Trends in Breast Cancer Mortality Among Elderly Males in the United States (1999–2020): A CDC WONDER Analysis

Trends in Breast Cancer Mortality Among Elderly Males in the United States (1999–2020): A CDC WONDER Analysis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Trends in Breast Cancer Mortality Among Elderly Males in the United States (1999–2020): A CDC WONDER Analysis Rawdah Shakil, Sabin Zafar, Momina Javed, Shahzaib Khan, Fatima Najam, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7040692/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purpose: While male breast cancer (MBC) is rare, existing studies often exclude elderly males or lack detailed analysis by demographic and geographic factors. Our purpose was to evaluate mortality trends in elderly males (≥65 years) with breast cancer from 1999–2020 by various demographics Methodology: Death certificate data (1999-2020) from the CDC WONDER database were examined for MBC-related mortality in males aged ≥65 years using ICD-10 codes, C50.0 to C50.9. Age-adjusted mortality rates (AAMR) per million persons (95% CIs) were calculated, and the Joinpoint Regression model was used to calculate the annual percentage change (APC). Results: The overall APC was -1.29 (95% CI: -1.85 to -0.71), and a total of 8780 deaths from 1999 to 2020 were reported. The AAMR decreased from 25.0 in 1999 to 23.0 in 2020 for non-Hispanic White elderly males, marking a significant drop of 1.22% (95% CI:-1.76 to -0.65)in mortality per year. In contrast, annual mortality among non-Hispanic Black or African American patients showed a non-significant decrease of 0.71% (95% CI: -2.06 to -0.88). Geographically, the highest total AAMRs were observed in rural areas, the Northeast region, and Rhode Island, while the lowest in urban areas, the West, and Hawaii. Conclusion: Overall mortality has significantly dropped over the last two decades. The disparity between the races may be attributed to various factors such as genetic differences and socioeconomic factors. These results highlight the need for further research into the observed disparities and for more screening, public awareness, and male-oriented clinical trials. CDC Wonder Male breast cancer Mortality Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 INTRODUCTION Male breast cancer (MBC) typically presents with nipple retraction or painless subareolar masses [ 1 ]. The risk factors include family history, hormonal imbalances such as an excess of estrogen and low production of androgens, alcohol consumption, and radiation exposure. Family history is usually linked to genetic mutations in the high-penetrance genes, BRCA1 and BRCA2 [ 2 ]. Individuals with BRCA2 mutations have an estimated 6.9% lifetime risk of developing breast cancer, which is approximately 80 to 100 times higher than the general population [ 3 ]. In addition, the majority of tumors among men are estrogen receptor-positive [ 1 ]. In the USA, about 1 out of every 100 breast cancers diagnosed in the United States is found in a man and it is estimated that approximately 2,300 new cases and 500 associated deaths were reported in 2017, accounting for approximately 1% of all breast cancers [ 4 ]. The incidence of invasive breast cancer in men is 1.28 per 100,000 and increases with age. Those aged 80 years and over (the elderly) have an incidence of about 8.30, with a mortality rate of 2.68 per 100,000 men[ 4 ]. Furthermore, the 5- and 10-year unadjusted survival rates for MBC were 77.7% and 60.7%, respectively, from 2004 to 2015 based on data from the National Cancer Database [ 5 ]. Additionally, older males have advanced and aggressive cancer features such as a higher frequency of metastatic spread to lymph nodes, higher rates of stage III and IV disease, and larger sizes of tumors [ 6 ]. However, there is a delay in the presentation which is due to the lack of awareness and absence of targeted screening mammograms for men which leads to the development of widespread advanced disease and higher mortality as compared to females [ 7 ]. The development of novel treatment options, clinical trials, literature, and awareness campaigns on breast cancer predominantly focuses on female breast cancer due to its rarity in males. Treatment options for males are usually extrapolated from clinical trials conducted on females, as there are fewer clinical trials conducted solely on males; therefore, MBC does not currently have a standard of care. In addition, there is a dearth of large registry-based studies on the assessment of mortality trends among males. Therefore, using the Centre for Disease Control Wide-ranging Online Data for Epidemiologic Research (CDC-WONDER) Database, we sought to study the various mortality trends for MBC. The study aims to assess the mortality trends in elderly males by race/ethnicity, urbanization, state, and US census region. METHODOLOGY Data source : The analysis of the mortality trends in male adults with breast cancer (BC) across the USA from 1999 to 2020 was performed using data from the CDC WONDER (Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research) database [ 8 ]. The Multiple Cause-of-Death Public Use record death certificates were examined to discern whether BC was a contributing or underlying cause of death. Male breast cancer patients were identified using codes from the International Statistical Classification of Diseases 10th Revision Clinical Modification MCD - ICD-10 Codes: C50.0 to C50.9. Older adults were defined as those who were 65 years or older at the time of death. This study was exempt from local Institutional Review Board approval because the CDC WONDER database contains publicly available, and anonymized data. All methods employed in our study were conducted strictly per the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines [ 9 ]. All data collection, analysis, and interpretation were performed under our institution’s established ethical standards and protocols and in compliance with international research standards. Data extraction : MBC-related deaths, male population sizes, year, race/ethnicity, and regional information (urban-rural