Disentangling the relationships of body mass index and circulating sex hormone concentrations in mammographic density using Mendelian randomization.

PURPOSE: Mammographic density phenotypes, adjusted for age and body mass index (BMI), are strong predictors of breast cancer risk. BMI is associated with mammographic density measures, but the role of circulating sex hormone concentrations is less clear. We investigated the relationship between BMI, circulating sex hormone concentrations, and mammographic density phenotypes using Mendelian randomization (MR). METHODS: We applied two-sample MR approaches to assess the association between genetically predicted circulating concentrations of sex hormones [estradiol, testosterone, sex hormone-binding globulin (SHBG)], BMI, and mammographic density phenotypes (dense and non-dense area). We created instrumental variables from large European ancestry-based genome-wide association studies and applied estimates to mammographic density phenotypes in up to 14,000 women of European ancestry. We performed analyses overall and by menopausal status. RESULTS: Genetically predicted BMI was positively associated with non-dense area (IVW: ß = 1.79; 95% CI = 1.58, 2.00; p = 9.57 × 10-63) and inversely associated with dense area (IVW: ß = - 0.37; 95% CI = - 0.51,- 0.23; p = 4.7 × 10-7). We observed weak evidence for an association of circulating sex hormone concentrations with mammographic density phenotypes, specifically inverse associations between genetically predicted testosterone concentration and dense area (ß = - 0.22; 95% CI = - 0.38, - 0.053; p = 0.009) and between genetically predicted estradiol concentration and non-dense area (ß = - 3.32; 95% CI = - 5.83, - 0.82; p = 0.009), although results were not consistent across a range of MR approaches. CONCLUSION: Our findings support a positive causal association between BMI and mammographic non-dense area and an inverse association between BMI and dense area. Evidence was weaker and inconsistent for a causal effect of circulating sex hormone concentrations on mammographic density phenotypes. Based on our findings, associations between circulating sex hormone concentrations and mammographic density phenotypes are weak at best.

Reduced effectiveness of repeat influenza vaccination: distinguishing among within-season waning, recent clinical infection, and subclinical infection.

Studies have reported that prior-season influenza vaccination is associated with higher risk of clinical influenza infection among vaccinees. This effect might arise from incomplete consideration of within-season waning and recent infection. Using data from the US Flu Vaccine Effectiveness (VE) Network (2011-2012 to 2018-2019 seasons), we found that repeat vaccinees were vaccinated earlier in a season by one week. After accounting for waning VE, repeat vaccinees were still more likely to test positive for A(H3N2) (OR=1.11, 95%CI:1.02-1.21) but not for influenza B or A(H1N1). We found that clinical infection influenced individuals' decision to vaccinate in the following season while protecting against clinical infection of the same (sub)type. However, adjusting for recent clinical infections did not strongly influence the estimated effect of prior-season vaccination. In contrast, we found that adjusting for subclinical infection could theoretically attenuate this effect. Additional investigation is needed to determine the impact of subclinical infections on VE.

Breast density knowledge and willingness to delay treatment for pre-operative breast cancer imaging among women with a personal history of breast cancer.

BACKGROUND: Following a breast cancer diagnosis, it is uncertain whether women's breast density knowledge influences their willingness to undergo pre-operative imaging to detect additional cancer in their breasts. We evaluated women's breast density knowledge and their willingness to delay treatment for pre-operative testing. METHODS: We surveyed women identified in the Breast Cancer Surveillance Consortium aged ≥ 18 years, with first breast cancer diagnosed within the prior 6-18 months, who had at least one breast density measurement within the 5 years prior to their diagnosis. We assessed women's breast density knowledge and correlates of willingness to delay treatment for 6 or more weeks for pre-operative imaging via logistic regression. RESULTS: Survey participation was 28.3% (969/3,430). Seventy-two percent (469/647) of women with dense and 11% (34/322) with non-dense breasts correctly knew their density (p < 0.001); 69% (665/969) of all women knew dense breasts make it harder to detect cancers on a mammogram; and 29% (285/969) were willing to delay treatment ≥ 6 weeks to undergo pre-operative imaging. Willingness to delay treatment did not differ by self-reported density (OR:0.99 for non-dense vs. dense; 95%CI: 0.50-1.96). Treatment with chemotherapy was associated with less willingness to delay treatment (OR:0.67; 95%CI: 0.46-0.96). Having previously delayed breast cancer treatment more than 3 months was associated with an increased willingness to delay treatment for pre-operative imaging (OR:2.18; 95%CI: 1.26-3.77). CONCLUSIONS: Understanding of personal breast density was not associated with willingness to delay treatment 6 or more weeks for pre-operative imaging, but aspects of a woman's treatment experience were. CLINICALTRIALS: GOV : NCT02980848 registered December 2, 2016.

