Screening for lung cancer: 2023 guideline update from the American Cancer Society.

Lung cancer is the leading cause of mortality and person-years of life lost from cancer among US men and women. Early detection has been shown to be associated with reduced lung cancer mortality. Our objective was to update the American Cancer Society (ACS) 2013 lung cancer screening (LCS) guideline for adults at high risk for lung cancer. The guideline is intended to provide guidance for screening to health care providers and their patients who are at high risk for lung cancer due to a history of smoking. The ACS Guideline Development Group (GDG) utilized a systematic review of the LCS literature commissioned for the US Preventive Services Task Force 2021 LCS recommendation update; a second systematic review of lung cancer risk associated with years since quitting smoking (YSQ); literature published since 2021; two Cancer Intervention and Surveillance Modeling Network-validated lung cancer models to assess the benefits and harms of screening; an epidemiologic and modeling analysis examining the effect of YSQ and aging on lung cancer risk; and an updated analysis of benefit-to-radiation-risk ratios from LCS and follow-up examinations. The GDG also examined disease burden data from the National Cancer Institute's Surveillance, Epidemiology, and End Results program. Formulation of recommendations was based on the quality of the evidence and judgment (incorporating values and preferences) about the balance of benefits and harms. The GDG judged that the overall evidence was moderate and sufficient to support a strong recommendation for screening individuals who meet the eligibility criteria. LCS in men and women aged 50-80 years is associated with a reduction in lung cancer deaths across a range of study designs, and inferential evidence supports LCS for men and women older than 80 years who are in good health. The ACS recommends annual LCS with low-dose computed tomography for asymptomatic individuals aged 50-80 years who currently smoke or formerly smoked and have a ≥20 pack-year smoking history (strong recommendation, moderate quality of evidence). Before the decision is made to initiate LCS, individuals should engage in a shared decision-making discussion with a qualified health professional. For individuals who formerly smoked, the number of YSQ is not an eligibility criterion to begin or to stop screening. Individuals who currently smoke should receive counseling to quit and be connected to cessation resources. Individuals with comorbid conditions that substantially limit life expectancy should not be screened. These recommendations should be considered by health care providers and adults at high risk for lung cancer in discussions about LCS. If fully implemented, these recommendations have a high likelihood of significantly reducing death and suffering from lung cancer in the United States.

Colorectal cancer statistics, 2023.

Colorectal cancer (CRC) is the second most common cause of cancer death in the United States. Every 3 years, the American Cancer Society provides an update of CRC statistics based on incidence from population-based cancer registries and mortality from the National Center for Health Statistics. In 2023, approximately 153,020 individuals will be diagnosed with CRC and 52,550 will die from the disease, including 19,550 cases and 3750 deaths in individuals younger than 50 years. The decline in CRC incidence slowed from 3%-4% annually during the 2000s to 1% annually during 2011-2019, driven partly by an increase in individuals younger than 55 years of 1%-2% annually since the mid-1990s. Consequently, the proportion of cases among those younger than 55 years increased from 11% in 1995 to 20% in 2019. Incidence since circa 2010 increased in those younger than 65 years for regional-stage disease by about 2%-3% annually and for distant-stage disease by 0.5%-3% annually, reversing the overall shift to earlier stage diagnosis that occurred during 1995 through 2005. For example, 60% of all new cases were advanced in 2019 versus 52% in the mid-2000s and 57% in 1995, before widespread screening. There is also a shift to left-sided tumors, with the proportion of rectal cancer increasing from 27% in 1995 to 31% in 2019. CRC mortality declined by 2% annually from 2011-2020 overall but increased by 0.5%-3% annually in individuals younger than 50 years and in Native Americans younger than 65 years. In summary, despite continued overall declines, CRC is rapidly shifting to diagnosis at a younger age, at a more advanced stage, and in the left colon/rectum. Progress against CRC could be accelerated by uncovering the etiology of rising incidence in generations born since 1950 and increasing access to high-quality screening and treatment among all populations, especially Native Americans.

