Postpartum Breast Cancer and Survival in Women With Germline BRCA Pathogenic Variants.

Importance: In young-onset breast cancer (YOBC), a diagnosis within 5 to 10 years of childbirth is associated with increased mortality. Women with germline BRCA1/2 pathogenic variants (PVs) are more likely to be diagnosed with BC at younger ages, but the impact of childbirth on mortality is unknown. Objective: To determine whether time between most recent childbirth and BC diagnosis is associated with mortality among patients with YOBC and germline BRCA1/2 PVs. Design, Setting, and Participants: This prospective cohort study included women with germline BRCA1/2 PVs diagnosed with stage I to III BC at age 45 years or younger between 1950 and 2021 in the United Kingdom, who were followed up until November 2021. Data were analyzed from December 3, 2021, to November 29, 2023. Exposure: Time between most recent childbirth and subsequent BC diagnosis, with recent childbirth defined as 0 to less than 10 years, further delineated to 0 to less than 5 years and 5 to less than 10 years. Main Outcomes and Measures: The primary outcome was all-cause mortality, censored at 20 years after YOBC diagnosis. Mortality of nulliparous women was compared with the recent post partum groups and the 10 or more years post partum group. Cox proportional hazards regression analyses were adjusted for age, tumor stage, and further stratified by tumor estrogen receptor (ER) and BRCA gene status. Results: Among 903 women with BRCA PVs (mean [SD] age at diagnosis, 34.7 [6.1] years; mean [SD] follow-up, 10.8 [9.8] years), 419 received a BC diagnosis 0 to less than 10 years after childbirth, including 228 women diagnosed less than 5 years after childbirth and 191 women diagnosed 5 to less than 10 years after childbirth. Increased all-cause mortality was observed in women diagnosed within 5 to less than 10 years post partum (hazard ratio [HR], 1.56 [95% CI, 1.05-2.30]) compared with nulliparous women and women diagnosed 10 or more years after childbirth, suggesting a transient duration of postpartum risk. Risk of mortality was greater for women with ER-positive BC in the less than 5 years post partum group (HR, 2.35 [95% CI, 1.02-5.42]) and ER-negative BC in the 5 to less than 10 years post partum group (HR, 3.12 [95% CI, 1.22-7.97]) compared with the nulliparous group. Delineated by BRCA1 or BRCA2, mortality in the 5 to less than 10 years post partum group was significantly increased, but only for BRCA1 carriers (HR, 2.03 [95% CI, 1.15-3.58]). Conclusions and Relevance: These findings suggest that YOBC with germline BRCA PVs was associated with increased risk for all-cause mortality if diagnosed within 10 years after last childbirth, with risk highest for ER-positive BC diagnosed less than 5 years post partum, and for ER-negative BC diagnosed 5 to less than 10 years post partum. BRCA1 carriers were at highest risk for poor prognosis when diagnosed at 5 to less than 10 years post partum. No such associations were observed for BRCA2 carriers. These results should inform genetic counseling, prevention, and treatment strategies for BRCA PV carriers.

Screening for Chlamydial and Gonococcal Infections: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: The 2014 US Preventive Services Task Force (USPSTF) recommendation statement supported the effectiveness of screening for chlamydia and gonorrhea in asymptomatic, sexually active women 24 years or younger and in older women at increased risk for infection, although evidence for screening in men was insufficient. Objective: To update the 2014 USPSTF review on screening for chlamydial and gonococcal infection in adults and adolescents, including those who are pregnant. Data Sources: Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Ovid MEDLINE (January 1, 2014, through May 28, 2020) with surveillance through May 21, 2021. Study Selection: Randomized clinical trials and observational studies of screening effectiveness, accuracy of risk stratification and alternative screening methods, accuracy of tests, and screening harms. Data Extraction and Synthesis: One investigator abstracted data; a second checked accuracy. Two investigators independently assessed study quality. Main Outcomes and Measures: Complications of infection; infection transmission or acquisition; diagnostic accuracy of anatomical site-specific testing and collection methods; screening harms. Results: Twenty-seven studies were included (N = 179 515). Chlamydia screening compared with no screening was significantly associated with reduced risk of pelvic inflammatory disease (PID) in 2 of 4 trials and with reduced hospital-diagnosed PID (0.24% vs 0.38%); relative risk, 0.6 [95% CI, 0.4-1.0]), but not clinic-diagnosed PID or epididymitis, in the largest trial. In studies of risk prediction instruments in asymptomatic women, age younger than 22 years demonstrated comparable accuracy to extensive criteria. Sensitivity of chlamydial testing was similar at endocervical (89%-100%) and self- and clinician-collected vaginal (90%-100%) sites for women and at meatal (100%), urethral (99%), and rectal (92%) sites for men but lower at pharyngeal sites (69.2%) for men who have sex with men. Sensitivity of gonococcal testing was 89% or greater for all anatomical samples. False-positive and false-negative testing rates were low across anatomical sites and collection methods. Conclusions and Relevance: Screening for chlamydial infection was significantly associated with a lower risk of PID in young women. Risk prediction criteria demonstrated limited accuracy beyond age. Testing for asymptomatic chlamydial and gonococcal infections was highly accurate at most anatomical sites, including urine and self-collected specimens. Effectiveness of screening in men and during pregnancy, optimal screening intervals, and adverse effects of screening require further evaluation.