status, states, and regions of the United States) spanning from 1999–2020 were extracted from CDC WONDER. Race/ethnicities were defined as Hispanic or Latino, non-Hispanic White, non-Hispanic Black or African American, non-Hispanic American Indian or Alaskan Native, and non-Hispanic Asian or Pacific Islander patients. For urban-rural classifications, the 2013 National Center for Health Statistics Urban-Rural Classification Scheme was used to divide the counties into two categories: urban (comprising both large metropolitan areas with populations of 1 million or more, and medium/small metropolitan areas with populations between 250,000 and 999,999) and rural (with populations of less than 250,000). Regions were classified into Northeast, Midwest, South, and West according to the U.S. Census Bureau definitions. Statistical Analysis: The crude and age-adjusted mortality rates (AAMRs) per million population from 1999–2020 by year, race/ethnicity, state, urban-rural status, and region, along with 95% confidence intervals (CIs), were used to assess trends in male breast cancer-related mortality. The crude mortality rate was calculated by dividing the number of male breast cancer-related deaths by the corresponding U.S. population of that year. AAMRs were determined by standardizing male breast cancer-related deaths to the 2000 US population. The annual percent change (APC) with 95% CI in AAMR CI was determined using the Joinpoint Regression Program (Joinpoint V 5.0, National Cancer Institute). This allowed significant changes in AAMR for MBC to be determined by fitting long linear regression models within temporal variations. APCs were deemed to be either increasing or decreasing if the slope representing the change in mortality significantly differed from zero using 2-tailed t-testing. A p-value of < 0.05 was considered statistically significant. RESULTS Annual trends for MBC-related AAMR: Between 1999 and 2020, 8780 MBC-related deaths were reported. Throughout this period, AAMRs remained steady starting at 25.8 (95% CI: 23.0 to 28.6) in 1999, and decreasing to 23.0 (95% CI: 21.0 to 25.0) in 2020 ( Supplementary Table 1) .This marked an average annual percentage change (AAPC) of -1.29 (95% CI: -1.85 to -0.71). (Figure 1) MBC-related AAMR stratified by race: Although AAMRs decreased for both NH African American or Black and NH White patients from 1999 to 2020, NH Black patients had nearly twice the total AAMR compared to NH White patients (38.5 vs. 23.8) (Supplementary Table 2) . Furthermore, NH White patients experienced a significant decrease in mortality with an APC of 1.22% (95% CI: -1.76 to -0.65), which was double the APC observed in NH Black patients, 0.71% (95% CI: -2.06 to -0.88) (Figure 2) . The data for other races were suppressed or deemed unreliable. According to the CDC, the rates are marked as "unreliable" when the death count is less than 20. MBC-related AAMR stratified by urban-rural status: Mortality rates in both urban and rural areas displayed fluctuating trends from 1999 to 2020, with similar AAMRs (23.8 vs 22.7) (Supplementary Table 3 ). Notably, urban areas experienced a greater decrease in mortality rates per year by 2.6 folds (Figure 3) . MBC-related AAMR stratified by Region and State: Over the course of our study period, the highest AAMR was observed in the Northeast region (28.2) followed by the Midwest (25.3), South (22.4), and West (19.4) regions (Figure 4, Supplementary table 4) . When stratified by states, those in the top 90th percentile, including Rhode Island, New Jersey, Vermont, Maryland, and Georgia, had nearly double the AAMR compared to states in the lowest 10th percentile, namely California, Texas, Arizona, Utah, and Hawaii. (Supplementary Table 5) . Data for Alaska, the District of Columbia, North Dakota, and Wyoming were suppressed or deemed unreliable. (Figure 5) . DISCUSSION Male breast cancer (MBC) is rare and accounts for around 1% of all breast cancers globally, and 1% of malignancies that affect males [ 4 ]. Using the national death certificate from CDC WONDER, we observed that overall breast cancer mortality trends in men have shown improvement over the years. In our study, a total of 8780 elderly men died from breast cancer from 1999 to 2020. However, the mortality trends for males have remained higher than for females over the past years. Similar mortality trends for MBC are reported in other studies as well [ 10 ] [ 11 ]. Furthermore, in a large study conducted by Pizzato et al, no statistically significant change in specific mortality of MBC has been noted in the last 3 decades in the USA [ 12 ]. Lastly, another study observed, mortality dropped steadily between 2000 and 2017; however, the decline slowed significantly after 2002, decreasing from − 11.7% annually to -0.4% [ 13 ]. Mortality trends among males with breast cancer vary by race and ethnicity as well. Death rates are higher for non-Hispanic African American or Black males compared to non-Hispanic White males. This is also aligned with the CDC’s National Program of Cancer Registries data which documented similar findings that 1-year relative survival was increased with a percentage of about 96.4% among Whites, whereas it was 93.7% for African American [ 4 ]. Furthermore, the 2023 American Cancer Society (ACS) reported that Black patients have around 20% higher mortality than their White counterparts despite both developing the same cancer type [ 14 ]. Several reasons have been postulated for this racial disparity which stems not only from genetics reasons but from socioeconomic factors between races as well [ 15 ] [ 16 ]. This is further proved in a large cohort study by Parise et al, who concluded that black men have higher rates of mortality as compared to the White population, and this disparity is influenced by various demographic and clinical factors [ 17 ]. Although our study does not provide us with data on mortalities caused by tumor subtypes, previous studies have documented survival differences according to it. The overall survival for triple receptor-negative breast cancer in males is strikingly low. When compared with females, males