Abstract
While it is well-established that cardiovascular disease and congestive heart failure (CHF) are increased among breast cancer survivors, little is known about how systemic therapy use, medical comorbidities, and socioeconomic factors interact to influence long-term cardiac outcomes. In this study, we performed an analysis of the SEER-Medicare database, including more than 200,000 patients with early-stage breast cancer. Using available zip code and census data, patient disease characteristics and cardiac outcomes were stratified by socioeconomic variables. Overall, patients of Black, Hispanic, and American Indian/Alaskan Native race/ethnicity had an increased incidence of large, high-grade tumors and nodal involvement as compared to White and Asian American/Pacific Islander (AAPI) patients. Lower per capita income (PCI), higher percentage of population living in poverty, lower level of education, and not speaking English at home were also associated with increased tumor size, grade, and nodal stage. Adjusting for cardiac covariates and cancer therapy type, a multivariate socioeconomic model revealed that Black patients had a higher risk of CHF and AAPI patients had a lower risk compared to White patients. Further adjusting for race/ethnicity, patients living in a zip code in the lowest quartile of PCI also had a higher risk of CHF compared to those in the highest quartile.
Data availability
This study used the linked SEER-Medicare database. The interpretation and reporting of these data are the sole responsibility of the authors.
Code availability
Not applicable.
References
Siegel, R. L., Giaquinto, A. N. & Jemal, A. Cancer statistics, 2024. CA Cancer J. Clin. 74, 12–49 (2024).
American Cancer Society. Breast Cancer Facts & Figures 2022–2024. Atlanta: American Cancer Society, Inc. (2022).
Slamon, D. J. et al. Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science 244, 707–712 (1989).
Patnaik, J. L., Byers, T., DiGuiseppi, C., Dabelea, D., & Denberg, T. D. Cardiovascular disease competes with breast cancer as the leading cause of death for older females diagnosed with breast cancer: a retrospective cohort study. Breast Cancer Res. 13, R64 (2011).
Greenlee, H. et al. Risk of cardiovascular disease in women with and without breast cancer: the pathways heart study. J. Clin. Oncol. 40, 1647–1658 (2022).
Sprague, B. L. et al. Socioeconomic status and survival after an invasive breast cancer diagnosis. Cancer 117, 1542–1551, https://doi.org/10.1002/cncr.25589 (2011).
Singh, G. K. & Jemal, A. Socioeconomic and racial/ethnic disparities in cancer mortality, incidence, and survival in the United States, 1950-2014: over six decades of changing patterns and widening inequalities. J. Environ. Public Health 2017, 2819372 (2017).
Coughlin, S. S. Social determinants of breast cancer risk, stage, and survival. Breast Cancer Res. Treat. 177, 537–548 (2019).
Kenzik, K. M., Rocque, G. B., Landier, W. & Bhatia, S. Urban versus rural residence and outcomes in older patients with breast cancer. Cancer Epidemiol. Biomark. Prev. 29, 1313–1320 (2020).
Williams, F. & Thompson, E. Disparities in breast cancer stage at diagnosis: importance of race, poverty, and age. J. Health Dispar. Res. Pract. 10, 34–45 (2017).
Moss, J. L., Pinto, C. N., Srinivasan, S., Cronin, K. A. & Croyle, R. T. Persistent poverty and cancer mortality rates: an analysis of county-level poverty designations. Cancer Epidemiol. Biomark. Prev. 29, 1949–1954 (2020).
Moss, J. L., Pinto, C. N., Srinivasan, S., Cronin, K. A. & Croyle, R. T. Enduring cancer disparities by persistent poverty, rurality, and race: 1990–1992 to 2014–2018. J. Natl. Cancer Inst. 114, 829–836 (2022).
Raisi-Estabragh, Z. et al. Incident cardiovascular events and imaging phenotypes in UK Biobank participants with past cancer. Heart 109, 1007–1015 (2023).
Chavez-MacGregor, M. et al. Trastuzumab-related cardiotoxicity among older patients with breast cancer. J. Clin. Oncol. 31, 4222–4228 (2013).