Acquiring tissue for advanced lung cancer diagnosis and comprehensive biomarker testing: A National Lung Cancer Roundtable best-practice guide.

Advances in biomarker-driven therapies for patients with nonsmall cell lung cancer (NSCLC) both provide opportunities to improve the treatment (and thus outcomes) for patients and pose new challenges for equitable care delivery. Over the last decade, the continuing development of new biomarker-driven therapies and evolving indications for their use have intensified the importance of interdisciplinary communication and coordination for patients with or suspected to have lung cancer. Multidisciplinary teams are challenged with completing comprehensive and timely biomarker testing and navigating the constantly evolving evidence base for a complex and time-sensitive disease. This guide provides context for the current state of comprehensive biomarker testing for NSCLC, reviews how biomarker testing integrates within the diagnostic continuum for patients, and illustrates best practices and common pitfalls that influence the success and timeliness of biomarker testing using a series of case scenarios.

Human papillomavirus vaccination 2020 guideline update: American Cancer Society guideline adaptation.

The American Cancer Society (ACS) presents an adaptation of the current Advisory Committee on Immunization Practices recommendations for human papillomavirus (HPV) vaccination. The ACS recommends routine HPV vaccination between ages 9 and 12 years to achieve higher on-time vaccination rates, which will lead to increased numbers of cancers prevented. Health care providers are encouraged to start offering the HPV vaccine series at age 9 or 10 years. Catch-up HPV vaccination is recommended for all persons through age 26 years who are not adequately vaccinated. Providers should inform individuals aged 22 to 26 years who have not been previously vaccinated or who have not completed the series that vaccination at older ages is less effective in lowering cancer risk. Catch-up HPV vaccination is not recommended for adults aged older than 26 years. The ACS does not endorse the 2019 Advisory Committee on Immunization Practices recommendation for shared clinical decision making for some adults aged 27 through 45 years who are not adequately vaccinated because of the low effectiveness and low cancer prevention potential of vaccination in this age group, the burden of decision making on patients and clinicians, and the lack of sufficient guidance on the selection of individuals who might benefit.

Colorectal cancer statistics, 2020.

Colorectal cancer (CRC) is the second most common cause of cancer death in the United States. Every 3 years, the American Cancer Society provides an update of CRC occurrence based on incidence data (available through 2016) from population-based cancer registries and mortality data (through 2017) from the National Center for Health Statistics. In 2020, approximately 147,950 individuals will be diagnosed with CRC and 53,200 will die from the disease, including 17,930 cases and 3,640 deaths in individuals aged younger than 50 years. The incidence rate during 2012 through 2016 ranged from 30 (per 100,000 persons) in Asian/Pacific Islanders to 45.7 in blacks and 89 in Alaska Natives. Rapid declines in incidence among screening-aged individuals during the 2000s continued during 2011 through 2016 in those aged 65 years and older (by 3.3% annually) but reversed in those aged 50 to 64 years, among whom rates increased by 1% annually. Among individuals aged younger than 50 years, the incidence rate increased by approximately 2% annually for tumors in the proximal and distal colon, as well as the rectum, driven by trends in non-Hispanic whites. CRC death rates during 2008 through 2017 declined by 3% annually in individuals aged 65 years and older and by 0.6% annually in individuals aged 50 to 64 years while increasing by 1.3% annually in those aged younger than 50 years. Mortality declines among individuals aged 50 years and older were steepest among blacks, who also had the only decreasing trend among those aged younger than 50 years, and excluded American Indians/Alaska Natives, among whom rates remained stable. Progress against CRC can be accelerated by increasing access to guideline-recommended screening and high-quality treatment, particularly among Alaska Natives, and elucidating causes for rising incidence in young and middle-aged adults.

Cervical cancer screening for individuals at average risk: 2020 guideline update from the American Cancer Society.