have 4.3 times higher mortality for triple receptor-negative breast cancer [ 18 , 19 ]. Furthermore, non-Hispanic Blacks are more likely to develop triple receptor-negative and estrogen receptor-positive disease tumors than White men [ 14 ]. The health care disparity between White and Black populations in the United States is well documented in various studies, including the fact that more participation of Whites is seen in clinical trials as compared to Blacks [ 20 , 21 ]. Socioeconomic factors, financial burdens, and biases among races also have led to higher mortality in Blacks as compared to their White counterparts [ 22 , 23 ]. The graphs of urban and rural mortality rates overlap and cross, making it difficult to determine definitive differences. Nevertheless, rural areas still experience substantially higher healthcare needs, awareness issues, late diagnosis, and late treatment, and are often at a disadvantage in terms of access to healthcare services and proximity to screening facilities [ 24 , 25 ]. Furthermore, risk factors, such as obesity and smoking are more prevalent in rural communities. This could result in higher incidence and mortality rates due to cancers [ 26 , 27 ], and studies have also identified obesity as a potential cause of breast cancer [ 28 , 29 ]. Among postmenopausal females, substantial evidence indicates that a higher body mass index and increased central adiposity are linked to a greater risk of developing breast tumors, particularly in those with an existing familial risk [ 30 ]. In a study by Swerdlow et al., the relationships between BMI, central obesity, and male breast cancer at different ages were investigated. He concluded that central obesity is associated with an increased risk of MBC, especially for individuals with HER2-positive tumors [ 31 ]. Our study also observed that Rhode Island and the Northeast region of the USA have the highest mortality rates among the elderly. While 1-year survival rates for male breast cancer showed minimal variation across all age groups and U.S. regions, 5-year survival estimates differed slightly. Nationally, 1-year survival ranged from 95.6% (Midwest) to 97.4% (West). However, the gap between regions widened for 5-year survival, with the West again at the highest (87.0%) and the Midwest at the lowest (82.7%) [ 32 ]. In a review by Rees et al for various types of cancers, he reported that while the northeast region boasts lower overall cancer mortality rates compared to the national average, a unique trend emerges in the tri-state area of Maine, New Hampshire, and Vermont. Here, various cancer incidence rates tend to be higher than the US average [ 33 ]. Management of older male patients with breast cancer not only depends on the disease itself but is also complicated by comorbidities, drug tolerance, and physical condition, along with the scarcity of male representation in clinical trials represents an additional challenge [ 34 – 36 ]. The retrospective joint analyses and prospective registry components of the International Male Breast Cancer Program (IMBCP) have also found that male breast cancer patients receive lower quality of care compared to female patients [ 37 ]. There are a few limitations in our study. The data reported rely on ICD codes and death certificates, so misclassification could be present. Furthemore, baseline tumor characteristics could not be ascertained. Lastly, data regarding socioeconomic determinants of health were also not available, which may affect access to care. CONCLUSION In conclusion, despite improvements in mortality rates for males with breast cancer in the last two decades, they remain higher as compared to females. This could be due to less awareness and screening of males for breast cancer as compared to females. Highest AAMRs were observed among non-Hispanic Blacks or African Americans, in urban areas, the Northeast region, and in the state of Rhode Island, United States, in our study of elderly males aged ≥ 65 years. Further efforts and research are needed to reduce preventable deaths by ensuring equitable care. Declarations ACKNOWLEDGMENTS None. Funding Statement This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Author Contributions: .Rawdah Shakil: Conceptualization, Data curation, Supervision, Visualization, Writing – original draft, Writing – review & editing. Sabin Zafar: Conceptualization, Formal Analysis, Project administration, Visualization, Writing – original draft, Writing – review & editing, Supervision. Momina Javed: Visualization, Writing – original draft, Writing – review and editing, methodology Shahzaib Khan: Writing – original draft, Writing – review and editing, Supervision. Fatima Najam: Methodology, Writing – original draft. Marium Shahabi: Writing – original draft, Writing – review and editing, Visualization. Minahil Rehan: Writing original draft, conceptualization Abdullah Akram: writing original draft, extraction Amna Rizwan: extraction, methodology Syed Mohamin Abbas Shah: Reviewing, Supervision Data Availability: The data collected for this study could be available in a de-identified form after a reasonable request. Ethics Approval And Consent To Participate : This study was conducted using publicly available data from the CDC WONDER database, which is de-identified and aggregated to protect individual privacy. As a result, this research did not require formal ethical approval or individual consent to participate. 