Emergency Department Use in Adolescent and Young Adult Cancer Early Survivors from 2006 to 2020.

Purpose: Understanding emergency department (ED) use in adolescent and young adult (AYA) survivors could identify gaps in AYA survivorship. Methods: We conducted a cohort study of 7925 AYA survivors (aged 15-39 years at diagnosis) who were 2-5 years from diagnosis in 2006-2020 at Kaiser Permanente Southern California. We calculated ED utilization rates overall and by indication of the encounter (headache, cardiac issues, and suicide attempts). We estimated rate changes by survivorship year and patient factors associated with ED visit using a Poisson model. Results: Cohort was 65.4% women, 45.8% Hispanic, with mean age at diagnosis at 31.3 years. Overall, 38% of AYA survivors had ≥1 ED visit (95th percentile: 5 ED visits). Unadjusted ED rates declined from 374.2/1000 person-years (PY) in Y2 to 327.2 in Y5 (p change < 0.001). Unadjusted rates declined for headache, cardiac issues, and suicide attempts. Factors associated with increased ED use included: age 20-24 at diagnosis [relative risk (RR) = 1.30, 95% CI 1.09-1.56 vs. 35-39 years]; female (RR = 1.27, 95% CI 1.11-1.47 vs. male); non-Hispanic Black race/ethnicity (RR 1.64, 95% CI 1.38-1.95 vs. non-Hispanic white); comorbidity (RR = 1.34, 95% CI 1.16-1.55 for 1 and RR 1.80, 95% CI 1.40-2.30 for 2+ vs. none); and public insurance (RR = 1.99, 95% CI 1.70-2.32 vs. private). Compared with thyroid cancer, cancers associated with increased ED use were breast (RR = 1.45, 95% CI 1.24-1.70), cervical (RR = 2.18, 95% CI 1.76-2.71), colorectal (RR = 2.34, 95% CI 1.94-2.81), and sarcoma (RR = 1.39, 95% CI 1.03-1.88). Conclusion: ED utilization declined as time from diagnosis elapsed, but higher utilization was associated with social determinants of health and cancer types.

A pragmatic randomized clinical trial of multilevel interventions to improve adherence to lung cancer screening (The Larch Study): Study protocol.

BACKGROUND: In real-world settings, low adherence to lung cancer screening (LCS) diminishes population-level benefits of reducing lung cancer mortality. We describe the Larch Study protocol, which tests the effectiveness of two patient-centered interventions (Patient Voices Video and Stepped Reminders) designed to address barriers and improve annual LCS adherence. METHODS: The Larch Study is a pragmatic randomized clinical trial conducted within Kaiser Permanente Washington. Eligible patients (target n = 1606) are aged 50-78 years with an index low-dose CT (LDCT) of the chest with negative or benign findings. With a 2 × 2 factorial-design, patients are individually randomized to 1 of 4 arms: video only, reminders only, both video and reminders, or usual care. The Patient Voices video addresses patient education needs by normalizing LCS, reminding patients when LCS is due, and encouraging social support. Stepped Reminders prompts primary care physicians to order patient's repeat screening LDCT and patients to schedule their scan. Intervention delivery is embedded within routine healthcare, facilitated by shared electronic health record components. Primary outcome is adherence to national LCS clinical guidelines, defined as repeat LDCT within 9-15 months. Patient-reported outcomes are measured via survey (knowledge of LCS, perception of stigma) approximately 8 weeks after index LDCT. Our mixed-methods formative evaluation includes process data, collected during the trial, and interviews with trial participants and stakeholders. DISCUSSION: Results will fill an important scientific gap on multilevel interventions to increase annual LCS adherence and provide opportunities for spread and scale to other healthcare settings. REGISTRATION: Trial is registered at clinicaltrials.gov (#NCT05747443).