The American Cancer Society (ACS) recommends that individuals with a cervix initiate cervical cancer screening at age 25 years and undergo primary human papillomavirus (HPV) testing every 5 years through age 65 years (preferred); if primary HPV testing is not available, then individuals aged 25 to 65 years should be screened with cotesting (HPV testing in combination with cytology) every 5 years or cytology alone every 3 years (acceptable) (strong recommendation). The ACS recommends that individuals aged >65 years who have no history of cervical intraepithelial neoplasia grade 2 or more severe disease within the past 25 years, and who have documented adequate negative prior screening in the prior 10 years, discontinue all cervical cancer screening (qualified recommendation). These new screening recommendations differ in 4 important respects compared with the 2012 recommendations: 1) The preferred screening strategy is primary HPV testing every 5 years, with cotesting and cytology alone acceptable where access to US Food and Drug Administration-approved primary HPV testing is not yet available; 2) the recommended age to start screening is 25 years rather than 21 years; 3) primary HPV testing, as well as cotesting or cytology alone when primary testing is not available, is recommended starting at age 25 years rather than age 30 years; and 4) the guideline is transitional, ie, options for screening with cotesting or cytology alone are provided but should be phased out once full access to primary HPV testing for cervical cancer screening is available without barriers. Evidence related to other relevant issues was reviewed, and no changes were made to recommendations for screening intervals, age or criteria for screening cessation, screening based on vaccination status, or screening after hysterectomy. Follow-up for individuals who screen positive for HPV and/or cytology should be in accordance with the 2019 American Society for Colposcopy and Cervical Pathology risk-based management consensus guidelines for abnormal cervical cancer screening tests and cancer precursors.

A blueprint for cancer screening and early detection: Advancing screening's contribution to cancer control.

From the mid-20th century, accumulating evidence has supported the introduction of screening for cancers of the cervix, breast, colon and rectum, prostate (via shared decisions), and lung. The opportunity to detect and treat precursor lesions and invasive disease at a more favorable stage has contributed substantially to reduced incidence, morbidity, and mortality. However, as new discoveries portend advancements in technology and risk-based screening, we fail to fulfill the greatest potential of the existing technology, in terms of both full access among the target population and the delivery of state-of-the art care at each crucial step in the cascade of events that characterize successful cancer screening. There also is insufficient commitment to invest in the development of new technologies, incentivize the development of new ideas, and rapidly evaluate promising new technology. In this report, the authors summarize the status of cancer screening and propose a blueprint for the nation to further advance the contribution of screening to cancer control.

Cancer screening in the United States, 2019: A review of current American Cancer Society guidelines and current issues in cancer screening.

Each year, the American Cancer Society publishes a summary of its guidelines for early cancer detection, data and trends in cancer screening rates, and select issues related to cancer screening. In this issue of the journal, the current American Cancer Society cancer screening guidelines are summarized, and the most current data from the National Health Interview Survey are provided on the utilization of cancer screening for men and women and on the adherence of men and women to multiple recommended screening tests.

Cancer screening in the United States, 2018: A review of current American Cancer Society guidelines and current issues in cancer screening.

Each year, the American Cancer Society publishes a summary of its guidelines for early cancer detection, data and trends in cancer screening rates from the National Health Interview Survey, and select issues related to cancer screening. In this 2018 update, we also summarize the new American Cancer Society colorectal cancer screening guideline and include a clarification in the language of the 2013 lung cancer screening guideline. CA Cancer J Clin 2018;68:297-316. © 2018 American Cancer Society.

Colorectal cancer screening for average-risk adults: 2018 guideline update from the American Cancer Society.