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Characterization of male breast cancer: results of the EORTC 10085/TBCRC/BIG/NABCG International Male Breast Cancer Program. Annals of Oncology 2018;29:405–17. https://doi.org/10.1093/annonc/mdx651. Additional Declarations No competing interests reported. Supplementary Files FINALTABLES1.docx MBCGraphicalAbstractpagestojpg0001.jpg Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7040692","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":491470843,"identity":"80c77dad-be50-4daa-80aa-22a1fb5ecc3e","order_by":0,"name":"Rawdah Shakil","email":"","orcid":"","institution":"Dow International Medical College","correspondingAuthor":false,"prefix":"","firstName":"Rawdah","middleName":"","lastName":"Shakil","suffix":""},{"id":491470844,"identity":"a315912d-716d-4d9a-a419-dd2afcce5e1f","order_by":1,"name":"Sabin Zafar","email":"","orcid":"","institution":"Jinnah Sindh Medical 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Shah","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA+0lEQVRIiWNgGAWjYFACHiA2ACIJIP3hAERMAiJGhBbGGcRrYYBoYeYhRotue+/BTzcK7sibSzc//mxzxiba4ADzwds8DHeMcWkxO3MuWTrH4JnhzjnHzKRzbqTlbjjAlmzNw/DMDKeWGzkGQC2HGTfcSDBjzvlwGKiFx0yah+GwDR4txr+BWuw33Ej//Nniw3+gFv5vhLSYgWxJ3ACyjuHGAZAtbCAtuB125oyZNVBL8s45Z8oke84k5848zGZsOcfgGW7vH+8xvp3z57Dtdun2zR9+HLPL7Tve/PDGm4o7hg249GACZhBhcIB4DTBAhpZRMApGwSgYrgAA5YNhgnFzWl4AAAAASUVORK5CYII=","orcid":"","institution":"King Edward Medical University","correspondingAuthor":true,"prefix":"","firstName":"Syed","middleName":"Mohamin Abbas","lastName":"Shah","suffix":""}],"badges":[],"createdAt":"2025-07-03 18:08:16","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7040692/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7040692/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":87832490,"identity":"02870898-0444-4f88-9140-9e7b62e591a4","added_by":"auto","created_at":"2025-07-29 12:40:05","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":29922,"visible":true,"origin":"","legend":"\u003cp\u003eOverall MBC–Related AAMRs per million in the United States, 1999 to 2020\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e∗\u003c/strong\u003eIndicates that the APC is significantly different from zero at α = 0.05.\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-7040692/v1/75e795703444322a93da23a8.png"},{"id":87832492,"identity":"70007d34-3797-4a65-85ba-4fd8c871c9a4","added_by":"auto","created_at":"2025-07-29 12:40:05","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":29792,"visible":true,"origin":"","legend":"\u003cp\u003eMBC–Related AAMRs per million Stratified by Race United States, 1999 to 2020\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e∗\u003c/strong\u003eIndicates that the APC is significantly different from zero at α = 0.05. NH = non-Hispanic.\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-7040692/v1/4e646e228c34e495d87b0c62.png"},{"id":87832493,"identity":"518c805b-00e0-44cb-ae9e-bc82a8bcae8f","added_by":"auto","created_at":"2025-07-29 12:40:05","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":45535,"visible":true,"origin":"","legend":"\u003cp\u003eMBC–Related AAMRs per million Stratified by Urban-Rural Status in the United States, 1999 to 2020\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-7040692/v1/297209e4f50e124797e1b807.png"},{"id":87832495,"identity":"d6729de6-329f-461a-a6d6-0785702e21cc","added_by":"auto","created_at":"2025-07-29 12:40:05","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":76938,"visible":true,"origin":"","legend":"\u003cp\u003eMBC–Related AAMRs per million Stratified by Region in the United States, 1999 to 2020\u003c/p\u003e","description":"","filename":"floatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-7040692/v1/07988e74536977456f7a3581.png"},{"id":87832500,"identity":"9f35548a-f263-41fc-855b-2d84017551ad","added_by":"auto","created_at":"2025-07-29 12:40:05","extension":"jpeg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":69600,"visible":true,"origin":"","legend":"\u003cp\u003eMBC–Related AAMRs per million Stratified by State in the United States, 1999 to 2020\u003c/p\u003e","description":"","filename":"floatimage5.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7040692/v1/a5a9e665d8881c1afd790d7c.jpeg"},{"id":93432825,"identity":"eb2fbe80-8ab6-4017-870b-0ee15297d14c","added_by":"auto","created_at":"2025-10-13 18:46:35","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":824341,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7040692/v1/a004a4d7-a571-4f37-a85d-5672042f2f97.pdf"},{"id":87833021,"identity":"8408c7cc-5bf4-4406-baee-7bbfa54d2863","added_by":"auto","created_at":"2025-07-29 12:48:05","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":38078,"visible":true,"origin":"","legend":"","description":"","filename":"FINALTABLES1.docx","url":"https://assets-eu.researchsquare.com/files/rs-7040692/v1/5c4bba5f93be3df982cb1056.docx"},{"id":87832496,"identity":"8946fece-a1a2-4264-b203-a96178107ae3","added_by":"auto","created_at":"2025-07-29 12:40:05","extension":"jpg","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":5244915,"visible":true,"origin":"","legend":"","description":"","filename":"MBCGraphicalAbstractpagestojpg0001.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7040692/v1/3ea1740742126c1cf415de20.jpg"}],"financialInterests":"No competing interests reported.","formattedTitle":"Trends in Breast Cancer Mortality Among Elderly Males in the United States (1999–2020): A CDC WONDER Analysis","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eMale breast cancer (MBC) typically presents with nipple retraction or painless subareolar masses [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. The risk factors include family history, hormonal imbalances such as an excess of estrogen and low production of androgens, alcohol consumption, and radiation exposure. Family history is usually linked to genetic mutations in the high-penetrance genes, BRCA1 and BRCA2 [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Individuals with BRCA2 mutations have an estimated 6.9% lifetime risk of developing breast cancer, which is approximately 80 to 100 times higher than the general population [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. In addition, the majority of tumors among men are estrogen receptor-positive [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eIn the USA, about 1 out of every 100 breast cancers diagnosed in the United States is found in a man and it is estimated that approximately 2,300 new cases and 500 associated deaths were reported in 2017, accounting for approximately 1% of all breast cancers [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. The incidence of invasive breast cancer in men is 1.28 per 100,000 and increases with age. Those aged 80 years and