Association of Second-Opinion Strategies in the Histopathologic Diagnosis of Cutaneous Melanocytic Lesions With Diagnostic Accuracy and Population-Level Costs.

IMPORTANCE: Diagnostic variation among pathologists interpreting cutaneous melanocytic lesions could lead to suboptimal care. OBJECTIVE: To estimate the potential association of second-opinion strategies in the histopathologic diagnosis of cutaneous melanocytic lesions with diagnostic accuracy and 1-year population-level costs in the US. DESIGN, SETTING, AND PARTICIPANTS: Decision analysis with 1-year time horizon including melanocytic lesion diagnoses available from US pathologists participating in the Melanoma Pathology Study (M-Path) and from the study panel of reference pathologists who classified cases using the MPATH-Dx classification tool. M-Path data collection occurred from July 2013 through March 2015; analyses for the present study were performed between April 2015 and January 2021. EXPOSURES: Various second-opinion strategies for interpretation of melanocytic cutaneous lesions. MAIN OUTCOMES AND MEASURES: Estimated accuracy of pathologists' diagnoses, defined as concordance with the reference panel diagnoses, and 1-year postbiopsy medical costs under various second-opinion strategies. Expected percentage of concordant diagnoses, including percentages of overinterpretation and underinterpretation, and 1-year costs of medical care per 100 000 in the US population. RESULTS: Decision-analytic model parameters were based on diagnostic interpretations for 240 cases by 187 pathologists compared with reference panel diagnoses. Without second opinions, 83.2% of diagnoses in the US were estimated to be accurate-ie, concordant with the reference diagnosis; with overinterpretation (8.0%) or underinterpretation (8.8%), and 16 850 misclassified diagnoses per 100 000 biopsies. Accuracy increased under all second-opinion strategies. Accuracy (87.4% concordance with 3.6% overinterpretation and 9.1% underinterpretation) and cost (an increase of more than $10 million per 100 000 biopsies per year) were highest when second opinions were universal (eg, performed on all biopsies), relative to no second opinions. A selective second-opinion strategy based on pathologists' desire or institutional requirements for a second opinion was most accurate (86.5% concordance; 4.4% overinterpretation; 9.1% underinterpretation) and would reduce costs by more than $1.9 million per 100 000 skin biopsies relative to no second opinions. Improvements in diagnostic accuracy with all second-opinion strategies were associated with reductions in overinterpretation but not underinterpretation. CONCLUSIONS AND RELEVANCE: In this decision-analytic model, selective second-opinion strategies for interpretation of melanocytic skin lesions showed the potential to improve diagnostic accuracy and decrease costs relative to no second opinions or universal second opinions.

Effectiveness of Patient Navigation to Increase Cancer Screening in Populations Adversely Affected by Health Disparities: a Meta-analysis.

BACKGROUND: This study evaluates the effectiveness of patient navigation to increase screening for colorectal, breast, and cervical cancer in populations adversely affected by health care disparities. METHODS: Eligible studies were identified through English-language searches of Ovid® MEDLINE®, PsycINFO®, SocINDEX, and Veterans Affairs Health Services database (January 1, 1996, to July 5, 2019) and manual review of reference lists. Randomized trials and observational studies of relevant populations that evaluated the effectiveness of patient navigation on screening rates for colorectal, breast, or cervical cancer compared with usual or alternative care comparison groups were included. Two investigators independently abstracted study data and assessed study quality and applicability using criteria adapted from the U.S. Preventive Services Task Force. Discrepancies were resolved by consensus with a third reviewer. Results were combined using profile likelihood random effects models. RESULTS: Thirty-seven studies met inclusion criteria (28 colorectal, 11 breast, 4 cervical cancers including 3 trials with multiple cancer types). Screening rates were higher with patient navigation for colorectal cancer overall (risk ratio [RR] 1.64; 95% confidence interval [CI] 1.42 to 1.92; I2 = 93.7%; 22 trials) and by type of test (fecal occult blood or immunohistochemistry testing [RR 1.69; 95% CI 1.33 to 2.15; I2 = 80.5%; 6 trials]; colonoscopy/endoscopy [RR 2.08; 95% CI 1.08 to 4.56; I2 = 94.6%; 6 trials]). Screening was also higher with navigation for breast cancer (RR 1.50; 95% CI 1.22 to 1.91; I2 = 98.6%; 10 trials) and cervical cancer (RR 1.11; 95% CI 1.05 to 1.19; based on the largest trial). The high heterogeneity of cervical cancer studies prohibited meta-analysis. Results were similar for colorectal and breast cancer regardless of prior adherence to screening guidelines, follow-up time, and study quality. CONCLUSIONS: In populations adversely affected by disparities, colorectal, breast, and cervical cancer screening rates were higher in patients provided navigation services. Registration: PROSPERO: CRD42018109263.

Screening for Anxiety in Adolescent and Adult Women: A Systematic Review for the Women's Preventive Services Initiative.