In the United States, colorectal cancer (CRC) is the fourth most common cancer diagnosed among adults and the second leading cause of death from cancer. For this guideline update, the American Cancer Society (ACS) used an existing systematic evidence review of the CRC screening literature and microsimulation modeling analyses, including a new evaluation of the age to begin screening by race and sex and additional modeling that incorporates changes in US CRC incidence. Screening with any one of multiple options is associated with a significant reduction in CRC incidence through the detection and removal of adenomatous polyps and other precancerous lesions and with a reduction in mortality through incidence reduction and early detection of CRC. Results from modeling analyses identified efficient and model-recommendable strategies that started screening at age 45 years. The ACS Guideline Development Group applied the Grades of Recommendations, Assessment, Development, and Evaluation (GRADE) criteria in developing and rating the recommendations. The ACS recommends that adults aged 45 years and older with an average risk of CRC undergo regular screening with either a high-sensitivity stool-based test or a structural (visual) examination, depending on patient preference and test availability. As a part of the screening process, all positive results on noncolonoscopy screening tests should be followed up with timely colonoscopy. The recommendation to begin screening at age 45 years is a qualified recommendation. The recommendation for regular screening in adults aged 50 years and older is a strong recommendation. The ACS recommends (qualified recommendations) that: 1) average-risk adults in good health with a life expectancy of more than 10 years continue CRC screening through the age of 75 years; 2) clinicians individualize CRC screening decisions for individuals aged 76 through 85 years based on patient preferences, life expectancy, health status, and prior screening history; and 3) clinicians discourage individuals older than 85 years from continuing CRC screening. The options for CRC screening are: fecal immunochemical test annually; high-sensitivity, guaiac-based fecal occult blood test annually; multitarget stool DNA test every 3 years; colonoscopy every 10 years; computed tomography colonography every 5 years; and flexible sigmoidoscopy every 5 years. CA Cancer J Clin 2018;68:250-281. © 2018 American Cancer Society.

Benefit-to-radiation-risk of low-dose computed tomography lung cancer screening.

BACKGROUND: The US National Lung Screening Trial (NLST) and Dutch-Belgian NELSON randomized controlled trials have shown significant mortality reductions from low-dose computed tomography (CT) lung cancer screening (LCS). NLST, ITALUNG, and COSMOS trials have provided detailed dosimetry data for LCS. METHODS: LCS trial mortality benefit results, organ dose and effective dose data, and Biological Effects of Ionizing Radiation, Report VII (BEIR VII) organ dose-to-cancer-mortality risk data are used to estimate benefit-to-radiation-risk ratios of the NLST, ITALUNG, and COSMOS trials. Data from those trials also are used to estimate benefit-to-radiation-risk ratios for longer-term LCS corresponding to scenarios recommended by United States Preventive Services Task Force and the American Cancer Society. RESULTS: Including only screening doses, NLST benefit-to-radiation-risk ratios are 12:1 for males, 19:1 for females, and 16:1 overall. Including both screening and estimated follow-up doses, benefit-to-radiation-risk ratios for NLST are 9:1 for males, 13:1 for females, and 12:1 overall. For the ITALUNG trial, the benefit-to-radiation-risk ratio is 58-63:1. For the COSMOS trial, assuming sex-specific mortality benefits like those of the NELSON trial, the benefit-to-radiation-risk ratio is 23:1. Assuming a conservative 20% mortality benefit, annual screening in people 50-79 years old with a 20+ pack-year history of smoking has benefit-to-radiation-risk ratios of 23:1 (with follow-up doses adding 40% to screening doses) to 29:1 (with follow-up adding 10%) based on COSMOS dose data. CONCLUSIONS: Based on linear, no threshold BEIR VII dose-risk estimates, benefit-to-radiation-risk ratios for LCS are highly favorable. Results emphasize the importance of using modern CT technologies, maintaining low diagnostic follow-up rates, and minimizing both screening and diagnostic follow-up doses. PLAIN LANGUAGE SUMMARY: The benefits of lung cancer screening significantly outweigh estimates of future harms associated with exposure to radiation during screening and diagnostic follow-up examinations. Our findings emphasize the importance of lung cancer screening practices using state-of-the-art computed tomography scanners and specialized low-dose lung screening and diagnostic follow-up techniques.

Assessing the impact of increasing lung screening eligibility by relaxing the maximum years-since-quit threshold: A simulation modeling study.

