JAMA Internal Medicine

Germline Pathogenic Variants Among Women Without a History of Breast Cancer

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

Patient Navigation Services for Breast and Cervical Cancer Screening and Follow-Up

ImportanceScreening and follow-up rates for breast and cervical cancer vary across socioeconomic and demographic groups. While patient navigation services can help patients overcome barriers to health care, they are not commonly used in cancer screening.ObjectiveTo determine the effectiveness and harms of patient navigation services to increase screening and follow-up rates for breast and cervical cancer.Data SourcesA search of the MEDLINE, Scopus, CENTRAL, and Cochrane Database of Systematic Reviews was conducted for English-language articles published between January 1, 2000, and September 19, 2024. A manual review of article references supplemented the search.Study SelectionEligible articles were randomized clinical trials comparing the effectiveness of patient navigation services in participants eligible for breast or cervical cancer screening with usual care or control groups, as well as observational studies for harm. Investigators independently dual-reviewed abstracts and full-text articles to identify studies meeting prespecified eligibility criteria. Disagreements were resolved by consensus with a third reviewer. Of all abstracts and full-text articles reviewed, 2.9% were selected for analysis.Data Extraction and SynthesisThis report followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. A single investigator extracted data from each study. A second investigator reviewed the data for accuracy. Investigators independently dual-rated individual study quality as good, fair, or poor. Discordant quality ratings were resolved with a third reviewer. Data were combined using a profile likelihood random-effects model.Main Outcomes and MeasuresThe main outcomes were breast and cervical cancer screening rates within 1 year of the intervention, follow-up rates within 2 years, and any harm.ResultsA total of 42 randomized clinical trials with 39 111 participants assessing the effectiveness of patient navigation services to increase screening and follow-up rates for breast and cervical cancer were included in the meta-analysis; no studies described harms. For breast cancer, patient navigation resulted in higher rates of screening (risk ratio [RR], 1.50; 95% CI, 1.30-1.75; I2 = 88.0%; 30 trials; n = 34 744 participants) and follow-up (RR, 1.23; 95% CI, 1.15-1.41; I2 = 12.6%; 3 trials; n = 1008 participants) compared with comparison groups. For cervical cancer, patient navigation also resulted in higher rates of screening (RR, 1.62; 95% CI, 1.28-2.09; I2 = 89.6%; 20 trials; n = 11 820 participants) and follow-up (RR, 1.63; 95% CI, 0.86-2.65; I2 = 69.0%; 2 trials; n = 401 participants). Sensitivity analyses demonstrated higher screening rates with patient navigation vs comparison groups for general populations and populations based on race, ethnicity, low-income status, and other characteristics. Predicted 1-year absolute rates following patient navigation were 13.8% higher for breast cancer screening and 15.6% higher for cervical cancer screening than for comparison groups.Conclusions and RelevanceThe results of this systematic review and meta-analysis suggest that patient navigation services can increase breast and cervical cancer screening and follow-up. Reducing barriers with patient navigation services could improve access and engage patients in more effective and equitable cancer preventive care.

National Breast, Cervical, and Colorectal Cancer Screening Use in Federally Qualified Health Centers

ImportanceFederally qualified health centers (FQHCs) deliver health care to nearly 30 million underserved persons across the US, yet nationwide and state-level breast, cervical, and colorectal cancer screening use in FQHCs is not described. Furthermore, it is unknown how the underscreened FQHC population contributes to the total underscreened population at national and state levels.ObjectiveTo describe national- and state-level breast, cervical, and colorectal cancer screening use among individuals served by FQHCs in the US and to estimate the percentage of underscreened individuals in the general population served by FQHCs.Design, Setting, and ParticipantsThis cross-sectional analysis of cancer screening used data from January 1 through December 31, 2020, from the FQHC Uniform Data System, reported by 1364 FQHCs across the US, and self-reported estimates from the Behavioral Risk Factor Surveillance System. Participants were 16 696 692 US adults served by FQHCs who were eligible for breast (age, 50-74 years), cervical (age, 21-64 years), and colorectal (age, 50-75 years) cancer screening. Analyses were conducted between January 1 and June 30, 2023.ExposuresBreast, cervical, and colorectal cancer screening.Main Outcomes and MeasuresPercentages of breast, cervical, and colorectal cancer screening-eligible individuals up to date on screening.ResultsA total of 3 162 882 breast, 7 444 465 cervical, and 6 089 345 colorectal screening–eligible individuals were served by FQHCs in 2020. Nationally, screening use in FQHCs was 45.4% (95% CI, 45.4%-45.5%) for breast cancer, 51.0% (95% CI, 51.0%-51.1%) for cervical cancer, and 40.2% (95% CI, 40.1%-40.2%) for colorectal cancer. Screening use among the US general population was 78.2% (95% CI, 77.6%-78.9%) for breast cancer, 82.9% (95% CI, 82.3%-83.4%) for cervical cancer, and 72.3% (95% CI, 71.7%-72.8%) for colorectal cancer. The contribution of the underscreened population served by FQHCs to the national underscreened general population was 16.9% (95% uncertainty interval [UI], 16.4%-17.4%) for breast cancer, 29.7% (95% UI, 28.8%-30.7%) for cervical cancer, and 14.7% (95% UI, 14.4%-15.0%) for colorectal cancer.Conclusions and RelevanceFindings from this national cross-sectional study indicated major gaps in cancer screening use in FQHCs in the US. Improved prevention is urgently needed to address screening disparities.