BACKGROUND: Anxiety disorders are infrequently recognized during routine health care even though they are common in adolescent girls and adult women. PURPOSE: To evaluate evidence on the effectiveness of screening for anxiety disorders in primary care in improving symptoms, function, and quality of life; harms of screening; accuracy of screening instruments; and effectiveness and harms of treatments. DATA SOURCES: English-language searches of Ovid MEDLINE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Health and Psychosocial Instruments (1 January 1996 to 4 November 2019); ClinicalTrials.gov (November 2019); and reference lists of studies and reviews. STUDY SELECTION: Studies that enrolled adolescent girls and adult women not currently diagnosed with anxiety disorders, including pregnant or postpartum women, and compared clinical outcomes and harms between women who were and were not screened; diagnostic accuracy studies of screening instruments; and systematic reviews of randomized trials of behavioral and pharmacologic treatments. DATA EXTRACTION: Dual extraction and quality assessment of individual studies. DATA SYNTHESIS: No studies evaluated the overall effectiveness or harms of screening. Thirty-three studies and 2 systematic reviews (171 studies; 112 574 participants) evaluated the diagnostic accuracy of 27 screening instruments and their variations against a clinical diagnosis or other instruments. Most demonstrated moderate to high accuracy for adults (Generalized Anxiety Disorder scale: sensitivity, 70% to 97%; specificity, 50% to 89%), pregnant and postpartum women (Edinburgh Postnatal Depression Scale: sensitivity, 74%; specificity, 64%), and adolescents (Screen for Child Anxiety Related Emotional Disorders: sensitivity, 64% to 74%; specificity, 64% to 73%). Anxiety symptoms improved with cognitive behavioral therapy (246 randomized controlled trials; 17 209 participants) and antianxiety medications (126 randomized controlled trials; 8225 participants). LIMITATION: Limited data on long-term harms of treatment and no treatment trials in pregnant or postpartum women. CONCLUSION: Evidence on the overall effectiveness and harms of screening for anxiety is insufficient. Most screening instruments are moderately to highly accurate. Behavioral therapies and antianxiety medications effectively improve anxiety symptoms. PRIMARY FUNDING SOURCE: Health Resources and Services Administration.

Screening for Anxiety in Adolescent and Adult Women: A Recommendation From the Women's Preventive Services Initiative.

DESCRIPTION: The Women's Preventive Services Initiative (WPSI), a national coalition of women's health professional organizations and patient representatives, developed a recommendation on screening for anxiety in adolescent and adult women to improve detection; achieve earlier diagnosis and treatment; and improve health, function, and well-being. The WPSI's recommendations are intended to guide clinical practice and coverage of services for the Health Resources and Services Administration and other stakeholders. The target audience for this recommendation includes all clinicians providing preventive health care to women, particularly in primary care settings. This recommendation applies to women and adolescent girls aged 13 years or older who are not currently diagnosed with anxiety disorders, including pregnant and postpartum women. METHODS: The WPSI developed this recommendation after evaluating results of a systematic review of the effectiveness of screening, accuracy of screening instruments, and benefits and harms of treatments in adolescent girls and adult women. No studies directly evaluated the overall effectiveness or harms of screening for anxiety. Twenty-seven screening instruments and their variations were moderately to highly accurate in identifying anxiety (33 individual studies and 2 systematic reviews; 171 studies total). Symptoms improved and relapse rates decreased with psychological therapies (246 randomized controlled trials [RCTs] in 5 systematic reviews) and with selective serotonin reuptake inhibitors or selective serotonin and norepinephrine reuptake inhibitors (126 RCTs in 3 systematic reviews). The WPSI also considered the effect of screening on symptom progression and identification of associated and underlying conditions, as well as implementation factors. RECOMMENDATION: The WPSI recommends screening for anxiety in women and adolescent girls aged 13 years or older who are not currently diagnosed with anxiety disorders, including pregnant and postpartum women. Optimal screening intervals are unknown, and clinical judgment should be used to determine frequency. When screening suggests the presence of anxiety, further evaluation is necessary to establish the diagnosis and determine appropriate treatment and follow-up.

Use of an Online Breast Cancer Risk Assessment and Patient Decision Aid in Primary Care Practices.

Background: U.S. Preventive Services Task Force (USPSTF) recommendations for mammography screening, genetic counseling and testing for pathogenic BRCA1/2 mutations, and use of risk-reducing medications require assessment of breast cancer risk for clinical decision-making, but efficient methods for risk assessment in clinical practice are lacking. Materials and Methods: A cross-sectional study evaluating a web-based breast cancer risk assessment and decision aid (MammoScreen) was conducted in an academic general internal medicine clinic. All eligible women, 40-74 years of age without previous diagnosis of breast or ovarian cancer and who were enrolled in the Epic MyChart patient portal were invited. MammoScreen uptake and completion rates and consistency between breast cancer risk determined by MammoScreen and existing risk information in the Epic record were measured. Patient and physician experiences were summarized from interviews. Results: Of 448 invited participants, 339 (75.7%) read their MyChart invitation and 125 (36.9%) who read invitations enrolled in the study; 118 (94.4% of enrolled) completed MammoScreen. Twenty-one women were categorized as above-average risk from either MammoScreen data or the chart review and 7 (33.3%) were identified by both sources. Physicians and patients believed MammoScreen was easy to use and was helpful in identifying risks and facilitating shared decision-making. Conclusions: Breast cancer risk assessment and mammography screening decision support were efficiently implemented through a web-based tool for patients sent through an electronic patient portal. Integration of patient decision aids with risk algorithms in clinical practice may help support the implementation of USPSTF recommendations that include risk assessment and shared decision-making.