BACKGROUND: In 2021, the US Preventive Services Task Force expanded its lung screening recommendation to include persons aged 50-80 years who had ever smoked and had at least 20 pack-years of exposure and less than 15 years since quitting (YSQ). However, studies have suggested that screening persons who formerly smoked with longer YSQ could be beneficial. METHODS: The authors used two validated lung cancer models to assess the benefits and harms of screening using various YSQ thresholds (10, 15, 20, 25, 30, and no YSQ) and the age at which screening was stopped. The impact of enforcing the YSQ criterion only at entry, but not at exit, also was evaluated. Outcomes included the number of screens, the percentage ever screened, screening benefits (lung cancer deaths averted, life-years gained), and harms (false-positive tests, overdiagnosed cases, radiation-induced lung cancer deaths). Sensitivity analyses were conducted to evaluate the effect of restricting screening to those who had at least 5 years of life expectancy. RESULTS: As the YSQ criterion was relaxed, the number of screens and the benefits and harms of screening increased. Raising the age at which to stop screening age resulted in additional benefits but with more overdiagnosis, as expected, because screening among those older than 80 years increased. Limiting screening to those who had at least 5 years of life expectancy would maintain most of the benefits while considerably reducing the harms. CONCLUSIONS: Expanding screening to persons who formerly smoked and have greater than 15 YSQ would result in considerable increases in deaths averted and life-years gained. Although additional harms would occur, these could be moderated by ensuring that screening is restricted to only those with reasonable life expectancy.

Lung cancer statistics, 2023.

Despite decades of declining mortality rates, lung cancer remains the leading cause of cancer death in the United States. This article examines lung cancer incidence, stage at diagnosis, survival, and mortality using population-based data from the National Cancer Institute, the Centers for Disease Control and Prevention, and the North American Association of Central Cancer Registries. Over the past 5 years, declines in lung cancer mortality became considerably greater than declines in incidence among men (5.0% vs. 2.6% annually) and women (4.3% vs. 1.1% annually), reflecting absolute gains in 2-year relative survival of 1.4% annually. Improved outcomes likely reflect advances in treatment, increased access to care through the Patient Protection and Affordable Care Act, and earlier stage diagnosis; for example, compared with a 4.6% annual decrease for distant-stage disease incidence during 2013-2019, the rate for localized-stage disease rose by 3.6% annually. Localized disease incidence increased more steeply in states with the highest lung cancer screening prevalence (by 3%-5% annually) than in those with the lowest (by 1%-2% annually). Despite progress, disparities remain. For example, Native Americans have the highest incidence and the slowest decline (less than 1% annually among men and stagnant rates among women) of any group. In addition, mortality rates in Mississippi and Kentucky are two to three times higher than in most western states, largely because of elevated historic smoking prevalence that remains. Racial and geographic inequalities highlight longstanding opportunities for more concerted tobacco-control efforts targeted at high-risk populations, including improved access to smoking-cessation treatments and lung cancer screening, as well as state-of-the-art treatment.

Cancer screening in the United States, 2017: A review of current American Cancer Society guidelines and current issues in cancer screening.

Answer questions and earn CME/CNE Each year, the American Cancer Society publishes a summary of its guidelines for early cancer detection, data and trends in cancer screening rates, and select issues related to cancer screening. In this issue of the journal, the authors summarize current American Cancer Society cancer screening guidelines, describe an update of their guideline for using human papillomavirus vaccination for cancer prevention, describe updates in US Preventive Services Task Force recommendations for breast and colorectal cancer screening, discuss interim findings from the UK Collaborative Trial on Ovarian Cancer Screening, and provide the latest data on utilization of cancer screening from the National Health Interview Survey. CA Cancer J Clin 2017;67:100-121. © 2017 American Cancer Society.

Enduring Consensus Guidelines for Cervical Cancer Screening and Management: Introduction to the Scope and Process.