Von Hoff, D. D. et al. Risk factors for doxorubicin-induced congestive heart failure. Ann. Intern. Med. 91, 710–717 (1979).
Alexander, J. et al. Serial assessment of doxorubicin cardiotoxicity with quantitative radionuclide angiocardiography. N. Engl. J. Med 300, 278–283 (1979).
Buzdar, A. U., Marcus, C., Smith, T. L. & Blumenschein, G. R. Early and delayed clinical cardiotoxicity of doxorubicin. Cancer 55, 2761–2765 (1985).
Nicolazzi, M. A. et al. Anthracycline and trastuzumab-induced cardiotoxicity in breast cancer. Eur. Rev. Med. Pharm. Sci. 22, 2175–2185 (2018).
Gonciar, D., Mocan, L., Zlibut, A., Mocan, T. & Agoston-Coldea, L. Cardiotoxicity in HER2-positive breast cancer patients. Heart Fail Rev. 26, 919–935 (2021).
Ades, F. et al. Cardiotoxicity of systemic agents used in breast cancer. Breast 23, 317–328 (2014).
Domercant, J., Polin, N. & Jahangir, E. Cardio-oncology: a focused review of anthracycline-, human epidermal growth factor receptor 2 inhibitor-, and radiation-induced cardiotoxicity and management. Fall 16, 250–256 (2016).
Slamon, D. J. et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N. Engl. J. Med. 344, 783–792 (2001).
Stabellini, N. et al. Social determinants of health and racial disparities in cardiac events in breast cancer. J. Natl. Compr. Cancer Netw. 21, 705–714.e17 (2023).
Zhu, C. et al. Racial and ethnic disparities in all-cause and cardiovascular mortality among cancer patients in the U.S. JACC CardioOncol. 5, 55–66 (2023).
Troeschel, A. N. et al. Race differences in cardiovascular disease and breast cancer mortality among US women diagnosed with invasive breast cancer. Int. J. Epidemiol. 48, 1897–1905 (2019).
McAndrew, N. P. et al. Abstract P3-03-13: long-term heart failure risk of trastuzumab with or without anthracyclines in early stage breast cancer: a SEER-medicare database analysis. Cancer Res. 83, P3-03-13–P3-03-13 (2023).
Stead, L. A. et al. Triple-negative breast cancers are increased in black women regardless of age or body mass index. Breast Cancer Res. 11, R18 (2009).
Clegg, L. X., Li, F. P., Hankey, B. F., Chu, K. & Edwards, B. K. Cancer survival among US whites and minorities: a SEER (Surveillance, Epidemiology, and End Results) Program population-based study. Arch. Intern. Med. 162, 1985–1993 (2002).
Li, C. I., Malone, K. E. & Daling, J. R. Differences in breast cancer stage, treatment, and survival by race and ethnicity. Arch. Intern. Med. 163, 49–56 (2003).
Osei-Twum, J. A., Gedleh, S., Lofters, A. & Nnorom, O. Differences in breast cancer presentation at time of diagnosis for black and white women in high resource settings. J. Immigr. Minor Health 23, 1305–1342 (2021).
Danforth, D. N. Disparities in breast cancer outcomes between Caucasian and African American women: a model for describing the relationship of biological and nonbiological factors. Breast Cancer Res. 15, 208 (2013).
Joslyn, S. A. & West, M. M. Racial differences in breast carcinoma survival. Cancer 88, 114–123 (2000).
Newman, L. A. et al. African-American ethnicity, socioeconomic status, and breast cancer survival: a meta-analysis of 14 studies involving over 10,000 African-American and 40,000 White American patients with carcinoma of the breast. Cancer 94, 2844–2854 (2002).
Ward, E. et al. Cancer disparities by race/ethnicity and socioeconomic status. CA Cancer J. Clin. 54, 78–93 (2004).
Henry, K. A. et al. The joint effects of census tract poverty and geographic access on late-stage breast cancer diagnosis in 10 US States. Health Place 21, 110–121 (2013).