Achieving Health Equity in Preventive Services: A Systematic Review for a National Institutes of Health Pathways to Prevention Workshop.

Background: Disadvantaged populations in the United States experience disparities in the use of preventive health services. Purpose: To examine effects of barriers that create health disparities in 10 recommended preventive services for adults, and to evaluate the effectiveness of interventions to reduce them. Data Sources: English-language searches of Ovid MEDLINE, PsycINFO, SocINDEX, and the Veterans Affairs Health Services database (1 January 1996 to 5 July 2019); reference lists. Study Selection: Trials, observational studies with comparison groups, and systematic reviews of populations adversely affected by disparities that reported effects of barriers on use of any of the 10 selected preventive services or that reported the effectiveness of interventions to reduce disparities in use of a preventive service by improving intermediate or clinical outcomes. Data Extraction: Dual extraction and assessment of study quality, strength of evidence, and evidence applicability. Data Synthesis: No studies reported effects of provider-specific barriers on preventive service use. Eighteen studies reporting effects of patient barriers, such as insurance coverage or lack of a regular provider, on preventive service use had mixed and inconclusive findings. Studies of patient-provider interventions (n = 12), health information technologies (n = 11), and health system interventions (n = 88) indicated higher cancer screening rates with patient navigation; telephone calls, prompts, and other outreach methods; reminders involving lay health workers; patient education; risk assessment, counseling, and decision aids; screening checklists; community engagement; and provider training. Single studies showed that clinician-delivered and technology-assisted interventions improved rates of smoking cessation and weight loss, respectively. Limitation: Insufficient or low strength of evidence and applicability for most interventions except patient navigation, telephone calls and prompts, and reminders involving lay health workers. Conclusion: In populations adversely affected by disparities, patient navigation, telephone calls and prompts, and reminders involving lay health workers increase cancer screening. Primary Funding Source: National Institutes of Health Office of Disease Prevention through an interagency agreement with the Agency for Healthcare Research and Quality. (PROSPERO: CRD42018109263).

Assessment of Second-Opinion Strategies for Diagnoses of Cutaneous Melanocytic Lesions.

Importance: Histopathologic criteria have limited diagnostic reliability for a range of cutaneous melanocytic lesions. Objective: To evaluate the association of second-opinion strategies by general pathologists and dermatopathologists with the overall reliability of diagnosis of difficult melanocytic lesions. Design, Setting, and Participants: This diagnostic study used samples from the Melanoma Pathology Study, which comprises 240 melanocytic lesion samples selected from a dermatopathology laboratory in Bellevue, Washington, and represents the full spectrum of lesions from common nevi to invasive melanoma. Five sets of 48 samples were evaluated independently by 187 US pathologists from July 15, 2013, through May 23, 2016. Data analysis was performed from April 2016 through November 2017. Main Outcomes and Measures: Accuracy of diagnosis, defined as concordance with an expert consensus diagnosis of 3 experienced pathologists, was assessed after applying 10 different second-opinion strategies. Results: Among the 187 US pathologists examining the 24 lesion samples, 113 were general pathologists (65 men [57.5%]; mean age at survey, 53.7 years [range, 33.0-79.0 years]) and 74 were dermatopathologists (49 men [66.2%]; mean age at survey, 46.4 years [range, 33.0-77.0 years]). Among the 8976 initial case interpretations, physicians desired second opinions for 3899 (43.4%), most often for interpretation of severely dysplastic nevi. The overall misclassification rate was highest when interpretations did not include second opinions and initial reviewers were all general pathologists lacking subspecialty training (52.8%; 95% CI, 51.3%-54.3%). When considering different second opinion strategies, the misclassification of melanocytic lesions was lowest when the first, second, and third consulting reviewers were subspecialty-trained dermatopathologists and when all lesions were subject to second opinions (36.7%; 95% CI, 33.1%-40.7%). When the second opinion strategies were compared with single interpretations without second opinions, the reductions in misclassification rates for some of the strategies were statistically significant, but none of the strategies eliminated diagnostic misclassification. Melanocytic lesions in the middle of the diagnostic spectrum had the highest misclassification rates (eg, moderately or severely dysplastic nevus, Spitz nevus, melanoma in situ, and pathologic stage [p]T1a invasive melanoma). Variability of in situ and thin invasive melanoma was relatively intractable to all examined strategies. Conclusions and Relevance: The results of this study suggest that second opinions rendered by dermatopathologists improve reliability of melanocytic lesion diagnosis. However, discordance among pathologists remained high.