Young Women's Perspectives on Being Screened for Hereditary Breast and Ovarian Cancer Risk During Routine Primary Care.

PURPOSE: The U.S. Preventive Services Task Force recommends screening women to identify individuals eligible for genetic counseling based on a priori hereditary breast and ovarian cancer (HBOC) risk (i.e., risk assessment). However, risk assessment has not been widely integrated into primary care. This qualitative study explored young women's views on implementing routine HBOC risk assessment with a focus on equity and patient-centeredness. METHODS: We conducted group discussions with young women (aged 21-40 years) receiving care in an integrated health care system. Discussion groups occurred in two phases and used a modified deliberative approach that included a didactic component and prioritized developing consensus. Twenty women participated in one of three initial small group discussions (phase one). All 20 were invited to participate in a subsequent large group discussion (phase two), and 15 of them attended. FINDINGS: Key themes and recommendations were as follows. Risk assessment should be accessible, contextualized, and destigmatized to encourage participation and reduce anxiety, particularly for women who do not know their family history. Providers conducting risk assessments must be equipped to address women's informational needs, relieve emotionality, and plan next steps after positive screens. Finally, to minimize differential screening uptake, health care systems must prioritize equity in program design and contribute to external educational and outreach efforts. CONCLUSION: Young women see pragmatic opportunities for health systems to optimize HBOC screening implementation.

Predicting five-year interval second breast cancer risk in women with prior breast cancer.

BACKGROUND: Annual surveillance mammography is recommended for women with a personal history of breast cancer. Risk prediction models that estimate mammography failures such as interval second breast cancers could help to tailor surveillance imaging regimens to women's individual risk profiles. METHODS: In a cohort of women with a history of breast cancer receiving surveillance mammography in the Breast Cancer Surveillance Consortium in 1996-2019, we used LASSO-penalized regression to estimate the probability of an interval second cancer (invasive cancer or ductal carcinoma in situ) in the one-year following a negative surveillance mammogram. Based on predicted risks from this one-year risk model, we generated cumulative risks of an interval second cancer for the five-year period following each mammogram. Model performance was evaluated using cross-validation in the overall cohort and within race and ethnicity strata. RESULTS: In 173,290 surveillance mammograms, we observed 496 interval cancers. One-year risk models were well-calibrated (expected/observed ratio = 1.00) with good accuracy (area under the receiver operating characteristic curve = 0.64). Model performance was similar across race and ethnicity groups. The median five-year cumulative risk was 1.20% (interquartile range 0.93-1.63%). Median five-year risks were highest in women who were under age 40 or pre- or peri-menopausal at diagnosis and those with estrogen receptor-negative primary breast cancers. CONCLUSIONS: Our risk model identified women at high risk of interval second breast cancers who may benefit from additional surveillance imaging modalities. Risk models should be evaluated to determine if risk-guided supplemental surveillance imaging improves early detection and decreases surveillance failures.

Interim Estimates of 2023-24 Seasonal Influenza Vaccine Effectiveness - United States.

In the United States, annual influenza vaccination is recommended for all persons aged ≥6 months. Using data from four vaccine effectiveness (VE) networks during the 2023-24 influenza season, interim influenza VE was estimated among patients aged ≥6 months with acute respiratory illness-associated medical encounters using a test-negative case-control study design. Among children and adolescents aged 6 months-17 years, VE against influenza-associated outpatient visits ranged from 59% to 67% and against influenza-associated hospitalization ranged from 52% to 61%. Among adults aged ≥18 years, VE against influenza-associated outpatient visits ranged from 33% to 49% and against hospitalization from 41% to 44%. VE against influenza A ranged from 46% to 59% for children and adolescents and from 27% to 46% for adults across settings. VE against influenza B ranged from 64% to 89% for pediatric patients in outpatient settings and from 60% to 78% for all adults across settings. These findings demonstrate that the 2023-24 seasonal influenza vaccine is effective at reducing the risk for medically attended influenza virus infection. CDC recommends that all persons aged ≥6 months who have not yet been vaccinated this season get vaccinated while influenza circulates locally.

