Sanford Health is a non-profit, integrated health care delivery system, with its headquarters in Sioux Falls, South Dakota, with additional offices in Fargo and Bismarck, North Dakota, and Bemidji, Minnesota.
Importance:Individual breast cancer risk can guide screening initiation, frequency, use of supplemental imaging, and preventive measures to improve breast cancer screening by shifting resources from low-risk women to high-risk women. Objective:To determine whether risk-based breast cancer screening is a feasible alternative to annual mammography. Design, Setting, and Participants:Parallel-group, pragmatic, multicenter randomized clinical trial comparing risk-based (n = 14 212) with annual (n = 14 160) breast cancer screening. Women aged 40 to 74 years without prior diagnoses of breast cancer or ductal carcinoma in situ, or prophylactic bilateral mastectomy, were recruited from all 50 US states from September 2016 to February 2023, with follow-up through September 5, 2025 (median follow-up, 5.1 years). Statistical analysis was conducted between July and November 2025. All study procedures were conducted via an online platform. Women who declined randomization were enrolled in an observational cohort. Interventions:Risk assessment included sequencing of 9 susceptibility genes, polygenic risk score, and the Breast Cancer Surveillance Consortium version 2 model. The risk-based group received 1 of 4 recommendations: (1) highest risk (≥6% 5-year risk, high-penetrance pathogenic variant): alternating mammography and magnetic resonance imaging (MRI) every 6 months and counseling; (2) elevated risk (top 2.5 risk percentile by age): annual mammography and risk-reduction counseling; (3) average risk: biennial mammography; and (4) low risk (aged 40-49 years and <1.3% 5-year risk): no screening until risk is 1.3% or greater or age 50 years. Main Outcomes and Measures:The coprimary outcomes included noninferiority for stage ≥IIB cancers and superiority in reducing biopsy rates. Secondary outcomes included identification of stage ≥IIA cancers, mammogram rates, uptake of prevention strategies in higher risk cohorts, preference for screening group in the observational cohort, ductal carcinoma in situ, MRI, and stage-specific cancer rates. Results:A total of 28 372 women were randomized. The mean (SD) age was 54 (9.6) years and the majority were non-Hispanic White (77%). The rate of stage ≥IIB cancers was noninferior in the risk-based compared with the annual group (risk-based: 30.0 [95% CI, 16.3-43.8] vs annual: 48.0 [95% CI, 30.1-65.5] per 100 000 person-years; rate difference, -18.0 per 100 000 person-years [95% CI, -40.2 to 4.1]). The rate of breast biopsies was not lower in the risk-based group (rate difference, 98.7 per 100 000 person-years [95% CI, -17.9 to 215.3]) despite fewer mammograms (rate difference, -3835.9 [95% CI, -4516.8 to -3154.9]). The cumulative incidence of cancer, biopsy, mammogram, and MRI increased as risk category increased. In the observational cohort, 89% of participants (15 980/18 031) chose risk based. Conclusions:Risk-based breast cancer screening that includes population-based genetic testing safely stratified risk and screening intensity, but did not reduce biopsy rates. Trial Registration:ClinicalTrials.gov Identifier: NCT02620852.
Our study aimed to determine if chemotherapy administration based on the 21-gene Oncotype DX Recurrence Score (RS) in men with hormone receptor positive (HR+) Her2 negative (Her2-) lymph node positive(LN+) breast cancers (BC) impacted overall survival (OS). We conducted a retrospective cohort study on adult men and women with HR+ Her2-, 1–3 axillary LN + BC, with a valid oncotype DX RS assay, diagnosed between the years 2004–2020, using the National Cancer Database. RS risk categories were defined as low risk: 0–13, intermediate risk:14–25, and high risk: ≥26. Of the 77,820 patients included in the study, 900 (1.2
Background Some unprofessional behaviours, including allegations of discrimination, hostile work environment, violent behaviour, sexual boundary violations, potentially impaired clinicians, professional integrity and retaliation, require healthcare organisations to have a timely and reliable process to guide investigation, inquiry and/or interventions. Failure to have a consistent approach creates extraordinary risk for organisations, their team members and their patients. Methods Descriptive study of five health systems that participate in a national professionalism collaborative through the Vanderbilt Health Center for Patient and Professional Advocacy (CPPA) and implemented a huddle process to guide the initial disposition of event reports describing unprofessional behaviours that might warrant investigation, inquiry or intervention. Each site applied lessons learnt over the study period to refine the huddle participants, the process for the huddle and the tracking of information based on their experience. Results During the study, the participating sites held 219 huddles, which represented <1% of reports processed by CPPA during the study period. The most common type of reports resulting in a huddle included allegations of discrimination (30% of huddles) or hostile work environment (29%). Other common reasons for huddles included violent or aggressive behaviour (15%) or potential sexual boundary violations (13%). Additional reasons for huddles included concerns for an impaired clinician (3%), integrity (2%) or retaliation against a reporter for a previous electronic safety event report (2%). Conclusions Implementing a huddle to review and guide next steps for reports including allegations of serious behaviours provided the healthcare organisations a process to reduce the variability of response to such reports and fostered increased communication and trust among organisational key stakeholders.