Medication Use for the Risk Reduction of Primary Breast Cancer in Women: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Medications to reduce risk of breast cancer are effective for women at increased risk but also cause adverse effects. Objective: To update the 2013 US Preventive Services Task Force systematic review on medications to reduce risk of primary (first diagnosis) invasive breast cancer in women. Data Sources: Cochrane Central Register of Controlled Trials and Database of Systematic Reviews, EMBASE, and MEDLINE (January 1, 2013, to February 1, 2019); manual review of reference lists. Study Selection: Discriminatory accuracy studies of breast cancer risk assessment methods; randomized clinical trials of tamoxifen, raloxifene, and aromatase inhibitors for primary breast cancer prevention; studies of medication adverse effects. Data Extraction and Synthesis: Investigators abstracted data on methods, participant characteristics, eligibility criteria, outcome ascertainment, and follow-up. Results of individual trials were combined by using a profile likelihood random-effects model. Main Outcomes and Measures: Probability of breast cancer in individuals (area under the receiver operating characteristic curve [AUC]); incidence of breast cancer, fractures, thromboembolic events, coronary heart disease events, stroke, endometrial cancer, and cataracts; and mortality. Results: A total of 46 studies (82 articles [>5 million participants]) were included. Eighteen risk assessment methods in 25 studies reported low accuracy in predicting the probability of breast cancer in individuals (AUC, 0.55-0.65). In placebo-controlled trials, tamoxifen (risk ratio [RR], 0.69 [95% CI, 0.59-0.84]; 4 trials [n = 28 421]), raloxifene (RR, 0.44 [95% CI, 0.24-0.80]; 2 trials [n = 17 806]), and the aromatase inhibitors exemestane and anastrozole (RR, 0.45 [95% CI, 0.26-0.70]; 2 trials [n = 8424]) were associated with a lower incidence of invasive breast cancer. Risk for invasive breast cancer was higher for raloxifene than tamoxifen in 1 trial after long-term follow-up (RR, 1.24 [95% CI, 1.05-1.47]; n = 19 747). Raloxifene was associated with lower risk for vertebral fractures (RR, 0.61 [95% CI, 0.53-0.73]; 2 trials [n = 16 929]) and tamoxifen was associated with lower risk for nonvertebral fractures (RR, 0.66 [95% CI, 0.45-0.98]; 1 trial [n = 13 388]) compared with placebo. Tamoxifen and raloxifene were associated with increased thromboembolic events compared with placebo; tamoxifen was associated with more events than raloxifene. Tamoxifen was associated with higher risk of endometrial cancer and cataracts compared with placebo. Symptomatic effects (eg, vasomotor, musculoskeletal) varied by medication. Conclusions and Relevance: Tamoxifen, raloxifene, and aromatase inhibitors were associated with lower risk of primary invasive breast cancer in women but also were associated with adverse effects that differed between medications. Risk stratification methods to identify patients with increased breast cancer risk demonstrated low accuracy.

Risk Assessment, Genetic Counseling, and Genetic Testing for BRCA-Related Cancer in Women: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Pathogenic mutations in breast cancer susceptibility genes BRCA1 and BRCA2 increase risks for breast, ovarian, fallopian tube, and peritoneal cancer in women; interventions reduce risk in mutation carriers. Objective: To update the 2013 US Preventive Services Task Force review on benefits and harms of risk assessment, genetic counseling, and genetic testing for BRCA1/2-related cancer in women. Data Sources: Cochrane libraries; MEDLINE, PsycINFO, EMBASE (January 1, 2013, to March 6, 2019, for updates; January 1, 1994, to March 6, 2019, for new key questions and populations); reference lists. Study Selection: Discriminatory accuracy studies, randomized clinical trials (RCTs), and observational studies of women without recently diagnosed BRCA1/2-related cancer. Data Extraction and Synthesis: Data on study methods, setting, population characteristics, eligibility criteria, interventions, numbers enrolled and lost to follow-up, outcome ascertainment, and results were abstracted. Two reviewers independently assessed study quality. Main Outcomes and Measures: Cancer incidence and mortality; discriminatory accuracy of risk assessment tools for BRCA1/2 mutations; benefits and harms of risk assessment, genetic counseling, genetic testing, and risk-reducing interventions. Results: For this review, 103 studies (110 articles; N = 92 712) were included. No studies evaluated the effectiveness of risk assessment, genetic counseling, and genetic testing in reducing incidence and mortality of BRCA1/2-related cancer. Fourteen studies (n = 43 813) of 8 risk assessment tools to guide referrals to genetic counseling demonstrated moderate to high accuracy (area under the receiver operating characteristic curve, 0.68-0.96). Twenty-eight studies (n = 8060) indicated that genetic counseling was associated with reduced breast cancer worry, anxiety, and depression; increased understanding of risk; and decreased intention for testing. Twenty studies (n = 4322) showed that breast cancer worry and anxiety were higher after testing for women with positive results and lower for others; understanding of risk was higher after testing. In 8 RCTs (n = 54 651), tamoxifen (relative risk [RR], 0.69 [95% CI, 0.59-0.84]; 4 trials), raloxifene (RR, 0.44 [95% CI, 0.24-0.80]; 2 trials), and aromatase inhibitors (RR, 0.45 [95% CI, 0.26-0.70]; 2 trials) were associated with lower risks of invasive breast cancer compared with placebo; results were not specific to mutation carriers. Mastectomy was associated with 90% to 100% reduction in breast cancer incidence (6 studies; n = 2546) and 81% to 100% reduction in breast cancer mortality (1 study; n = 639); oophorectomy was associated with 69% to 100% reduction in ovarian cancer (2 studies; n = 2108); complications were common with mastectomy. Conclusions and Relevance: Among women without recently diagnosed BRCA1/2-related cancer, the benefits and harms of risk assessment, genetic counseling, and genetic testing to reduce cancer incidence and mortality have not been directly evaluated by current research.