OBJECTIVES: The Enduring Consensus Cervical Cancer Screening and Management Guidelines (Enduring Guidelines) effort is a standing committee to continuously evaluate new technologies and approaches to cervical cancer screening, management, and surveillance. METHODS AND RESULTS: The Enduring Guidelines process will selectively incorporate new technologies and approaches with adequate supportive data to more effectively improve cancer prevention for high-risk individuals and decrease unnecessary procedures in low-risk individuals. This manuscript describes the structure, process, and methods of the Enduring Guidelines effort. Using systematic literature reviews and primary data sources, risk of precancer will be estimated and recommendations will be made based on risk estimates in the context of established risk-based clinical action thresholds. The Enduring Guidelines process will consider health equity and health disparities by assuring inclusion of diverse populations in the evidence review and risk assessment and by developing recommendations that provide a choice of well-validated strategies that can be adapted to different settings. CONCLUSIONS: The Enduring Guidelines process will allow updating existing cervical cancer screening and management guidelines rapidly when new technologies are approved or new scientific evidence becomes available.

Recommendations for Use of p16/Ki67 Dual Stain for Management of Individuals Testing Positive for Human Papillomavirus.

OBJECTIVES: The Enduring Consensus Cervical Cancer Screening and Management Guidelines Committee developed recommendations for dual stain (DS) testing with CINtec PLUS Cytology for use of DS to triage high-risk human papillomavirus (HPV)-positive results. METHODS: Risks of cervical intraepithelial neoplasia grade 3 or worse were calculated according to DS results among individuals testing HPV-positive using data from the Kaiser Permanente Northern California cohort and the STudying Risk to Improve DisparitiES study in Mississippi. Management recommendations were based on clinical action thresholds developed for the 2019 American Society for Colposcopy and Cervical Pathology Risk-Based Management Consensus Guidelines. Resource usage metrics were calculated to support decision-making. Risk estimates in relation to clinical action thresholds were reviewed and used as the basis for draft recommendations. After an open comment period, recommendations were finalized and ratified through a vote by the Consensus Stakeholder Group. RESULTS: For triage of positive HPV results from screening with primary HPV testing (with or without genotyping) or with cytology cotesting, colposcopy is recommended for individuals testing DS-positive. One-year follow-up with HPV-based testing is recommended for individuals testing DS-negative, except for HPV16- and HPV18-positive results, or high-grade cytology in cotesting, where immediate colposcopy referral is recommended. Risk estimates were similar between the Kaiser Permanente Northern California and STudying Risk to Improve DisparitiES populations. In general, resource usage metrics suggest that compared with cytology, DS requires fewer colposcopies and detects cervical intraepithelial neoplasia grade 3 or worse earlier. CONCLUSIONS: Dual stain testing with CINtec PLUS Cytology is acceptable for triage of HPV-positive test results. Risk estimates are portable across different populations.

Associations between Cerebrovascular Function and the Expression of Genes Related to Endothelial Function in Hormonal Migraine.

There is evidence to suggest that hormonal migraine is associated with altered cerebrovascular function. We aimed to investigate whether the expression of genes related to endothelial function in venous blood (1) might influence cerebrovascular function, (2) differs between hormonal migraineur and non-migraineur women, and (3) changes following resveratrol supplementation. This study utilised data obtained from 87 women (59 hormonal migraineurs and 28 controls) where RNA from venous blood was used to quantify gene expression and transcranial Doppler ultrasound was used to evaluate cerebrovascular function. Spearman's correlation analyses were performed between gene expression, cerebrovascular function, and migraine-related disability. We compared the expression of genes associated with endothelial function between migraineurs and non-migraineurs, and between resveratrol and placebo. The expression of several genes related to endothelial function was associated with alterations in cerebrovascular function. Notably, the expression of CALCA was associated with increased neurovascular coupling capacity (p = 0.013), and both CALCA (p = 0.035) and VEGF (p = 0.014) expression were associated with increased cerebral blood flow velocity in the overall study population. Additionally, VCAM1 expression correlated with decreased pulsatility index (a measure of cerebral arterial stiffness) (p = 0.009) and headache impact test-6 scores (p = 0.007) in the migraineurs. No significant differences in gene expression were observed between migraineurs and controls, or between placebo and resveratrol treatments in migraineurs. Thus, altering the expression of genes related to endothelial function may improve cerebrovascular function and decrease migraine-related disability.