Anti-SARS-CoV-2 Antibody Levels Associated with COVID-19 Protection in Outpatients Tested for SARS-CoV-2, US Flu VE Network, October 2021-June 2022.

BACKGROUND: We assessed associations between binding antibody (bAb) concentration <5 days of symptom onset and testing positive for COVID-19 among patients in a test-negative study. METHODS: From October 2021─June 2022, study sites in seven states enrolled patients aged ≥6 months presenting with acute respiratory illness. Respiratory specimens were tested for SARS-CoV-2. In blood specimens, we measured concentrations of anti-SARS-CoV-2 antibodies against the ancestral strain spike protein receptor binding domain (RBD) and nucleocapsid (N) antigens in standardized binding antibody units (BAU/mL). Percent change in odds of COVID-19 by increasing anti-RBD bAb was estimated using logistic regression as (1-adjusted odds ratio of COVID-19)x100, adjusting for COVID-19 mRNA vaccine doses, age, site, and high-risk exposure. RESULTS: Out of 2,018 symptomatic patients, 662 (33%) tested positive for acute SARS-CoV-2 infection. Geometric mean RBD bAb were lower among COVID-19 cases than SARS-CoV-2 test-negative patients during both the Delta-predominant (112 vs. 498 BAU/mL) and Omicron-predominant (823 vs. 1,189 BAU/mL) periods. Acute phase ancestral spike RBD bAb associated with 50% lower odds of COVID-19 were 1,968 BAU/mL against Delta and 3,375 BAU/mL against Omicron; thresholds may differ in other laboratories. CONCLUSION: During acute illness, antibody concentrations against ancestral spike RBD were associated with protection against COVID-19.

Unpacking the relationship between shared decision-making and decisional quality, decision to screen, and screening completion in lung cancer screening.

OBJECTIVES: Lung cancer screening is a complex and individualized decision. To understand how best to support patients in this decision, we must understand how shared decision-making is associated with both decisional and behavioral outcomes. METHODS: Observational cohort study combining patient survey data with electronic health record data of lung screening-eligible patients who recently engaged in a shared decision-making discussion about screening with a primary care clinician. RESULTS: Using multivariable analysis (n = 529), factors associated with higher lung cancer screening decisional quality include higher knowledge (OR = 1.33, p < .0001), lower perceived benefits (OR = 0.90, p = .0004), higher perceived barriers (OR = 1.07, p < .0001), higher self-efficacy (OR = 1.13, p < .0001), and higher levels of perceiving the discussion was shared (OR = 1.04, p < .0001). Factors associated with the patient's decision to screen include older age (OR = 1.12, p = .0050) and higher self-efficacy (OR = 1.11, p = .0407). Factors associated with screening completion included older age (OR = 1.05, p = .0050), higher knowledge (OR = 1.24, p = .0045), and higher self-efficacy (OR = 1.12, p = .0003). CONCLUSIONS: Shared decision-making in lung cancer screening is a dyadic process between patient and clinician. As we continue to strive for high-quality patient-centered care, patient decision quality may be enhanced by targeting key factors such as high-quality knowledge, self-efficacy, and fostering a shared discussion to support patient engagement in lung cancer screening decisions.

Late venous thromboembolism in survivors of adolescent and young adult cancer: A population-based study in California.

