European Journal of Cardiovascular Medicine

Breast carcinoma is one of the most prevalent malignancies among women worldwide and represents a major public health concern due to its increasing incidence and mortality rates (1). The biological behavior of breast cancer is influenced by a variety of molecular and histological factors, with tumor grade serving as an important prognostic indicator (2). Tumor grading reflects the degree of cellular differentiation and correlates with tumor aggressiveness, response to therapy, and overall prognosis (3).

Emerging evidence suggests that inflammation plays a pivotal role in cancer development and progression. Inflammatory responses within the tumor microenvironment can promote proliferation, angiogenesis, and metastasis through various cytokines and immune mediators (4,5). Several systemic inflammatory markers such as C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and neutrophil-to-lymphocyte ratio (NLR) have been proposed as potential prognostic tools in different cancers, including breast carcinoma (6,7).

CRP is an acute-phase protein synthesized by the liver in response to pro-inflammatory cytokines, and its elevated levels have been linked to poor outcomes in various malignancies (8). Similarly, an increased NLR indicates an imbalance between neutrophil-mediated tumor-promoting inflammation and lymphocyte-mediated anti-tumor immunity (9). ESR, a nonspecific marker of inflammation, has also shown prognostic relevance in cancer settings (10).

Despite these associations, limited studies have explored the correlation between these inflammatory markers and histological tumor grades in breast carcinoma. Identifying such relationships may offer simple, cost-effective methods for risk stratification and personalized treatment approaches. This study aims to evaluate the correlation between selected inflammatory markers (CRP, ESR, and NLR) and tumor grade in patients with breast carcinoma

A cross-sectional observational study was conducted in the Department of Pathology at a tertiary care hospital over a period of 12 months. The study included 100 female patients with histologically confirmed invasive breast carcinoma, diagnosed through core needle biopsy or excision specimens. Informed consent was collected from all participants prior to inclusion.

Inclusion criteria

Involved patients aged between 30 and 70 years with no prior history of chemotherapy, radiotherapy, or major systemic illness.

Exclusion criteria

Were patients with known autoimmune disorders, infections, inflammatory conditions, or any malignancies other than breast carcinoma.

Prior to initiation of any cancer-specific treatment, blood samples were drawn under aseptic conditions. The following inflammatory markers were assessed:

• C-Reactive Protein (CRP): Measured using a high-sensitivity immunoturbidimetric method.
• Erythrocyte Sedimentation Rate (ESR): Determined by the Westergren method.
• Neutrophil-to-Lymphocyte Ratio (NLR): Calculated from a complete blood count using an automated hematology analyzer.

Tissue specimens were processed and stained with hematoxylin and eosin. Tumor grading was done according to the Nottingham Histologic Score (Elston-Ellis modification of the Bloom-Richardson grading system), assessing tubule formation, nuclear pleomorphism, and mitotic count.

The patients were then stratified into three groups based on tumor grade: Grade I (well-differentiated), Grade II (moderately differentiated), and Grade III (poorly differentiated).

Statistical Analysis

Was carried out using SPSS version 25.0. Descriptive statistics were used for baseline variables. Continuous variables were expressed as mean ± standard deviation (SD). The association between inflammatory markers and tumor grade was analyzed using Analysis of Variance (ANOVA) and Pearson’s correlation coefficient. A p-value < 0.05 was considered statistically significant.

A total of 100 patients with histologically confirmed breast carcinoma were included in the study. The age of the participants ranged from 32 to 68 years, with a mean age of 48.7 ± 8.4 years. Most patients presented with Grade II tumors (45%), followed by Grade I (30%) and Grade III (25%) (Table 1).

Table 1: Distribution of Patients Based on Tumor Grade

The mean values of inflammatory markers—CRP, ESR, and NLR—were found to increase progressively with higher tumor grades. Patients with Grade III tumors had significantly elevated CRP levels (11.2 ± 2.5 mg/L), ESR (47.8 ± 10.2 mm/hr), and NLR (4.8 ± 1.2) compared to Grade I tumors, which showed lower levels (CRP: 4.3 ± 1.1 mg/L, ESR: 21.5 ± 6.3 mm/hr, NLR: 2.1 ± 0.6) (Table 2).

Table 2: Comparison of Mean Inflammatory Marker Levels across Tumor Grades

Statistical analysis using ANOVA revealed a significant difference in CRP, ESR, and NLR values across the three tumor grades (p < 0.001). Pearson’s correlation showed a positive correlation between tumor grade and each inflammatory marker, with correlation coefficients of r = 0.65 for CRP, r = 0.61 for ESR, and r = 0.58 for NLR.

These findings suggest that higher tumor grades are associated with elevated levels of systemic inflammation (Tables 1 and 2).

The present study explored the relationship between systemic inflammatory markers—CRP, ESR, and NLR—and histopathological tumor grade in breast carcinoma. Our results demonstrate a significant rise in inflammatory marker levels with increasing tumor grade, indicating a potential role of systemic inflammation in tumor aggressiveness and progression.

Breast carcinoma remains one of the most commonly diagnosed cancers and a leading cause of cancer-related mortality in women globally (1). Tumor grade, based on histological characteristics, has long been established as an independent prognostic factor in breast cancer, with higher grades indicating more aggressive behavior and poorer outcomes (2,3). The integration of systemic biomarkers such as inflammatory markers could enhance current prognostic models.

Chronic inflammation contributes to carcinogenesis through multiple mechanisms including genomic instability, angiogenesis, and immune evasion (4,5). CRP, a hepatic acute-phase reactant, is regulated by interleukin-6 and serves as a general marker of systemic inflammation (6). In this study, patients with high-grade tumors exhibited significantly elevated CRP levels, consistent with findings reported by Allin et al. and Heikkilä et al., who found high CRP levels associated with poor prognosis in breast and other solid tumors (7,8).

Similarly, ESR, though a nonspecific marker, reflects ongoing systemic inflammation and has shown utility in cancer prognosis (9). Our results align with those of Danesh et al., who observed a correlation between elevated ESR and increased cancer risk and mortality (10).

NLR is another emerging inflammatory index representing the balance between pro-tumor neutrophilic activity and anti-tumor lymphocytic function (11). High NLR has been linked with poor overall and disease-free survival in breast cancer (12,13). Our study reinforces these findings, showing significantly higher NLR in patients with Grade III tumors.

These associations could be attributed to the role of inflammatory cells and mediators in supporting tumor microenvironment remodeling, angiogenesis, and metastatic spread (14,15). Neutrophils, in particular, can secrete cytokines and proteases that facilitate tumor invasion, while lymphocyte depletion may signify a weakened immune response (6,7).

Several studies have emphasized the prognostic relevance of these markers in breast carcinoma. A meta-analysis by Templeton et al. concluded that high NLR is a predictor of poor outcomes across various solid tumors, including breast cancer (8). Meanwhile, elevated CRP and ESR have been independently associated with larger tumor size, lymph node metastasis, and higher histologic grade (9).

The key strength of this study lies in its focus on pre-treatment inflammatory status, which minimizes confounding due to therapeutic interventions. However, limitations include a relatively small sample size and lack of long-term follow-up data on survival and recurrence. Multicentre studies with larger cohorts and longitudinal design are needed to validate these findings and establish cut-off values for clinical application (2).

In conclusion, our findings support the potential utility of CRP, ESR, and NLR as accessible, low-cost prognostic biomarkers in breast carcinoma. Their integration into clinical practice may help refine risk stratification and inform treatment planning alongside conventional histopathological grading.

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