Association Between Cardiovascular Disease and Breast Cancer Stage at Diagnosis

Academic Background

Cardiovascular disease (CVD) and cancer are the two leading causes of mortality in the United States. Although they share many common risk factors, recent studies suggest that CVD may directly promote the occurrence and progression of cancer. Specifically, in breast cancer, CVD may accelerate tumor cell growth and spread by inducing an immunosuppressive state. Therefore, researchers hypothesized that individuals with CVD may be more likely to present with advanced-stage breast cancer at diagnosis. Validating this hypothesis not only helps to understand the potential mechanisms between CVD and cancer but may also provide new insights for personalized breast cancer screening.

Source of the Paper

The study was conducted by Ivan Angelov, Allen M. Haas, Elizabeth Brock, Lingfeng Luo, Jing Zhao, Benjamin D. Smith, Sharon H. Giordano, Nicholas J. Leeper, and Kevin T. Nead. The research team is affiliated with multiple institutions, including the University of Texas MD Anderson Cancer Center and Stanford University School of Medicine. The paper was published on January 2, 2025, in JAMA Network Open, titled Cardiovascular Disease and Breast Cancer Stage at Diagnosis.

Study Design and Methods

Study Design

This study is a population-based case-control study using the SEER-Medicare (Surveillance, Epidemiology, and End Results-Medicare) linked database from 2009 to 2020. The study population consisted of female patients aged 66 years or older diagnosed with invasive breast cancer. The primary objective was to assess whether individuals with advanced-stage breast cancer at diagnosis were more likely to have prevalent CVD compared to those with early-stage breast cancer.

Study Process

1. Cohort Selection: The study identified female patients diagnosed with invasive breast cancer between 2010 and 2019 from the SEER-Medicare database. To control for the impact of healthcare behavior on delayed diagnosis, the study only included patients who had undergone a screening mammogram within two years prior to breast cancer diagnosis.

2. Exposure Variables and Covariates: CVD status was determined from medical records 3 to 24 months prior to breast cancer diagnosis to avoid misclassification of concurrent diagnoses as incidental findings. Other potential confounding factors, such as age, race, Medicaid eligibility, residence, and marital status, were also considered.

3. Statistical Analysis: The study employed a case-control design based on breast cancer stage at diagnosis, comparing early-stage breast cancer (T1-T2, N0, M0) with advanced-stage breast cancer (T3-T4 or N+ or M+). Propensity score matching (PSM) was used to control for confounding factors, and multivariable-adjusted logistic regression models were applied to analyze the association between CVD and breast cancer stage.

Main Results

The study included 19,292 breast cancer patients, of whom 49.1% had prevalent CVD prior to breast cancer diagnosis. After propensity score matching and multivariable adjustment, the study found that patients with advanced-stage breast cancer at diagnosis had a statistically significant increased odds of prevalent CVD (OR=1.10, 95% CI: 1.03-1.17, p=0.007). This association was particularly significant in hormone receptor-positive (HR+) breast cancer (OR=1.11, 95% CI: 1.03-1.19, p=0.006), but not in hormone receptor-negative (HR-) breast cancer (OR=1.02, 95% CI: 0.86-1.21, p=0.83).

Conclusions and Significance

This study is the first to validate the association between CVD and breast cancer stage at diagnosis in a large population, indicating that individuals with CVD are more likely to present with advanced-stage breast cancer at diagnosis. This finding provides new evidence for the potential mechanisms linking CVD and cancer and may inform personalized breast cancer screening strategies. Future research is needed to further validate this association and explore interventions to improve patient outcomes.

Highlights of the Study

1. Key Finding: The study found that CVD is significantly associated with advanced-stage breast cancer at diagnosis, particularly in hormone receptor-positive breast cancer.
2. Methodological Innovation: The study employed propensity score matching and multivariable-adjusted logistic regression models to effectively control for confounding factors.
3. Clinical Significance: The study provides new insights for personalized breast cancer screening, especially for high-risk populations with CVD.

Additional Valuable Information

The study also noted that CVD may accelerate breast cancer growth and spread by inducing an immunosuppressive state. This mechanism has been validated in animal models, further supporting the direct link between CVD and cancer. Future research should further explore this mechanism and investigate interventions to improve patient outcomes.

This study provides new evidence for the association between CVD and cancer and offers important insights for personalized breast cancer screening strategies.