INTRODUCTION: Venous thromboembolism (VTE), a common complication in cancer patients, occurs more often during the initial phase of treatment. However, information on VTE beyond the first two years after diagnosis ('late VTE') is scarce, particularly in young survivors. METHODS: We examined the risk of, and factors associated with, late VTE among adolescents and young adults (AYA, 15-39 years) diagnosed with cancer (2006-2018) who survived ≥2 years. Data were obtained from the California Cancer Registry linked to hospitalization, emergency department and ambulatory surgery data. We used non-parametric models and Cox proportional hazard regression for analyses. RESULTS: Among 59,343 survivors, the 10-year cumulative incidence of VTE was 1.93 % (CI 1.80-2.07). The hazard of VTE was higher among those who had active cancer, including progression from lower stages to metastatic disease (Hazard Ratio (HR) = 10.41, 95 % confidence interval (CI): 8.86-12.22), second primary cancer (HR = 2.58, CI:2.01-3.31), or metastatic disease at diagnosis (HR = 2.38, CI:1.84-3.09). The hazard of late VTE was increased among survivors who underwent hematopoietic cell transplantation, those who received radiotherapy, had a VTE history, public insurance (vs private) or non-Hispanic Black/African American race/ethnicity (vs non-Hispanic White). Patients with leukemias, lymphomas, sarcoma, melanoma, colorectal, breast, and cervical cancers had a higher VTE risk than those with thyroid cancer. CONCLUSIONS: VTE risk remained elevated ≥2 years following cancer diagnosis in AYA survivors. Active cancer is a significant risk factor for VTE. Future studies might determine if late VTE should prompt evaluation for recurrence or second malignancy, if not already known.

Antibody response to symptomatic infection with SARS-CoV-2 Omicron variant viruses, December 2021-June 2022.

To describe humoral immune responses to symptomatic SARS-CoV-2 infection, we assessed immunoglobulin G binding antibody levels using a commercial multiplex bead assay against SARS-CoV-2 ancestral spike protein receptor binding domain (RBD) and nucleocapsid protein (N). We measured binding antibody units per mL (BAU/mL) during acute illness within 5 days of illness onset and during convalescence in 105 ambulatory patients with laboratory-confirmed SARS-CoV-2 infection with Omicron variant viruses. Comparing acute- to convalescent phase antibody concentrations, geometric mean anti-N antibody concentrations increased 47-fold from 5.5 to 259 BAU/mL. Anti-RBD antibody concentrations increased 2.5-fold from 1258 to 3189 BAU/mL.

Work Attendance with Acute Respiratory Illness Before and During COVID-19 Pandemic, United States, 2018-2022.

Both SARS-CoV-2 and influenza virus can be transmitted by asymptomatic, presymptomatic, or symptomatic infected persons. We assessed effects on work attendance while ill before and during the COVID-19 pandemic in the United States by analyzing data collected prospectively from persons with acute respiratory illnesses enrolled in a multistate study during 2018-2022. Persons with previous hybrid work experience were significantly less likely to work onsite on the day before through the first 3 days of illness than those without that experience, an effect more pronounced during the COVID-19 pandemic than during prepandemic influenza seasons. Persons with influenza or COVID-19 were significantly less likely to work onsite than persons with other acute respiratory illnesses. Among persons with positive COVID-19 test results available by the second or third day of illness, few worked onsite. Hybrid and remote work policies might reduce workplace exposures and help reduce spread of respiratory viruses.

Anti-SARS-CoV-2 Antibody Levels Associated with COVID-19 Protection in Outpatients Tested for SARS-CoV-2, US Flu VE Network, October 2021-June 2022.

Background: We assessed the association between antibody concentration ≤5 days of symptom onset and COVID-19 illness among patients enrolled in a test-negative study. Methods: From October 2021-June 2022, study sites in seven states enrolled and tested respiratory specimens from patients of all ages presenting with acute respiratory illness for SARS-CoV-2 infection using rRT-PCR. In blood specimens, we measured concentration of anti-SARS-CoV-2 antibodies against the ancestral strain spike protein receptor binding domain (RBD) and nucleocapsid (N) antigens in standardized binding antibody units (BAU/mL). Percent reduction in odds of symptomatic COVID-19 by anti-RBD antibody was estimated using logistic regression modeled as (1-adjusted odds ratio of COVID-19)×100, adjusting for COVID-19 vaccination status, age, site, and high-risk exposure. Results: A total of 662 (33%) of 2,018 symptomatic patients tested positive for acute SARS-CoV-2 infection. During the Omicron-predominant period, geometric mean anti-RBD binding antibody concentrations measured 823 BAU/mL (95%CI:690-981) among COVID-19 case-patients versus 1,189 BAU/mL (95%CI:1,050-1,347) among SARS-CoV-2 test-negative patients. In the adjusted logistic regression, increasing levels of anti-RBD antibodies were associated with reduced odds of COVID-19 for both Delta and Omicron infections. Conclusion: Higher anti-RBD antibodies in patients were associated with protection against symptomatic COVID-19 during emergence of SARS-CoV-2 Delta and Omicron variants.