Concordance and Reproducibility of Melanoma Staging According to the 7th vs 8th Edition of the AJCC Cancer Staging Manual.

IMPORTANCE: The recently updated American Joint Committee on Cancer (AJCC) classification of cancer staging, the AJCC Cancer Staging Manual, 8th edition (AJCC 8), includes revisions to definitions of T1a vs T1b or greater. The Melanoma Pathology Study database affords a comparison,of pathologists' concordance and reproducibility in the microstaging of melanoma according to both the existing 7th edition (AJCC 7) and the new AJCC 8. OBJECTIVE: To compare AJCC 7 and AJCC 8 to examine whether changes to the definitions of T1a and T1b or greater are associated with changes in concordance and reproducibility. DESIGN SETTING AND PARTICIPANTS: In this diagnostic study conducted as part of the national Melanoma Pathology Study across US states, 187 pathologists interpreting melanocytic skin lesions in practice completed 4342 independent case interpretations of 116 invasive melanoma cases. A consensus reference diagnosis and participating pathologists' interpretations were classified into the Melanocytic Pathology Assessment Tool and Hierarchy for Diagnosis class IV (T1a) or class V ( T1b) using both the AJCC 7 and AJCC 8 criteria. MAIN OUTCOMES AND MEASURES: Concordance with consensus reference diagnosis, interobserver reproducibility, and intraobserver reproducibility. RESULTS: For T1a diagnoses, participating pathologists' concordance with the consensus reference diagnosis increased from 44% (95% CI, 41%-48%) to 54% (95% CI, 51%-57%) using AJCC 7 and AJCC 8 criteria, respectively. The concordance for cases of T1b or greater increased from 72% (95% CI, 69%-75%) to 78% (95% CI, 75%-80%). Intraobserver reproducibility of diagnoses also improved, increasing from 59% (95% CI, 56%-63%) to 64% (95% CI, 62%-67%) for T1a invasive melanoma, and from 74% (95% CI, 71%-76%) to 77% (95% CI, 74%-79%) for T1b or greater invasive melanoma cases. CONCLUSIONS AND RELEVANCE: Melanoma staging in AJCC 8 shows greater reproducibility and higher concordance with a reference standard. Improved classification of invasive melanoma can be expected after implementation of AJCC 8, suggesting a positive impact on patients. However, despite improvement, concordance and reproducibility remain low.

Accuracy of Digital Pathologic Analysis vs Traditional Microscopy in the Interpretation of Melanocytic Lesions.

Importance: Use of digital whole-slide imaging (WSI) for dermatopathology in general has been noted to be similar to traditional microscopy (TM); however, concern has been noted that WSI is inferior for interpretation of melanocytic lesions. Since approximately 1 of every 4 skin biopsies is of a melanocytic lesion, the use of WSI requires verification before use in clinical practice. Objective: To compare pathologists' accuracy and reproducibility in diagnosing melanocytic lesions using Melanocytic Pathology Assessment Tool and Hierarchy for Diagnosis (MPATH-Dx) categories when analyzing by TM vs WSI. Design, Setting, and Participants: A total of 87 pathologists in community-based and academic settings from 10 US states were randomized with stratification based on clinical experience to interpret in TM format 180 skin biopsy cases of melanocytic lesions, including 90 invasive melanoma, divided into 5 sets of 36 cases (phase 1). The pathologists were then randomized via stratified permuted block randomization with block size 2 to interpret cases in either TM (n = 46) or WSI format (n = 41), with each pathologist interpreting the same 36 cases on 2 separate occasions (phase 2). Diagnoses were categorized as MPATH-Dx categories I through V, with I indicating the least severe and V the most severe. Main Outcomes and Measures: Accuracy with respect to a consensus reference diagnosis and the reproducibility of repeated interpretations of the same cases. Results: Of the 87 pathologists in the study, 46% (40) were women and the mean (SD) age was 50.7 (10.2) years. Except for class III melanocytic lesions, the diagnostic categories showed no significant differences in diagnostic accuracy between TM and WSI interpretation. Discordance was lower among class III lesions for the TM interpretation arm (51%; 95% CI, 46%-57%) than for the WSI arm (61%; 95% CI, 53%-69%) (P = .05). This difference is likely to have clinical significance, because 6% of TM vs 11% of WSI class III lesions were interpreted as invasive melanoma. Reproducibility was similar between the traditional and digital formats overall (66.4%; 95% CI, 63.3%-69.3%; and 62.7%; 95% CI, 59.5%-65.7%, respectively), and for all classes, although class III showed a nonsignificant lower intraobserver agreement for digital. Significantly more mitotic figures were detected with TM compared with WSI: mean (SD) TM, 6.72 (2.89); WSI, 5.84 (2.56); P = .002. Conclusions and Relevance: Interpretive accuracy for melanocytic lesions was similar for WSI and TM slides except for class III lesions. We found no clinically meaningful differences in reproducibility for any of the diagnostic classes.

