Are individuals with advanced breast cancer more likely to have cardiovascular disease?

By Dr. Priyom Bose, Ph.D.Reviewed by Lily Ramsey, LLMJan 7 2025

Locally advanced or metastatic breast cancer at diagnosis is significantly associated with higher odds of prevalent cardiovascular disease.

Study: Cardiovascular Disease and Breast Cancer Stage at Diagnosis. Image Credit: MMD Creative/Shutterstock.com

A recent JAMA Network Open study assessed whether individuals with advanced breast cancers were at a greater risk of having prevalent cardiovascular disease (CVD) relative to early-stage breast cancer patients at the time of diagnosis.

Cardiovascular disease and cancer

In the United States, cancer and CVD are the leading causes of mortality. These diseases also share well-established risk factors. Recent research has indicated that there could be a direct causal link between CVD and the etiology and progression of cancer.

Mechanistic investigations have documented that tumor growth is accelerated in the context of cardiac remodeling, heart failure, and myocardial infarction (MI).

This suggests a potential direct causal link. In the case of breast cancer, CVD induces an immunosuppressive state which facilitates the accelerated growth and spread of breast tumor cells.

About the study

Building on the research described above, the current study hypothesized that prevalent CVD patients could be at more advanced stages of breast cancer at diagnosis. For this case-control study, epidemiology, surveillance, and results–Medicare-linked databases were utilized.

Female patients diagnosed with invasive breast cancer and of at least 66 of age were identified between 2010 and 2019. To account for confounding, patients with a screening mammogram in the two years prior to breast cancer diagnosis were included.

CVD status was determined from 3 to 24 months prior to breast cancer diagnosis, and this served as the exposure variable. This ensured the avoidance of concurrent diagnoses and helped establish a timeline of pre-existing CVD.

The main outcome of interest was the odds of locally advanced or metastatic breast cancer status at diagnosis.

Furthermore, comorbidities were identified in the two years preceding the breast cancer diagnosis. Race and ethnicity data were extracted and included as potential confounding factors.

The primary analysis compared CVD status among individuals at advanced stages of breast cancer (T3-T4 or N+ or M+) with those at earlier stages (T1-T2 and N0 and M0). Patients with metastatic (M+) disease and locally advanced (T3-4 or N+ and M0) disease were examined separately.

Study findings

Concerning the full analytic study cohort, it included 19,292 individuals with breast cancer. The median age was 73 years and ranged between 70 and 79 years.

A total of 8.7% of the patients belonged to the Black ethnicity, 86.5% were White, and the remainder had other or unknown race. Non-Hispanics accounted for 94.5% of the cohort.

In the matched cohort, 49.1% of individuals had CVD. Among these, 91.5% of the patients had the disease detected in the 13-month to two-year window prior to the diagnosis of breast cancer.

Individuals with early-stage breast cancer were matched with those showing metastatic disease or locally advanced cancers, and there were 9646 individuals in each group.

The primary analysis revealed that patients with metastatic or locally advanced breast cancer at diagnosis had statistically significantly higher odds of prevalent CVD.

When examining locally advanced (T3-T4 or N+) disease, a similar finding was noted. The results were not statistically significant, but they were directionally consistent while evaluating metastatic disease at diagnosis.

When the primary analysis was stratified by receptor subtype, it was noted that the observed association was absent in hormone receptor-negative breast cancer. Still, it was present in hormone receptor-positive breast cancer.

The strength of the association between ERBB2-negative (formerly HER2) and hormone receptor-positive disease drove this finding mainly.

Conclusions

In sum, the current study documented an association between advanced-stage breast cancer and prevalent CVD at diagnosis. This was independent of factors associated with shared risk and delayed diagnosis.

Future research should assess whether personalized screening approaches would be beneficial for individuals with CVD.

The main limitation of this study concerns its observational nature, which does not demonstrate causality. The study design is also susceptible to residual bias and confounding.

There could also have been CVD misclassification using procedure codes and diagnoses, and it was not possible to account for some other important confounding factors, like smoking and prior hormone replacement therapy use.

Furthermore, the generalizability of the findings could be questioned because the analytic cohort was comprised primarily of White patients. Finally, low estimation power was also an issue in some of the analyses.