Incidence and Survival for Patients Diagnosed With Breast, Colorectal, and Lung Cancer in an Integrated System.

INTRODUCTION: Documenting trends in cancer incidence and survival is a national priority. This study estimated age- and sex-adjusted incidence and 5-year relative survival among patients with cancer diagnosed within Kaiser Permanente compared to Surveillance, Epidemiology, and End Results (SEER) estimates. METHODS: The cohort included Kaiser Permanente health plan members diagnosed with breast (BC), colorectal (CRC), or lung cancer (LC) between January 1, 1999 and December 31, 2018. Incidence was computed as age-adjusted rates per 100,000 member-years. SEER*Stat was used to compute 5-year relative survival. RESULTS: Kaiser Permanente BC incidence rates were persistently higher than SEER from 2004 (126.5 [95% confidence interval (CI) = 123.2-129.9] vs 122.6 [95% CI = 121.3-123.2]) through 2013 (132.06 [95% CI = 129.5-135.7] vs 126.7 [95% CI = 125.9-127.5]). Kaiser Permanente CRC and LC incidence rates were lower than SEER for all years except 2008, showing a spike in CRC incidence (51.5 [95% CI = 49.9-53.0] vs 46.1 [95% CI = 45.7-46.4]). Kaiser Permanente BC, CRC, and LC survival estimates for all stages were higher than SEER. CONCLUSIONS: Incidence rates for all-stage and localized-stage BC were consistently higher for Kaiser Permanente than for SEER. CRC and LC rates were lower. Kaiser Permanente survival rates were consistently higher than for SEER. The strengths of these findings are associated with the ability to capture "gold-standard" cancer registry data on defined Kaiser Permanente populations. However, findings should be interpreted cautiously given differences in the underlying populations and secular and regional differences between Kaiser Permanente and SEER. The Kaiser Permanente population is younger and more racially diverse than SEER aggregate populations, and Kaiser Permanente members are insured with access to preventive care (eg, smoking cessation programs, cancer screening).

Challenges and Opportunities of Epidemiological Studies to Reduce the Burden of Cancers in Young Adults.

There are >1.9 million survivors of adolescent and young adult cancers (AYA, diagnosed at ages 15-39) living in the U.S. today. Epidemiologic studies to address the cancer burden in this group have been a relatively recent focus of the research community. In this article, we discuss approaches and data resources for cancer epidemiology and health services research in the AYA population. We consider research that uses data from cancer registries, vital records, healthcare utilization, and surveys, and the accompanying challenges and opportunities of each. To illustrate the strengths of each data source, we present example research questions or areas that are aligned with these data sources and salient to AYAs. Integrating the respective strengths of cancer registry, vital records, healthcare data, and survey-based studies sets the foundation for innovative and impactful research on AYA cancer treatment and survivorship to inform a comprehensive understanding of diverse AYA needs and experiences.

Impact of Surveillance Mammography Intervals Less Than One Year on Performance Measures in Women With a Personal History of Breast Cancer.

OBJECTIVE: When multiple surveillance mammograms are performed within an annual interval, the current guidance for one-year follow-up to determine breast cancer status results in shared follow-up periods in which a single breast cancer diagnosis can be attributed to multiple preceding examinations, posing a challenge for standardized performance assessment. We assessed the impact of using follow-up periods that eliminate the artifactual inflation of second breast cancer diagnoses. MATERIALS AND METHODS: We evaluated surveillance mammograms from 2007-2016 in women with treated breast cancer linked with tumor registry and pathology outcomes. Second breast cancers included ductal carcinoma in situ or invasive breast cancer diagnosed during one-year follow-up. The cancer detection rate, interval cancer rate, sensitivity, and specificity were compared using different follow-up periods: standard one-year follow-up per the American College of Radiology versus follow-up that was shortened at the next surveillance mammogram if less than one year (truncated follow-up). Performance measures were calculated overall and by indication (screening, evaluation for breast problem, and short interval follow-up). RESULTS: Of 117971 surveillance mammograms, 20% (n = 23533) were followed by another surveillance mammogram within one year. Standard follow-up identified 1597 mammograms that were associated with second breast cancers. With truncated follow-up, the breast cancer status of 179 mammograms (11.2%) was revised, resulting in 1418 mammograms associated with unique second breast cancers. The interval cancer rate decreased with truncated versus standard follow-up (3.6 versus 4.9 per 1000 mammograms, respectively), with a difference (95% confidence interval [CI]) of -1.3 (-1.6, -1.1). The overall sensitivity increased to 70.4% from 63.7%, for the truncated versus standard follow-up, with a difference (95% CI) of 6.6% (5.6%, 7.7%). The specificity remained stable at 98.1%. CONCLUSION: Truncated follow-up, if less than one year to the next surveillance mammogram, enabled second breast cancers to be associated with a single preceding mammogram and resulted in more accurate estimates of diagnostic performance for national benchmarks.