Characteristics and diagnostic performance of pathologists who enjoy interpreting melanocytic lesions.

Diagnostic discrepancy among pathologists interpreting melanocytic skin lesions (MSL) is an ongoing concern for patient care. Given that job satisfaction could impact patient care, this study aimed to characterize which pathologists enjoy interpreting MSL and estimate the association between enjoyment and diagnostic accuracy. Pathologists' demographics, training, and experience were obtained by a cross-sectional survey. Associations between these characteristics and self-reported enjoyment when interpreting MSL were estimated by Pearson's Chi-square tests. Diagnostic accuracy was determined by comparing pathologists' MSL interpretations with reference standard diagnoses. Associations between enjoyment and diagnostic accuracy were evaluated by generalized estimating equations (GEE) models. One hundred and eighty-seven (90%) pathologists completed the study. Seventy percent agreed that interpreting MSL is enjoyable. Pathologists who enjoyed interpreting MSL were more likely to be board certified and/or fellowship trained in dermatopathology (P=0.008), have ?10 years of experience (P=0.010) and have an MSL caseload of ?60 per month (P=<0.001). After adjustment, there was no association between enjoyment and diagnostic accuracy. Our data suggest that job dissatisfaction does not adversely affect diagnostic accuracy in the interpretation of melanocytic lesions, which is of importance given the progressive increase in annual biopsy rates and the attendant work demands imposed on pathologists.

Screening for Urinary Incontinence in Women: A Systematic Review for the Women's Preventive Services Initiative.

Background: Urinary incontinence is infrequently addressed during routine health care despite its high prevalence and adverse effects on health. Purpose: To evaluate whether screening for urinary incontinence in women not previously diagnosed improves outcomes (symptoms, quality of life, and function) and to evaluate the accuracy of screening methods and potential harms of screening. Data Sources: English-language searches of Ovid MEDLINE, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews (1 January 1996 to 30 March 2018); ClinicalTrials.gov (April 2018); and reference lists of studies and reviews. Study Selection: Randomized trials, cohort studies, systematic reviews of studies that enrolled nonpregnant women without previously diagnosed urinary incontinence and compared clinical outcomes and adverse effects between women who were and were not screened, and diagnostic accuracy studies that reported performance measures of screening tests. Data Extraction: Dual extraction and quality assessment of individual studies. Data Synthesis: No studies evaluated the overall effectiveness or harms of screening. Seventeen studies evaluated the diagnostic accuracy of 18 screening questionnaires against a clinical diagnosis or results of diagnostic tests. Of these, 14 poor-quality studies were based in referral clinics, enrolled only symptomatic women, or had other limitations. One good-quality and 2 fair-quality studies (evaluating 4 methods) enrolled women not recruited on the basis of symptoms. Areas under the receiver-operating characteristic curve for stress, urge, and any type of incontinence in these studies were 0.79, 0.88, and 0.88 for the Michigan Incontinence Symptom Index; 0.85, 0.83, and 0.87 for the Bladder Control Self-Assessment Questionnaire; and 0.68, 0.82, and 0.75 for the Overactive Bladder Awareness Tool. The Incontinence Screening Questionnaire had a sensitivity of 66% and specificity of 80% for any type of incontinence. Limitation: Studies enrolled few participants, often from symptomatic referral populations; used various reference standards; and infrequently reported CIs. Conclusion: Evidence is insufficient on the overall effectiveness and harms of screening for urinary incontinence in women. Limited evidence in general populations suggests fairly high accuracy for some screening methods. Primary Funding Source: Health Resources and Services Administration.

Screening for Urinary Incontinence in Women: A Recommendation From the Women's Preventive Services Initiative.

Description: Recommendation on screening for urinary incontinence in women by the Women's Preventive Services Initiative (WPSI), a national coalition of women's health professional organizations and patient representatives. The WPSI's recommendations are intended to guide clinical practice and coverage of services for the Health Resources and Services Administration and other stakeholders. The target audience for this recommendation includes all clinicians providing preventive health care for women, particularly in primary care settings. This recommendation applies to women of all ages, as well as adolescents. Methods: The WPSI developed this recommendation after evaluating evidence regarding the benefits and harms of screening for urinary incontinence in women. The evaluation included a systematic review of the accuracy of screening instruments and the benefits and harms of treatments. Indirect evidence was used to link screening and health outcomes in the chain of evidence that might support screening in the absence of direct evidence. The WPSI also considered the effect of screening on symptom progression and avoidance of costly and complex treatments, as well as implementation factors. Recommendation: The WPSI recommends screening women for urinary incontinence annually. Screening ideally should assess whether women experience urinary incontinence and whether it affects their activities and quality of life. The WPSI recommends referring women for further evaluation and treatment if indicated.

