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

It is progressing locally, metastatic breast cancer Significantly associated with higher likelihood of prevalent cardiovascular disease at diagnosis.

study: Diagnosis stages of cardiovascular disease and breast cancer. Image credit: MMD Creative/Shutterstock.com

recent JAMA network open This study assessed whether patients with advanced breast cancer at diagnosis have an increased risk of developing prevalent cardiovascular disease (CVD) compared to patients with early-stage breast cancer.

cardiovascular disease and cancer

Cancer and CVD are the leading causes of death in the United States. These diseases also share established risk factors. Recent studies indicate that there may be a direct causal relationship between CVD and cancer pathogenesis and progression.

Mechanistic studies have demonstrated accelerated tumor growth in association with cardiac remodeling, heart failure, and myocardial infarction (MI).

This suggests the possibility of a direct causal relationship. In the case of breast cancer, CVD induces an immunosuppressive state that promotes accelerated proliferation and spread of breast cancer cells.

About research

Based on the above studies, the current study hypothesized that patients with prevalent CVD may be at a more advanced stage of breast cancer at the time of diagnosis. This case-control study utilized databases linked to Epidemiology, Surveillance, Outcomes, and Medicare.

Female patients at least 66 years of age diagnosed with invasive breast cancer were identified from 2010 to 2019. To account for confounding, patients who underwent a screening mammogram in the 2 years before breast cancer diagnosis were also included.

CVD status was measured 3–24 months before breast cancer diagnosis, which served as the exposure variable. This ensured that concurrent diagnosis was avoided and helped establish a timeline for existing CVD.

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

In addition, comorbidities were identified in the 2 years prior to breast cancer diagnosis. Race and ethnicity data were extracted and included as potential confounders.

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

Research results

For the complete analysis study cohort, 19,292 breast cancer patients were included. Median age was 73 years, with a range of 70 to 79 years.

A total of 8.7% of patients were black, 86.5% were white, and the remainder were of other or unknown races. Non-Hispanics comprised 94.5% of the cohort.

In the matched cohort, 49.1% of individuals had CVD. Of these, 91.5% of patients had breast cancer detected within 13 months to 2 years before being diagnosed.

Patients with early-stage breast cancer were matched with patients presenting with metastatic disease or locally advanced cancer, with each group containing 9,646 patients.

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

Similar findings were observed when examining locally advanced (T3-T4 or N+) disease. Although the results were not statistically significant, there was directional agreement in assessing metastatic disease at diagnosis.

When the primary analysis was stratified by receptor subtype, the observed association was found to be absent in hormone receptor-negative breast cancer. Nevertheless, it was present in hormone receptor-positive breast cancers.

This finding was primarily driven by the strength of the association between ERBB2 negativity (formerly HER2) and hormone receptor positive disease.

conclusion

In summary, the present study demonstrated an association between advanced-stage breast cancer and prevalent CVD at diagnosis. This was independent of factors related to risk sharing and delay in diagnosis.

Future studies should evaluate whether individualized screening approaches are beneficial for CVD patients.

The main limitations of this study concern its observational nature, which does not prove causality. Study designs are also susceptible to residual bias and confounding.

There may also have been misclassification of CVD using procedure codes or diagnoses, and we were unable to account for other important confounders, such as smoking or previous use of hormone replacement therapy.

Additionally, the analysis cohort was comprised primarily of Caucasian patients, which may raise questions about the generalizability of the results. Finally, low estimation power was a problem in some analyses.