Nguyen-Pham, S., Leung, J. & McLaughlin, D. Disparities in breast cancer stage at diagnosis in urban and rural adult women: a systematic review and meta-analysis. Ann. Epidemiol. 24, 228–235 (2014).
Byers, T. E. et al. The impact of socioeconomic status on survival after cancer in the United States: findings from the National Program of Cancer Registries Patterns of Care Study. Cancer 113, 582–591 (2008).
Lund, M. J. et al. Race and triple negative threats to breast cancer survival: a population-based study in Atlanta, GA. Breast Cancer Res. Treat. 113, 357–370 (2009).
Zavala, V. A. et al. Cancer health disparities in racial/ethnic minorities in the United States. Br. J. Cancer 124, 315–332 (2021).
Ownby, H. E. et al. Racial differences in breast cancer patients. J. Natl. Cancer Inst. 75, 55–60 (1985).
Wang, L. H., Wu, C. F., Rajasekaran, N. & Shin, Y. K. Loss of tumor suppressor gene function in human cancer: an overview. Cell Physiol. Biochem. 51, 2647–2693 (2018).
D’Arcy, M. et al. Race-associated biological differences among Luminal A breast tumors. Breast Cancer Res. Treat. 152, 437–448 (2015).
Conway, K. et al. Racial variation in breast tumor promoter methylation in the Carolina Breast Cancer Study. Cancer Epidemiol. Biomark. Prev. 24, 921–930 (2015).
Mehrotra, J. et al. Estrogen receptor/progesterone receptor-negative breast cancers of young African-American women have a higher frequency of methylation of multiple genes than those of Caucasian women. Clin. Cancer Res. 10, 2052–2057 (2004).
Pierce, B. L. et al. Elevated biomarkers of inflammation are associated with reduced survival among breast cancer patients. J. Clin. Oncol. 27, 3437–3444 (2009).
Deshmukh, S. K. et al. Resistin and interleukin-6 exhibit racially-disparate expression in breast cancer patients, display molecular association and promote growth and aggressiveness of tumor cells through STAT3 activation. Oncotarget 6, 11231–11241 (2015).
Huffman, M. D. et al. Lifetime risk for heart failure among white and black Americans: cardiovascular lifetime risk pooling project. J. Am. Coll. Cardiol. 61, 1510–1517 (2013).
Benjamin, E. J. et al. Heart disease and stroke statistics-2019 update: a report from the American Heart Association. Circulation 139, e56–e528 (2019).
Bahrami, H. et al. Differences in the incidence of congestive heart failure by ethnicity: the multi-ethnic study of atherosclerosis. Arch. Intern. Med. 168, 2138–2145 (2008).
Nayak, A., Hicks, A. J. & Morris, A. A. Understanding the complexity of heart failure risk and treatment in black patients. Circ. Heart Fail 13, e007264 (2020).
Kalogeropoulos, A. et al. Epidemiology of incident heart failure in a contemporary elderly cohort: the health, aging, and body composition study. Arch. Intern. Med. 169, 708–715 (2009).
Lotrionte, M. et al. Review and meta-analysis of incidence and clinical predictors of anthracycline cardiotoxicity. Am. J. Cardiol. 112, 1980–1984 (2013).
Zhang, M., Yang, H., Xu, C., Jin, F. & Zheng, A. Risk factors for anthracycline-induced cardiotoxicity in breast cancer treatment: a meta-analysis. Front. Oncol. 12, 899782 (2022).
Qiu, S. et al. Risk factors for anthracycline-induced cardiotoxicity. Front. Cardiovasc. Med. 8, 736854 (2021).
Pinder, M. C., Duan, Z., Goodwin, J. S., Hortobagyi, G. N. & Giordano, S. H. Congestive heart failure in older women treated with adjuvant anthracycline chemotherapy for breast cancer. J. Clin. Oncol. 25, 3808–3815 (2007).
