, 10%) purposes using manually reviewed pathology data as our gold standard., Results: NLP correctly coded 12.7% of the evaluation set, flagged 49.1% of reports for manual review, incorrectly coded 30.8%, and correctly omitted 7.4% from the evaluation set due to irrelevancy (i.e. not breast-related). Common procedures and results were identified correctly (e.g. invasive ductal with 95.5% precision and 94.0% sensitivity), but entire reports were flagged for manual review because of rare findings and substantial variation in pathology report text., Conclusions: The NLP system we developed did not perform sufficiently for abstracting entire breast pathology reports. The all-or-nothing approach resulted in too broad of a scope of work and limited our flexibility to identify breast pathology procedures and results. Our NLP system was also limited by the lack of the gold standard data on rare findings and wide variation in pathology text. Focusing on individual, common elements and improving pathology text report standardization may improve performance.