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The late stage of breast cancer at initial diagnosis in patients with cardio-metabolic comorbidities may be partially explained by underlying pathophysiological mechanisms.

Comorbidities have been linked to later stages of breast cancer at the time of diagnosis. The role of biological mechanisms as a contributing factor is unclear. Existing research on the association between cancer and common comorbidities mainly focuses on shared risk factors. Supposing that overlapping pathophysiological mechanisms between comorbidities and cancer impact the cancer stage at diagnosis, it is hypothesized that there will also be differences in the distribution of pathologic prognostic factors by comorbidity status. 

A study published in the journal ecancermedicalscience has analyzed the association between common comorbidities and tumor profile at initial breast cancer diagnosis. Understanding this association could lead to earlier cancer diagnosis, improved management of comorbidities, and thus, improved patient outcomes and reduced healthcare costs.

Study Population and Methodology

A cross-sectional analysis was performed with data from a prior cohort study comprising 2,501 women newly diagnosed with breast cancer. The median age at diagnosis was 53 years. At the time of presentation, 24% of the women had stage I disease, 39% had stage II, 28% had stage III, and 10% had stage IV.

Common Comorbidities in Women

Approximately 65% of women were found to have at least one comorbidity at presentation, of which cardio-metabolic comorbidities were most prevalent. Common comorbidities included dyslipidemia (67.5%), hypertension (44.3%), and diabetes (17.3%). Approximately 18% of participants were obese. Other comorbidities included obstructive airway, thyroid, chronic kidney, and liver diseases, and peptic ulcer.

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Modified Charlson Comorbidity Index
The median score of the modified Charlson Comorbidity Index (CCI) was 1.0. Women 65 years of age or older were more likely to be in the higher quartiles of the CCI. Indian women had a higher prevalence of comorbidities compared with other participants. Hypertension and diabetes mellitus were the most common comorbidities among all ethnic groups, with varied prevalence.

Association of Modified CCI With Tumor Profile

Patients with higher modified CCI scores were more likely to present with larger tumors and a higher lymph node burden. Those with lower CCI scores were more likely to present with favorable biological features like progesterone receptor positive and HER2 negative status. However, tumor grade and HER2 overexpression could not be independently linked to CCI.

Pathologic Profiles With Specific Cardio-Metabolic Conditions

Multiple cardiometabolic conditions were specifically correlated with unfavorable pathologic profiles and, hence, late cancer stages at diagnosis. For example, low HDL levels were linked to large tumors (>5cm) and distant metastases at presentation. Similarly, hypercholesterolemia was inversely related to these factors. Diabetes was significantly associated with a higher lymph nodal burden at diagnosis. Post hoc analyses significantly linked the patients without cardiometabolic comorbidities to favorable tumor profiles, including smaller tumors and the absence of nodal involvement, distant metastases, or HER2 overexpression. Clustering of comorbid conditions was linked to a more unfavorable profile at presentation.


Subramaniam, S., Kong, Y., Yip, C., Thiagarajan, M., Pailoor, J., Zaharah, H., Taib, N. A., See, M., Sarfati, D., & Bhoo-Pathy, N. (2023). Association between pre-existing cardiometabolic comorbidities and the pathological profiles of breast cancer at initial diagnosis: a cross sectional study. PubMed, 17, 1512. https://doi.org/10.3332/ecancer.2022.1512