Al-Sadawi, M. et al. Racial and socioeconomic disparities in cardiotoxicity among women with HER2-positive breast cancer. Am. J. Cardiol. 147, 116–121 (2021).
Sutton, A. L. et al. Racial disparities in treatment-related cardiovascular toxicities amongst women with breast cancer: a scoping review. J. Cancer Surviv. 17, 1596–1605 (2023).
Roy, S. et al. Major cardiovascular adverse events in older adults with early-stage triple-negative breast cancer treated with adjuvant taxane + anthracycline versus taxane-based chemotherapy regimens: a SEER-medicare study. Eur. J. Cancer 196, 113426 (2024).
Liu, Y., Nguyen, N. & Colditz, G. A. Links between alcohol consumption and breast cancer: a look at the evidence. Women’s. Health 11, 65–77 (2015).
Secretan, B. et al. A review of human carcinogens-Part E: tobacco, areca nut, alcohol, coal smoke, and salted fish. Lancet Oncol. 10, 1033–1034 (2009).
Zhang, S. M. et al. Alcohol consumption and breast cancer risk in the Women’s Health Study. Am. J. Epidemiol. 165, 667–676 (2007).
Chen, W. Y., Rosner, B., Hankinson, S. E., Colditz, G. A. & Willett, W. C. Moderate alcohol consumption during adult life, drinking patterns, and breast cancer risk. JAMA 306, 1884–1890 (2011).
Bagnardi, V. et al. Alcohol consumption and site-specific cancer risk: a comprehensive dose-response meta-analysis. Br. J. Cancer 112, 580–593 (2015).
Djoussé, L. & Gaziano, J. M. Alcohol consumption and heart failure: a systematic review. Curr. Atheroscler. Rep. 10, 117–120 (2008).
Andersson, C., Schou, M., Gustafsson, F. & Torp-Pedersen, C. Alcohol intake in patients with cardiomyopathy and heart failure: consensus and controversy. Circ. Heart Fail 15, e009459 (2022).
Mozaffarian, D. et al. heart disease and stroke statistics-2016 update: a report from the American Heart Association. Circulation 133, e38–e360 (2016).
Lee, I. M. et al. Effect of physical inactivity on major non-communicable diseases worldwide: an analysis of burden of disease and life expectancy. Lancet 380, 219–229 (2012).
Zhou, Y., Zhao, H. & Peng, C. Association of sedentary behavior with the risk of breast cancer in women: update meta-analysis of observational studies. Ann. Epidemiol. 25, 687–697 (2015).
Katzmarzyk, P. T., Church, T. S., Craig, C. L. & Bouchard, C. Sitting time and mortality from all causes, cardiovascular disease, and cancer. Med. Sci. Sports Exerc. 41, 998–1005 (2009).
Friedenreich, C. M. Physical activity and breast cancer: review of the epidemiologic evidence and biologic mechanisms. Recent Results Cancer Res. 188, 125–139 (2011).
Lynch, B. M., Neilson, H. K. & Friedenreich, C. M. Physical activity and breast cancer prevention. Recent Results Cancer Res. 186, 13–42 (2011).
Cotterchio, M., Mirea, L., Ozcelik, H. & Kreiger, N. Active cigarette smoking, variants in carcinogen metabolism genes and breast cancer risk among pre- and postmenopausal women in Ontario, Canada. Breast J. 20, 468–480 (2014).
Xue, F., Willett, W. C., Rosner, B. A., Hankinson, S. E. & Michels, K. B. Cigarette smoking and the incidence of breast cancer. Arch. Intern Med. 171, 125–133 (2011).
Cui, Y., Miller, A. B. & Rohan, T. E. Cigarette smoking and breast cancer risk: update of a prospective cohort study. Breast Cancer Res. Treat. 100, 293–299 (2006).
U.S. Department of Health and Human Services. The health consequences of smoking—50 years of progress: a report of the surgeon general. (National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health, 2014).
Poirier, P. et al. Obesity and cardiovascular disease: pathophysiology, evaluation, and effect of weight loss: an update of the 1997 American Heart Association Scientific Statement on Obesity and Heart Disease from the Obesity Committee of the Council on Nutrition, Physical Activity, and Metabolism. Circulation 113, 898–918 (2006).