The Dangers of Using Tumor Markers to Evaluate Nonspecific Symptoms

Prevalence of Potentially Unnecessary Bimanual Pelvic Examinations and Papanicolaou Tests Among Adolescent Girls and Young Women Aged 15-20 Years in the United States

Pelvic examination is no longer recommended for asymptomatic, nonpregnant women and may cause harms such as false-positive test results, overdiagnosis, anxiety, and unnecessary costs. The bimanual pelvic examination (BPE) is an invasive and controversial examination component. Cervical cancer screening is not recommended for women younger than 21 years. To estimate prevalence of potentially unnecessary BPE and Papanicolaou (Pap) tests performed among adolescent girls and women younger than 21 years (hereinafter referred to as young women) in the United States and to identify factors associated with receiving these examinations. A cross-sectional analysis of the National Survey of Family Growth from September 2011 through September 2017 focused on a population-based sample of young women aged 15 to 20 years (n = 3410). The analysis used survey weights to estimate prevalence and the number of people represented in the US population. Data were analyzed from December 21, 2018, through September 3, 2019. Receipt of a BPE or a Pap test in the last 12 months and the proportion of potentially unnecessary examinations and tests. Responses from 3410 young women aged 15 to 20 years were included in the analysis with 6-year sampling weights applied. Among US young women aged 15 to 20 years represented during the 2011-2017 study period, 4.8% (95% CI, 3.9%-5.9%) were pregnant, 22.3% (95% CI, 20.1%-24.6%) had undergone STI testing, and 4.5% (95% CI, 3.6%-5.5%) received treatment or medication for an STI in the past 12 months (Table 1). Only 2.0% (95% CI, 1.4%-2.9%) reported using an IUD, and 33.5% (95% CI, 30.8%-36.4%) used at least 1 other type of hormonal contraception in the past 12 months. Among US young women aged 15 to 20 years who were surveyed in the years 2011 through 2017, approximately 2.6 million (22.9%; 95% CI, 20.7%-25.3%) reported having received a BPE in the last 12 months. Approximately half of these examinations (54.4%; 95% CI, 48.8%-59.9%) were potentially unnecessary, representing an estimated 1.4 million individuals. Receipt of a BPE was associated with having a Pap test (adjusted prevalence ratio [aPR], 7.12; 95% CI, 5.56-9.12), testing for sexually transmitted infections (aPR, 1.60; 95% CI, 1.34-1.90), and using hormonal contraception other than an intrauterine device (aPR, 1.31; 95% CI, 1.11-1.54). In addition, an estimated 2.2 million young women (19.2%; 95% CI, 17.2%-21.4%) reported having received a Pap test in the past 12 months, and 71.9% (95% CI, 66.0%-77.1%) of these tests were potentially unnecessary. This analysis found that more than half of BPEs and almost three-quarters of Pap tests performed among young women aged 15 to 20 years during the years 2011 through 2017 were potentially unnecessary, exposing women to preventable harms. The results suggest that compliance with the current professional guidelines regarding the appropriate use of these examinations and tests may be lacking.

Self-Collection for Cervical Cancer Screening in a Safety-Net Setting

ImportanceThere are limited data on the effectiveness of mailed self-collection to increase cervical cancer screening (CCS) participation in underresourced health care settings.ObjectiveTo compare the effectiveness of mailed self-collection kits, with and without patient navigation, to telephone reminders to increase CCS in a safety-net health system.Design, Setting, and ParticipantsThis pragmatic, parallel, single-blinded, randomized clinical trial within a publicly funded safety-net health system in Houston, Texas, compared (1) telephone reminder (TR) for clinic-based screening, (2) TR with mailed self-collection (SC), and (3) TR with mailed SC and patient navigation among a random sample of CCS-eligible patients not up to date with CCS, including those with no CCS on record. The trial was conducted from February 20, 2020, to August 31, 2023.InterventionsAll groups received a TR by a patient navigator to attend clinic-based CCS. In the SC and SC with patient navigation groups, participants were additionally mailed a self-collection kit to their home as an alternative to clinic-based CCS. In the SC with patient navigation group, the mailed kit was followed by a patient navigation telephone call.Main Outcomes and MeasuresCCS participation was defined as attendance for clinic-based screening or return of a mailed self-collection kit within 6 months of randomization and determined through electronic health record review.ResultsOf the 2474 participants in the intent-to-screen analyses (median [IQR] age, 49 [39-57] years), 2325 (94.0%) were from racial or ethnic minoritized populations (1655 [66.9%] identifying as Hispanic or Latino, 82 [3.3%] as non-Hispanic Asian, 535 [21.6%] as non-Hispanic Black or African American, and 53 [2.1%] as other or unknown race, including American Indian or Alaska Native and Native Hawaiian or Other Pacific Islander), and 1388 (56.1%) were covered by the county’s publicly funded financial assistance program. At 6 months, 144 of 828 participants (17.4%) in the TR group, 340 of 828 (41.1%) in the SC group, and 381 of 818 (46.6%) in the SC with patient navigation group had participated in CCS. Compared to TR, relative participation was 2.36 (95% CI, 1.99-2.80) times higher for SC and 2.68 (95% CI, 2.27-3.16) times higher for SC with patient navigation; screening difference was 23.7% (95% CI, 19.4%-27.9%) for SC and 29.2% (95% CI, 24.9%-33.5%) for SC with patient navigation.Conclusions and RelevanceIn this randomized clinical trial in a safety-net health system, SC was effective for increasing CCS participation among underscreened patients; there were modest additional gains from SC with patient navigation. The large increase in CCS participation using SC compared to TR suggest that SC should be considered in safety-net settings with suboptimal CCS coverage.Trial RegistrationClinicalTrials.gov Identifier: NCT03898167