Importance:The management of patent ductus arteriosus (PDA) in preterm infants is controversial. Objective:To determine whether expectant management compared with active treatment of a protocol-defined PDA in preterm infants decreases the incidence of death or bronchopulmonary dysplasia (BPD). Design, Setting, and Participants:A randomized clinical trial including infants born at 22 to 28 weeks' gestation and diagnosed with a protocol-defined PDA between the age of 48 hours and 21 days at screening. The trial was conducted from December 2018 to December 2024 at 33 hospitals within the National Institute of Child Health and Human Development Neonatal Research Network. The final date of follow-up was June 2025. Interventions:Infants with PDA were randomized to expectant management (n = 242) or active treatment (n = 240; acetaminophen, ibuprofen, or indomethacin) to close the PDA. Main Outcomes and Measures:The primary outcome was death or BPD at 36 weeks' postmenstrual age. The secondary outcomes included the components of the primary outcome and other morbidities of prematurity. Results:A total of 482 infants were randomized (median gestational age, 25 weeks [IQR, 24 to 27 weeks]; median birth weight, 760 g [IQR, 620 to 935 g]). The trial was stopped for futility and safety after the 50% interim analysis for the primary outcome due to higher survival in the expectant management group. The incidence of death or BPD was 80.9% (195/241) of infants in the expectant management group vs 79.6% (191/240) of infants in the active treatment group (adjusted risk difference, 1.2% [95% CI, -5.7% to 8.1%]; P = .73). The incidence of death before 36 weeks' postmenstrual age was 4.1% (10/241) of infants in the expectant management group vs 9.6% (23/240) of infants in the active treatment group (adjusted risk difference, -5.6% [95% CI, -10.1% to -1.2%]; P = .01). Infections resulting in death occurred in 0.8% (2/241) of infants in the expectant management group vs 3.8% (9/240) of infants in the active treatment group. Conclusions and Relevance:In extremely preterm infants with a protocol-defined PDA, death or BPD did not differ between the expectant management group and the active treatment group. Survival was substantially higher with expectant management. Trial Registration:ClinicalTrials.gov Identifier: NCT03456336.
Importance:The prevalence of pathogenic or likely pathogenic variants (PVs) in breast cancer susceptibility genes in the US population-regardless of family history risk factors-remains largely unknown because population-based genetic screening is not routinely performed. Objective:To identify the prevalence of PVs in a large cohort of women offered criteria-independent genetic testing and to evaluate the relationship of test positivity to family history and other patient characteristics. Design, Setting, and Participants:The Women Informed to Screen Depending on Measures of Risk (WISDOM) randomized clinical trial enrolled women without breast cancer aged 40 to 74 years between August 2016 and February 2023 in a pragmatic randomized screening trial comparing annual screening mammography with personalized risk-based screening. Data were analyzed from August 2023 to November 2025. Exposures:All women in the personalized screening arm were offered germline testing for 9 breast cancer susceptibility genes: BRCA1, BRCA2, ATM, CHEK2, PALB2, CDH1, PTEN, STK11, and TP53. Main Outcomes and Measures:The prevalence of PVs in the trial and the distribution of self-reported demographic and family history data in this subpopulation of carriers. Results:Among 23 098 women who completed germline genetic testing (mean [SD] age, 54.3 [9.6] years), 714 (3.1%) carried a PV. Excluding 109 who were previously aware of their PV, the detection rate was 2.6%. PVs were most common in CHEK2 (337 [1.5%]) and ATM (101 [0.4%]) but less common in higher-penetrance genes (BRCA1, 33 [0.1%]; BRCA2, 82 [0.4%]; PALB2, 44 [0.2%]). PVs in the CDH1, PTEN, STK11, and TP53 genes were rare (less than 0.1%). Notably, 180 of 605 women with PVs (29.8%) did not report a first-degree or second-degree female relative with breast or ovarian cancer, male relative with breast cancer, or Jewish ancestry. Conclusions and Relevance:In this secondary analysis of the WISDOM trial, criteria-independent genetic testing in a pragmatic trial identified a substantial number of women with clinically actionable results, many of whom would not have qualified for genetic testing under current guidelines. These findings support broader access to genetic testing as part of personalized breast cancer risk assessment. Trial Registration:ClinicalTrials.gov Identifier: NCT02620852.