McTigue, K. M. et al. Severe obesity, heart disease, and death among white, African American, and Hispanic postmenopausal women. Obesity 22, 801–810 (2014).
Renehan, A. G., Tyson, M., Egger, M., Heller, R. F. & Zwahlen, M. Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies. Lancet 371, 569–578 (2008).
Kenchaiah, S. et al. Obesity and the risk of heart failure. N. Engl. J. Med. 347, 305–313 (2002).
Keum, N. et al. Adult weight gain and adiposity-related cancers: a dose-response meta-analysis of prospective observational studies. J. Natl. Cancer Inst. 107, djv088 (2015).
Berstad, P. et al. A case-control study of body mass index and breast cancer risk in white and African-American women. Cancer Epidemiol. Biomark. Prev. 19, 1532–1544 (2010).
Amadou, A. et al. Overweight, obesity and risk of premenopausal breast cancer according to ethnicity: a systematic review and dose-response meta-analysis. Obes. Rev. 14, 665–678 (2013).
Hales, C. M., Carroll, M. D., Fryar, C. D. & Ogden, C. L. Prevalence of obesity and severe obesity among adults: United States, 2017–2018. NCHS Data Brief. 1–8 (2020).
Zhao, G., Hsia, J., Vigo-Valentín, A., Garvin, W. S. & Town, M. Health-related behavioral risk factors and obesity among American Indians and Alaska natives of the United States: assessing variations by indian health service region. Prev. Chronic Dis. 19, E05 (2022).
Arrazola, R. A. et al. US cigarette smoking disparities by race and ethnicity - keep going and going!. Prev. Chronic Dis. 20, E45 (2023).
CDC. https://www.cdc.gov/tobacco/campaign/tips/resources/data/cigarette-smoking-in-united-states.html (2024).
Collins, S. E. Associations between socioeconomic factors and alcohol outcomes. Alcohol Res. 38, 83–94 (2016).
Chartier, K. G., Vaeth, P. A. & Caetano, R. Focus on: ethnicity and the social and health harms from drinking. Alcohol Res. 35, 229–237 (2013).
Centers for Disease Control and Prevention. Adult physical inactivity outside of work. (CDC, 2024).
Centers for Disease Control and Prevention. Burden of cigarette use in the U.S. (CDC, 2024).
Guenancia, C. et al. Obesity as a risk factor for anthracyclines and trastuzumab cardiotoxicity in breast cancer: a systematic review and meta-analysis. J. Clin. Oncol. 34, 3157–3165 (2016).
Kaboré, E. G. et al. Association of body mass index and cardiotoxicity related to anthracyclines and trastuzumab in early breast cancer: French CANTO cohort study. PLoS Med. 16, e1002989 (2019).
Reinbolt, R. E. et al. Risk factors for anthracycline-associated cardiotoxicity. Support Care Cancer 24, 2173–2180 (2016).
Chen, J. J., Wu, P. T., Middlekauff, H. R. & Nguyen, K. L. Aerobic exercise in anthracycline-induced cardiotoxicity: a systematic review of current evidence and future directions. Am. J. Physiol. Heart Circ. Physiol. 312, H213–H222 (2017).
Amin, A. M. et al. The efficacy and safety of exercise regimens to mitigate chemotherapy cardiotoxicity: a systematic review and meta-analysis of randomized controlled trials. Cardiooncology 10, 10 (2024).
Bottinor, W. & Hundley, W. G. Does physical activity during cancer treatment preserve exercise capacity?. Circulation 147, 546–548 (2023).
McEwen, B. S. Biomarkers for assessing population and individual health and disease related to stress and adaptation. Metabolism 64, S2–S10 (2015).
Ullmann, E. et al. From allostatic load to allostatic state-an endogenous sympathetic strategy to deal with chronic anxiety and stress? Front. Behav. Neurosci. 13, 47 (2019).