Longitudinal adherence to breast cancer surveillance following cancer genetic testing in an integrated health care system.

PURPOSE: Screening with mammography and breast magnetic resonance imaging (MRI) is an important risk management strategy for individuals with inherited pathogenic variants (PVs) in genes associated with increased breast cancer risk. We describe longitudinal screening adherence in individuals who underwent cancer genetic testing as part of usual care in a vertically integrated health system. METHODS: We determined the proportion time covered (PTC) by annual mammography and breast MRI for individuals with PVs in TP53, BRCA1, BRCA2, PALB2, NF1, CHEK2, and ATM. We determined time covered by biennial mammography beginning at age 50 years for individuals who received negative results, uncertain results, or with PVs in genes without specific breast cancer screening recommendations. RESULTS: One hundred and forty individuals had PVs in TP53, BRCA1, BRCA2, PALB2, NF1, CHEK2, or ATM. Among these individuals, average PTC was 48% (range 0-99%) for annual screening mammography and 34% (range 0-100%) for annual breast MRI. Average PTC was highest for individuals with PVs in CHEK2 (N = 14) and lowest for individuals with PVs in TP53 (N = 3). Average PTC for biennial mammography (N = 1,027) was 49% (0-100%). CONCLUSION: Longitudinal screening adherence in individuals with PVs in breast cancer associated genes, as measured by the proportion of time covered, is low; adherence to annual breast MRI falls below that of annual mammography. Additional research should examine screening behavior in individuals with PVs in breast cancer associated genes with a goal of developing interventions to improve adherence to recommended risk management.

Prior SARS-CoV-2 infection and COVID-19 vaccine effectiveness against outpatient illness during widespread circulation of SARS-CoV-2 Omicron variant, US Flu VE network.

BACKGROUND: We estimated combined protection conferred by prior SARS-CoV-2 infection and COVID-19 vaccination against COVID-19-associated acute respiratory illness (ARI). METHODS: During SARS-CoV-2 Delta (B.1.617.2) and Omicron (B.1.1.529) variant circulation between October 2021 and April 2022, prospectively enrolled adult patients with outpatient ARI had respiratory and filter paper blood specimens collected for SARS-CoV-2 molecular testing and serology. Dried blood spots were tested for immunoglobulin-G antibodies against SARS-CoV-2 nucleocapsid (NP) and spike protein receptor binding domain antigen using a validated multiplex bead assay. Evidence of prior SARS-CoV-2 infection also included documented or self-reported laboratory-confirmed COVID-19. We used documented COVID-19 vaccination status to estimate vaccine effectiveness (VE) by multivariable logistic regression by prior infection status. RESULTS: Four hundred fifty-five (29%) of 1577 participants tested positive for SARS-CoV-2 infection at enrollment; 209 (46%) case-patients and 637 (57%) test-negative patients were NP seropositive, had documented previous laboratory-confirmed COVID-19, or self-reported prior infection. Among previously uninfected patients, three-dose VE was 97% (95% confidence interval [CI], 60%-99%) against Delta, but not statistically significant against Omicron. Among previously infected patients, three-dose VE was 57% (CI, 20%-76%) against Omicron; VE against Delta could not be estimated. CONCLUSIONS: Three mRNA COVID-19 vaccine doses provided additional protection against SARS-CoV-2 Omicron variant-associated illness among previously infected participants.