Antiviral Activity of Lenacapavir Against HIV-2 Isolates and Drug-resistant HIV-2 Mutants.

The activity of lenacapavir against HIV-1 has been extensively evaluated in vitro, but comparable data for HIV-2 are scarce. We determined the anti-HIV-2 activity of lenacapavir using single-cycle infections of MAGIC-5A cells and multicycle infections of a T cell line. Lenacapavir exhibited low-nanomolar activity against HIV-2, but was 11- to 14-fold less potent against HIV-2 in comparison to HIV-1. Mutations in HIV-2 that confer resistance to other antiretrovirals did not confer cross-resistance to lenacapavir. Although lenacapavir-containing regimens might be considered for appropriate patients with HIV-2, more frequent viral load and/or CD4 testing may be needed to assess clinical response.

Exonic mutations in cell-cell adhesion may contribute to CADASIL-related CSVD pathology.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a condition caused by mutations in NOTCH3 and results in a phenotype characterised by recurrent strokes, vascular dementia and migraines. Whilst a genetic basis for the disease is known, the molecular mechanisms underpinning the pathology of CADASIL are still yet to be determined. Studies conducted at the Genomics Research Centre (GRC) have also identified that only 15-23% of individuals clinically suspected of CADASIL have mutations in NOTCH3. Based on this, whole exome sequencing was used to identify novel genetic variants for CADASIL-like cerebral small-vessel disease (CSVD). Analysis of functionally important variants in 50 individuals was investigated using overrepresentation tests in Gene ontology software to identify biological processes that are potentially affected in this group of patients. Further investigation of the genes in these processes was completed using the TRAPD software to identify if there is an increased number (burden) of mutations that are associated with CADASIL-like pathology. Results from this study identified that cell-cell adhesion genes were positively overrepresented in the PANTHER GO-slim database. TRAPD burden testing identified n = 15 genes that had a higher number of rare (MAF < 0.001) and predicted functionally relevant (SIFT < 0.05, PolyPhen > 0.8) mutations compared to the gnomAD v2.1.1 exome control dataset. Furthermore, these results identified ARVCF, GPR17, PTPRS, and CELSR1 as novel candidate genes in CADASIL-related pathology. This study identified a novel process that may be playing a role in the vascular damage related to CADASIL-related CSVD and implicated n = 15 genes in playing a role in the disease.

Breast cancer statistics, 2015: Convergence of incidence rates between black and white women.

In this article, the American Cancer Society provides an overview of female breast cancer statistics in the United States, including data on incidence, mortality, survival, and screening. Approximately 231,840 new cases of invasive breast cancer and 40,290 breast cancer deaths are expected to occur among US women in 2015. Breast cancer incidence rates increased among non-Hispanic black (black) and Asian/Pacific Islander women and were stable among non-Hispanic white (white), Hispanic, and American Indian/Alaska Native women from 2008 to 2012. Although white women have historically had higher incidence rates than black women, in 2012, the rates converged. Notably, during 2008 through 2012, incidence rates were significantly higher in black women compared with white women in 7 states, primarily located in the South. From 1989 to 2012, breast cancer death rates decreased by 36%, which translates to 249,000 breast cancer deaths averted in the United States over this period. This decrease in death rates was evident in all racial/ethnic groups except American Indians/Alaska Natives. However, the mortality disparity between black and white women nationwide has continued to widen; and, by 2012, death rates were 42% higher in black women than in white women. During 2003 through 2012, breast cancer death rates declined for white women in all 50 states; but, for black women, declines occurred in 27 of 30 states that had sufficient data to analyze trends. In 3 states (Mississippi, Oklahoma, and Wisconsin), breast cancer death rates in black women were stable during 2003 through 2012. Widening racial disparities in breast cancer mortality are likely to continue, at least in the short term, in view of the increasing trends in breast cancer incidence rates in black women.