over (the elderly) have an incidence of about 8.30, with a mortality rate of 2.68 per 100,000 men[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Furthermore, the 5- and 10-year unadjusted survival rates for MBC were 77.7% and 60.7%, respectively, from 2004 to 2015 based on data from the National Cancer Database [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eAdditionally, older males have advanced and aggressive cancer features such as a higher frequency of metastatic spread to lymph nodes, higher rates of stage III and IV disease, and larger sizes of tumors [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. However, there is a delay in the presentation which is due to the lack of awareness and absence of targeted screening mammograms for men which leads to the development of widespread advanced disease and higher mortality as compared to females [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe development of novel treatment options, clinical trials, literature, and awareness campaigns on breast cancer predominantly focuses on female breast cancer due to its rarity in males. Treatment options for males are usually extrapolated from clinical trials conducted on females, as there are fewer clinical trials conducted solely on males; therefore, MBC does not currently have a standard of care. In addition, there is a dearth of large registry-based studies on the assessment of mortality trends among males. Therefore, using the Centre for Disease Control Wide-ranging Online Data for Epidemiologic Research (CDC-WONDER) Database, we sought to study the various mortality trends for MBC. The study aims to assess the mortality trends in elderly males by race/ethnicity, urbanization, state, and US census region.\u003c/p\u003e"},{"header":"METHODOLOGY","content":"\u003cp\u003e\u003cb\u003eData source\u003c/b\u003e:\u003c/p\u003e\u003cp\u003eThe analysis of the mortality trends in male adults with breast cancer (BC) across the USA from 1999 to 2020 was performed using data from the CDC WONDER (Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research) database [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. The Multiple Cause-of-Death Public Use record death certificates were examined to discern whether BC was a contributing or underlying cause of death. Male breast cancer patients were identified using codes from the International Statistical Classification of Diseases 10th Revision Clinical Modification MCD - ICD-10 Codes: C50.0 to C50.9. Older adults were defined as those who were 65 years or older at the time of death. This study was exempt from local Institutional Review Board approval because the CDC WONDER database contains publicly available, and anonymized data. All methods employed in our study were conducted strictly per the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. All data collection, analysis, and interpretation were performed under our institution’s established ethical standards and protocols and in compliance with international research standards.\u003c/p\u003e\u003cp\u003e\u003cb\u003eData extraction\u003c/b\u003e:\u003c/p\u003e\u003cp\u003eMBC-related deaths, male population sizes, year, race/ethnicity, and regional information (urban-rural status, states, and regions of the United States) spanning from 1999–2020 were extracted from CDC WONDER. Race/ethnicities were defined as Hispanic or Latino, non-Hispanic White, non-Hispanic Black or African American, non-Hispanic American Indian or Alaskan Native, and non-Hispanic Asian or Pacific Islander patients. For urban-rural classifications, the 2013 National Center for Health Statistics Urban-Rural Classification Scheme was used to divide the counties into two categories: urban (comprising both large metropolitan areas with populations of 1\u0026nbsp;million or more, and medium/small metropolitan areas with populations between 250,000 and 999,999) and rural (with populations of less than 250,000). Regions were classified into Northeast, Midwest, South, and West according to the U.S. Census Bureau definitions.\u003c/p\u003e\u003ch2\u003eStatistical Analysis:\u003c/h2\u003e\u003cp\u003eThe crude and age-adjusted mortality rates (AAMRs) per million population from 1999–2020 by year, race/ethnicity, state, urban-rural status, and region, along with 95% confidence intervals (CIs), were used to assess trends in male breast cancer-related mortality. The crude mortality rate was calculated by dividing the number of male breast cancer-related deaths by the corresponding U.S. population of that year. AAMRs were determined by standardizing male breast cancer-related deaths to the 2000 US population. The annual percent change (APC) with 95% CI in AAMR CI was determined using the Joinpoint Regression Program (Joinpoint V 5.0, National Cancer Institute). This allowed significant changes in AAMR for MBC to be determined by fitting long linear regression models within temporal variations. APCs were deemed to be either increasing or decreasing if the slope representing the change in mortality significantly differed from zero using 2-tailed t-testing. A p-value of \u0026lt; 0.05 was considered statistically significant.\u003c/p\u003e"},{"header":"RESULTS","content":"\u003ch3\u003e\u003cstrong\u003eAnnual trends for MBC-related AAMR:\u003c/strong\u003e\u003c/h3\u003e\n\u003cp\u003eBetween 1999 and 2020, 8780 MBC-related deaths were reported. Throughout this period, AAMRs remained steady starting at 25.8 (95% CI: 23.0 to 28.6) in 1999, and decreasing to 23.0 (95% CI: 21.0 to 25.0) in 2020 (\u003cstrong\u003eSupplementary Table 1)\u003c/strong\u003e.This marked an average annual percentage change (AAPC) of -1.29 (95% CI: -1.85 to -0.71). \u003cstrong\u003e(Figure 1)\u003c/strong\u003e\u003c/p\u003e\n\u003ch3\u003e\u003cstrong\u003eMBC-related AAMR stratified by race:\u003c/strong\u003e\u003c/h3\u003e\n\u003cp\u003eAlthough AAMRs decreased for both NH African American or Black and NH White patients from 1999 to 2020, NH Black patients had nearly twice the total AAMR compared to NH White patients (38.5 vs. 23.8) \u003cstrong\u003e(Supplementary Table 2)\u003c/strong\u003e. Furthermore, NH White patients experienced a significant decrease in mortality with an APC of 1.22% (95% CI: -1.76 to -0.65), which was double the APC observed in NH Black patients, 0.71% (95% CI: -2.06 to -0.88)\u003cstrong\u003e\u0026nbsp;(Figure 2)\u003c/strong\u003e.