Malpractice Concerns, Defensive Medicine, and the Histopathology Diagnosis of Melanocytic Skin Lesions.

OBJECTIVES: The impact of malpractice concerns on pathologists' use of defensive medicine and interpretations of melanocytic skin lesions (MSLs) is unknown. METHODS: A total of 207 pathologists interpreting MSLs responded to a survey about past involvement in malpractice litigation, influence of malpractice concerns on diagnosis, and use of assurance behaviors (defensive medicine) to alleviate malpractice concerns. Assurance behaviors included requesting second opinions, additional slides, additional sampling, and ordering specialized tests. RESULTS: Of the pathologists, 27.5% reported that malpractice concerns influenced them toward a more severe MSL diagnosis. Nearly all (95.2%) pathologists reported practicing at least one assurance behavior due to malpractice concerns, and this practice was associated with being influenced toward a more severe MSL diagnosis (odds ratio, 2.72; 95% confidence interval, 1.41-5.26). CONCLUSIONS: One of four US skin pathologists upgrade MSL diagnosis due to malpractice concerns, and nearly all practice assurance behaviors. Assurance behaviors are associated with rendering a more severe MSL diagnosis.

Associations of Smoking, Moderate Alcohol Use, and Function: A 20-Year Cohort Study of Older Women.

Objective: The objective of this study is to determine whether the health effects of smoking and moderate alcohol use persist with aging. Method: Smoking status, alcohol use, and measures of function and health were obtained from 9,704 women aged ≥65 years at baseline and over 10- and 20-year follow-up periods. Adjusted multiple linear and logistic regression and Cox proportional hazard models estimated associations. Results: Current versus never smokers had worse walking speed, self-reported health, difficulty with instrumental activities of daily living (IADLs), and depression at 10 years and higher death rates at 10 and 20 years. Moderate versus never drinkers had better grip strength, walking speed, self-reported health, and less difficulty with IADLs and were less likely to live in nursing homes at 10 years and die at 10 and 20 years. Discussion: Among aging women over 20 years, smoking is associated with worse physical function, including death, while moderate alcohol use is associated with better outcomes.

Pathologist characteristics associated with accuracy and reproducibility of melanocytic skin lesion interpretation.

BACKGROUND: Diagnostic interpretations of melanocytic skin lesions vary widely among pathologists, yet the underlying reasons remain unclear. OBJECTIVE: Identify pathologist characteristics associated with rates of accuracy and reproducibility. METHODS: Pathologists independently interpreted the same set of biopsy specimens from melanocytic lesions on 2 occasions. Diagnoses were categorized into 1 of 5 classes according to the Melanocytic Pathology Assessment Tool and Hierarchy for Diagnosis system. Reproducibility was determined by pathologists' concordance of diagnoses across 2 occasions. Accuracy was defined by concordance with a consensus reference standard. Associations of pathologist characteristics with reproducibility and accuracy were assessed individually and in multivariable logistic regression models. RESULTS: Rates of diagnostic reproducibility and accuracy were highest among pathologists with board certification and/or fellowship training in dermatopathology and in those with 5 or more years of experience. In addition, accuracy was high among pathologists with a higher proportion of melanocytic lesions in their caseload composition and higher volume of melanocytic lesions. LIMITATIONS: Data gathered in a test set situation by using a classification tool not currently in clinical use. CONCLUSION: Diagnoses are more accurate among pathologists with specialty training and those with more experience interpreting melanocytic lesions. These findings support the practice of referring difficult cases to more experienced pathologists to improve diagnostic accuracy, although the impact of these referrals on patient outcomes requires additional research.

Pathologists' Use of Second Opinions in Interpretation of Melanocytic Cutaneous Lesions: Policies, Practices, and Perceptions.

BACKGROUND: Research examining the role of second opinions in pathology for diagnosis of melanocytic lesions is limited. OBJECTIVE: To assess current laboratory policies, clinical use of second opinions, and pathologists' perceptions of second opinions for melanocytic lesions. MATERIALS AND METHODS: Cross-sectional data collected from 207 pathologists in 10 US states who diagnose melanocytic lesions. The web-based survey ascertained pathologists' professional information, laboratory second opinion policy, use of second opinions, and perceptions of second opinion value for melanocytic lesions. RESULTS: Laboratory policies required second opinions for 31% of pathologists and most commonly required for melanoma in situ (26%) and invasive melanoma (30%). In practice, most pathologists reported requesting second opinions for melanocytic tumors of uncertain malignant potential (85%) and atypical Spitzoid lesions (88%). Most pathologists perceived that second opinions increased interpretive accuracy (78%) and protected them from malpractice lawsuits (62%). CONCLUSION: Use of second opinions in clinical practice is greater than that required by laboratory policies, especially for melanocytic tumors of uncertain malignant potential and atypical Spitzoid lesions. Quality of care in surgical interventions for atypical melanocytic proliferations critically depends on the accuracy of diagnosis in pathology reporting. Future research should examine the extent to which second opinions improve accuracy of melanocytic lesion diagnosis.