Belsky, D. W. & Snyder-Mackler, N. Invited commentary: integrating genomics and social epidemiology-analysis of late-life low socioeconomic status and the conserved transcriptional response to adversity. Am. J. Epidemiol. 186, 510–513 (2017).
Fredrickson, B. L. et al. Psychological well-being and the human conserved transcriptional response to adversity. PLoS One 10, e0121839 (2015).
Fava, G. A. et al. Clinical characterization of allostatic overload. Psychoneuroendocrinology 108, 94–101 (2019).
McEwen, B. S. & Stellar, E. Stress and the individual. Mechanisms leading to disease. Arch. Intern. Med. 153, 2093–2101 (1993).
Mathew, A. et al. Allostatic load in cancer: a systematic review and mini meta-analysis. Biol. Res. Nurs. 23, 341–361 (2021).
Seeman, T. E., McEwen, B. S., Rowe, J. W. & Singer, B. H. Allostatic load as a marker of cumulative biological risk: MacArthur studies of successful aging. Proc. Natl. Acad. Sci. USA 98, 4770–4775 (2001).
Guidi, J., Lucente, M., Sonino, N. & Fava, G. A. Allostatic load and its impact on health: a systematic review. Psychother. Psychosom. 90, 11–27 (2021).
Shen J., Fuemmeler B. F., Guan Y. & Zhao H. Association of allostatic load and all cancer risk in the SWAN cohort. Cancers 14, 3044 (2022).
Parente, V., Hale, L. & Palermo, T. Association between breast cancer and allostatic load by race: National Health and Nutrition Examination Survey 1999–2008. Psychooncology 22, 621–628 (2013).
Zhao, H., Song, R., Ye, Y., Chow, W. H. & Shen, J. Allostatic score and its associations with demographics, healthy behaviors, tumor characteristics, and mitochondrial DNA among breast cancer patients. Breast Cancer Res. Treat. 187, 587–596 (2021).
Xing, C. Y. et al. Prediagnostic allostatic load as a predictor of poorly differentiated and larger sized breast cancers among black women in the women’s circle of health follow-up study. Cancer Epidemiol. Biomark. Prev. 29, 216–224 (2020).
Cepeda, M. S., Boston, R., Farrar, J. T. & Strom, B. L. Comparison of logistic regression versus propensity score when the number of events is low and there are multiple confounders. Am. J. Epidemiol. 158, 280–287 (2003).
Acknowledgements
The authors acknowledge the efforts of the National Cancer Institute; Information Management Services, Inc.; and the Surveillance, Epidemiology, and End Results (SEER) Program tumor registries in the creation of the SEER-Medicare database. The collection of cancer incidence data used in this study was supported by the California Department of Public Health pursuant to California Health and Safety Code Section 103885; Centers for Disease Control and Prevention’s (CDC) National Program of Cancer Registries, under cooperative agreement 1NU58DP007156; the National Cancer Institute’s Surveillance, Epidemiology and End Results Program under contract HHSN261201800032I awarded to the University of California, San Francisco, contract HHSN261201800015I awarded to the University of Southern California, and contract HHSN261201800009I awarded to the Public Health Institute.
Author information
Authors and Affiliations
Contributions
K.B. and N.M. wrote the main manuscript text and prepared all tables/figures. K.B., M.L.S., E.H.Y., S.M., M.S.S., M.T., J.L., A.B., and N.M. reviewed and approved the manuscript.
Corresponding author
Ethics declarations
Competing interests
The authors declare no competing interests.
Additional information
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary information
Rights and permissions
Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.
About this article
Cite this article
Britten, K., Lipsyc-Sharf, M., Yang, E.H. et al. Socioeconomic disparities in long-term heart failure risk of trastuzumab with or without anthracyclines in early-stage breast cancer: a SEER-Medicare database analysis. npj Breast Cancer (2026). https://doi.org/10.1038/s41523-025-00883-z
Received:
Accepted:
Published:
DOI: https://doi.org/10.1038/s41523-025-00883-z