\u003c/p\u003e\n\u003cp\u003eThe data for other races were suppressed or deemed unreliable. According to the CDC, the rates are marked as \u0026quot;unreliable\u0026quot; when the death count is less than 20.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMBC-related AAMR stratified by urban-rural status:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMortality rates in both urban and rural areas displayed fluctuating trends from 1999 to 2020, with similar AAMRs (23.8 vs 22.7) \u003cstrong\u003e(Supplementary Table 3\u003c/strong\u003e). Notably, urban areas experienced a greater decrease in mortality rates per year by 2.6 folds \u003cstrong\u003e(Figure 3)\u003c/strong\u003e.\u003c/p\u003e\n\u003ch3\u003e\u003cstrong\u003eMBC-related AAMR stratified by Region and State:\u003c/strong\u003e\u003c/h3\u003e\n\u003cp\u003eOver the course of our study period, the highest AAMR was observed in the Northeast region (28.2) followed by the Midwest (25.3), South (22.4), and West (19.4) regions \u003cstrong\u003e(Figure 4, Supplementary table 4)\u003c/strong\u003e.\u003c/p\u003e\n\u003cp\u003eWhen stratified by states, those in the top 90th percentile, including Rhode Island, New Jersey, Vermont, Maryland, and Georgia, had nearly double the AAMR compared to states in the lowest 10th percentile, namely California, Texas, Arizona, Utah, and Hawaii.\u003cstrong\u003e\u0026nbsp;(Supplementary Table 5)\u003c/strong\u003e.\u003c/p\u003e\n\u003cp\u003eData for Alaska, the District of Columbia, North Dakota, and Wyoming were suppressed or deemed unreliable. \u003cstrong\u003e(Figure 5)\u003c/strong\u003e.\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eMale breast cancer (MBC) is rare and accounts for around 1% of all breast cancers globally, and 1% of malignancies that affect males [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Using the national death certificate from CDC WONDER, we observed that overall breast cancer mortality trends in men have shown improvement over the years. In our study, a total of 8780 elderly men died from breast cancer from 1999 to 2020. However, the mortality trends for males have remained higher than for females over the past years. Similar mortality trends for MBC are reported in other studies as well [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e] [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Furthermore, in a large study conducted by Pizzato et al, no statistically significant change in specific mortality of MBC has been noted in the last 3 decades in the USA [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Lastly, another study observed, mortality dropped steadily between 2000 and 2017; however, the decline slowed significantly after 2002, decreasing from \u0026minus;\u0026thinsp;11.7% annually to -0.4% [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eMortality trends among males with breast cancer vary by race and ethnicity as well. Death rates are higher for non-Hispanic African American or Black males compared to non-Hispanic White males. This is also aligned with the CDC\u0026rsquo;s National Program of Cancer Registries data which documented similar findings that 1-year relative survival was increased with a percentage of about 96.4% among Whites, whereas it was 93.7% for African American [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Furthermore, the 2023 American Cancer Society (ACS) reported that Black patients have around 20% higher mortality than their White counterparts despite both developing the same cancer type [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Several reasons have been postulated for this racial disparity which stems not only from genetics reasons but from socioeconomic factors between races as well [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e] [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. This is further proved in a large cohort study by Parise et al, who concluded that black men have higher rates of mortality as compared to the White population, and this disparity is influenced by various demographic and clinical factors [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eAlthough our study does not provide us with data on mortalities caused by tumor subtypes, previous studies have documented survival differences according to it. The overall survival for triple receptor-negative breast cancer in males is strikingly low. When compared with females, males have 4.3 times higher mortality for triple receptor-negative breast cancer [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Furthermore, non-Hispanic Blacks are more likely to develop triple receptor-negative and estrogen receptor-positive disease tumors than White men [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. The health care disparity between White and Black populations in the United States is well documented in various studies, including the fact that more participation of Whites is seen in clinical trials as compared to Blacks [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Socioeconomic factors, financial burdens, and biases among races also have led to higher mortality in Blacks as compared to their White counterparts [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe graphs of urban and rural mortality rates overlap and cross, making it difficult to determine definitive differences. Nevertheless, rural areas still experience substantially higher healthcare needs, awareness issues, late diagnosis, and late treatment, and are often at a disadvantage in terms of access to healthcare services and proximity to screening facilities [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. Furthermore, risk factors, such as obesity and smoking are more prevalent in rural communities. This could result in higher incidence and mortality rates due to cancers [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e], and studies have also identified obesity as a potential cause of breast cancer [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. Among postmenopausal females, substantial evidence indicates that a higher body mass index and increased central adiposity are linked to a greater risk of developing breast tumors, particularly in those with an existing familial risk [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. In a study by Swerdlow et al., the relationships between BMI, central obesity, and male breast cancer at different ages were investigated. He concluded that central obesity is associated with an increased risk of MBC, especially for individuals with HER2-positive tumors [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eOur study also observed that Rhode Island and the Northeast region of the USA have the highest mortality rates among the elderly. While 1-year survival rates for male breast cancer showed minimal variation across all age groups and U.S. regions, 5-year survival estimates differed slightly. Nationally, 1-year survival ranged from 95.6% (Midwest) to 97.4% (West). However, the gap between regions widened for 5-year survival, with the West again at the highest (87.0%) and the Midwest at the lowest (82.7%) [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. In a review by Rees et al for various types of cancers, he reported that while the northeast region boasts lower overall cancer mortality rates compared to the national average, a unique trend emerges in the tri-state area of Maine, New Hampshire, and Vermont. Here, various cancer incidence rates tend to be higher than the US average [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eManagement of older male patients with breast cancer not only depends on the disease itself but is also complicated by comorbidities, drug tolerance, and physical condition, along with the scarcity of male representation in clinical trials represents an additional challenge [\u003cspan additionalcitationids=\"CR35\" citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. The retrospective joint analyses and prospective registry components of the International Male Breast Cancer Program (IMBCP) have also found that male breast cancer patients receive lower quality of care compared to female patients [\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThere are a few limitations in our study. The data reported rely on ICD codes and death certificates, so misclassification could be present. Furthemore, baseline tumor characteristics could not be ascertained. Lastly, data regarding socioeconomic determinants of health were also not available, which may affect access to care.\u003c/p\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003eIn conclusion, despite improvements in mortality rates for males with breast cancer in the last two decades, they remain higher as compared to females. This could be due to less awareness and screening of males for breast cancer as compared to females. Highest AAMRs were observed among non-Hispanic Blacks or African Americans, in urban areas, the Northeast region, and in the state of Rhode Island, United States, in our study of elderly males aged\u0026thinsp;\u0026ge;\u0026thinsp;65 years. Further efforts and research are needed to reduce preventable deaths by ensuring equitable care.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eACKNOWLEDGMENTS\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interests:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e.Rawdah Shakil: Conceptualization, Data curation, Supervision, Visualization, Writing \u0026ndash; original draft, Writing \u0026ndash; review \u0026amp; editing.\u003c/p\u003e\n\u003cp\u003eSabin Zafar: Conceptualization, Formal Analysis, Project administration, Visualization, Writing \u0026ndash; original draft, Writing \u0026ndash; review \u0026amp; editing, Supervision.\u003c/p\u003e\n\u003cp\u003eMomina Javed: Visualization, Writing \u0026ndash; original draft, Writing \u0026ndash; review and editing, methodology\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eShahzaib Khan: Writing \u0026ndash; original draft, Writing \u0026ndash; review and editing, Supervision.\u003c/p\u003e\n\u003cp\u003eFatima Najam: Methodology, Writing \u0026ndash; original draft.\u003c/p\u003e\n\u003cp\u003eMarium Shahabi: Writing \u0026ndash; original draft, Writing \u0026ndash; review and editing, Visualization.\u003c/p\u003e\n\u003cp\u003eMinahil Rehan: Writing original draft, conceptualization\u003c/p\u003e\n\u003cp\u003eAbdullah Akram: writing original draft, extraction\u003c/p\u003e\n\u003cp\u003eAmna Rizwan: extraction,\u0026nbsp;methodology\u003c/p\u003e\n\u003cp\u003eSyed Mohamin Abbas Shah: Reviewing, Supervision\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data collected for this study could be available in a de-identified form after a reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics Approval And Consent To Participate\u003c/strong\u003e\u003cstrong\u003e:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was conducted using publicly available data from the CDC WONDER database, which is de-identified and aggregated to protect individual privacy. As a result, this research did not require formal ethical approval or individual consent to participate. The use of this data complies with ethical standards for research using secondary data sources.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to participate:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to publish:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eHasbay B, Bolat FA, Aytac HO, Kus M, Pourbagher A. Male breast cancer: clinicopathological, immunohistochemical and radiological study. Turkish Journal of Pathology 2020. https://doi.org/10.5146/tjpath.2020.01490.\u003c/li\u003e\n\u003cli\u003eFord D, Easton DF, Stratton M, Narod S, Goldgar D, Devilee P, et al. Genetic Heterogeneity and Penetrance Analysis of the BRCA1 and BRCA2 Genes in Breast Cancer Families. 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Disparity of Race Reporting and Representation in Clinical Trials Leading to Cancer Drug Approvals From 2008 to 2018. JAMA Oncol 2019;5:e191870. https://doi.org/10.1001/jamaoncol.2019.1870.\u003c/li\u003e\n\u003cli\u003eParekh T, Desai A. Demographic and Socioeconomic Disparities Among Cancer Survivors in Clinical Trials Participation, USA, 2016\u0026ndash;2018. Journal of Cancer Education 2022;37:88\u0026ndash;90. https://doi.org/10.1007/s13187-020-01790-6.\u003c/li\u003e\n\u003cli\u003eMaingi S, Dizon DS. Disparities in cancer care: A long way to go. CA Cancer J Clin 2024;74:133\u0026ndash;5. https://doi.org/10.3322/caac.21822.\u003c/li\u003e\n\u003cli\u003eObeng-Gyasi S. Advancing healthcare disparities research in patients with stage IV cancer. The American Journal of Surgery 2023;226:19. https://doi.org/10.1016/j.amjsurg.2023.04.012.\u003c/li\u003e\n\u003cli\u003eMoss JL, Ehrenkranz R, Perez LG, Hair BY, Julian AK. Geographic disparities in cancer screening and fatalism among a nationally representative sample of US adults. J Epidemiol Community Health (1978) 2019;73:1128\u0026ndash;35. https://doi.org/10.1136/jech-2019-212425.\u003c/li\u003e\n\u003cli\u003eAruma J-F, Hearn M, Bernacchi V, Moss JL. Examining the roles of travel distance, medical mistrust, and cancer fatalism in the uptake of clinical cancer prevention among women in rural and urban US communities: A secondary data analysis. Prev Med Rep 2024;38:102611. https://doi.org/10.1016/j.pmedr.2024.102611.\u003c/li\u003e\n\u003cli\u003eSteele CB, Thomas CC, Henley SJ, Massetti GM, Galuska DA, Agurs-Collins T, et al. \u003cem\u003eVital Signs\u003c/em\u003e : Trends in Incidence of Cancers Associated with Overweight and Obesity \u0026mdash; United States, 2005\u0026ndash;2014. MMWR Morb Mortal Wkly Rep 2017;66:1052\u0026ndash;8. https://doi.org/10.15585/mmwr.mm6639e1.\u003c/li\u003e\n\u003cli\u003eWang K, Li F, Zhang X, Li Z, Li H. 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Cancer Research Communications 2023;3:1538\u0026ndash;50. https://doi.org/10.1158/2767-9764.CRC-23-0152.\u003c/li\u003e\n\u003cli\u003eBiganzoli L, Battisti NML, Wildiers H, McCartney A, Colloca G, Kunkler IH, et al. Updated recommendations regarding the management of older patients with breast cancer: a joint paper from the European Society of Breast Cancer Specialists (EUSOMA) and the International Society of Geriatric Oncology (SIOG). Lancet Oncol 2021;22:e327\u0026ndash;40. https://doi.org/10.1016/S1470-2045(20)30741-5.\u003c/li\u003e\n\u003cli\u003eEdwards BK, Noone A, Mariotto AB, Simard EP, Boscoe FP, Henley SJ, et al. Annual Report to the Nation on the status of cancer, 1975‐2010, featuring prevalence of comorbidity and impact on survival among persons with lung, colorectal, breast, or prostate cancer. Cancer 2014;120:1290\u0026ndash;314. https://doi.org/10.1002/cncr.28509.\u003c/li\u003e\n\u003cli\u003eEl Fouhi M, Mesfioui A, Benider A. Male breast cancer: a report of 25 cases. Pan African Medical Journal 2020;37. https://doi.org/10.11604/pamj.2020.37.343.23004.\u003c/li\u003e\n\u003cli\u003eCardoso F, Bartlett JMS, Slaets L, van Deurzen CHM, van Leeuwen-Stok E, Porter P, et al. Characterization of male breast cancer: results of the EORTC 10085/TBCRC/BIG/NABCG International Male Breast Cancer Program. Annals of Oncology 2018;29:405\u0026ndash;17. https://doi.org/10.1093/annonc/mdx651.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"CDC Wonder, Male breast cancer, Mortality","lastPublishedDoi":"10.21203/rs.3.rs-7040692/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7040692/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003ePurpose: \u003c/strong\u003eWhile male breast cancer (MBC) is rare, existing studies often exclude elderly males or lack detailed analysis by demographic and geographic factors. Our purpose was to evaluate mortality trends in elderly males (≥65 years) with breast cancer from 1999–2020 by various demographics\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethodology:\u003c/strong\u003e Death certificate data (1999-2020) from the CDC WONDER database were examined for MBC-related mortality in males aged ≥65 years using ICD-10 codes, C50.0 to C50.9. Age-adjusted mortality rates (AAMR) per million persons (95% CIs) were calculated, and the Joinpoint Regression model was used to calculate the annual percentage change (APC).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e The overall APC was -1.29 (95% CI: -1.85 to -0.71), and a total of 8780 deaths from 1999 to 2020 were reported. The AAMR decreased from 25.0 in 1999 to 23.0 in 2020 for non-Hispanic White elderly males, marking a significant drop of 1.22% (95% CI:-1.76 to -0.65)in mortality per year. In contrast, annual mortality among non-Hispanic Black or African American patients showed a non-significant decrease of 0.71% (95% CI: -2.06 to -0.88). Geographically, the highest total AAMRs were observed in rural areas, the Northeast region, and Rhode Island, while the lowest in urban areas, the West, and Hawaii.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e Overall mortality has significantly dropped\u003cstrong\u003e \u003c/strong\u003eover the last two decades. The disparity between the races may be attributed to various factors such as genetic differences and socioeconomic factors. These results highlight the need for further research into the observed disparities and for more screening, public awareness, and male-oriented clinical trials.\u003c/p\u003e","manuscriptTitle":"Trends in Breast Cancer Mortality Among Elderly Males in the United States (1999–2020): A CDC WONDER Analysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-07-29 12:40:00","doi":"10.21203/rs.3.rs-7040692/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"81206abb-e713-4768-b125-a2ce1018879d","owner":[],"postedDate":"July 29th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-10-13T18:38:25+00:00","versionOfRecord":[],"versionCreatedAt":"2025-07-29 12:40:00","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7040692","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7040692","identity":"rs-7040692","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}