Does Breast Cancer Cause High White Blood Cell Count?

White blood cell (WBC) count is an indicator of immune system activity, particularly in response to infections, inflammation, and disease. In cancer, including breast cancer, WBC levels can change due to tumor-related inflammation or treatment effects. Understanding this relationship requires examining how cancer influences immune responses and WBC fluctuations.

Role Of White Blood Cells In The Immune System

White blood cells (WBCs), or leukocytes, defend against pathogens, abnormal cells, and foreign substances. Produced in the bone marrow, they circulate through the bloodstream and lymphatic system, identifying and neutralizing threats. Unlike red blood cells, which transport oxygen, WBCs specialize in immune functions, with distinct subtypes coordinating immune responses.

Some WBCs, such as cytotoxic T cells and natural killer (NK) cells, target abnormal cells, preventing unchecked proliferation. Others, like macrophages and dendritic cells, process and present antigens to activate broader immune responses. This network helps distinguish normal from abnormal cells, reducing cancer risk.

WBCs also regulate inflammation, which can be both protective and harmful. When injury or infection occurs, leukocytes release cytokines that recruit immune cells for containment and repair. However, chronic inflammation can contribute to disease progression, including cancer. Regulatory T cells help prevent excessive inflammation that could damage healthy tissues.

Mechanisms Of Inflammation In Cancer

Inflammation influences cancer initiation, progression, and metastasis by creating an environment rich in growth factors and cytokines that promote cellular proliferation. In breast cancer, chronic inflammation can result from hormonal imbalances, adipose tissue dysfunction, and immune activation within the tumor microenvironment.

Key inflammatory pathways, such as nuclear factor-kappa B (NF-κB) and signal transducer and activator of transcription 3 (STAT3), are often activated in cancerous tissues. NF-κB regulates immune responses and promotes cytokine production, including interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), which enhance tumor survival and angiogenesis. STAT3 activation supports tumor growth while suppressing immune defenses.

The tumor microenvironment, composed of cancer cells, stromal cells, and immune infiltrates, sustains inflammation. Tumor-associated macrophages (TAMs) secrete immunosuppressive factors like IL-10 and transforming growth factor-beta (TGF-β), dampening cytotoxic immune responses. Neutrophils in tumors can release neutrophil extracellular traps (NETs), which facilitate metastasis by aiding cancer cell adhesion to distant tissues.

Correlation Between Breast Cancer And WBC Levels

WBC levels can fluctuate in breast cancer patients due to systemic inflammation, stress responses, infections, or treatment effects. While not a definitive marker of breast cancer, elevated WBC counts have been linked to tumor burden and disease progression.

Some studies suggest that persistently high WBC counts correlate with aggressive tumor behavior. A retrospective analysis in Breast Cancer Research and Treatment found that patients with elevated pre-treatment WBC levels had a higher likelihood of lymph node involvement and metastasis. This may result from cancer-induced inflammation stimulating bone marrow activity and increasing leukocyte production.

Beyond inflammation, circulating tumor cells (CTCs) can alter blood cell composition. CTC interactions with the circulatory system may trigger immune cell recruitment or hematopoietic signaling changes, leading to leukocytosis in some patients. While not universally observed, this phenomenon is more common in advanced breast cancer cases.

Variation Among Different Types Of WBC

White blood cells include several subtypes, each with distinct functions. Variations in WBC populations can provide insights into disease progression, treatment effects, and systemic inflammation.

Neutrophils

Neutrophils, the most abundant WBCs, contribute to inflammation and tissue remodeling. Elevated neutrophil levels are common in advanced breast cancer cases. The neutrophil-to-lymphocyte ratio (NLR) has been studied as a prognostic marker, with higher values linked to poorer outcomes. A JAMA Oncology study found that breast cancer patients with an NLR above 4.0 had lower survival rates.

Neutrophils promote tumor progression by releasing proteolytic enzymes like matrix metalloproteinases (MMPs), which aid cancer cell invasion. They also secrete vascular endothelial growth factor (VEGF), supporting angiogenesis. While neutrophilia is not exclusive to cancer, its presence may indicate an inflammatory tumor microenvironment.

Lymphocytes

Lymphocytes, including T cells, B cells, and NK cells, are crucial for immune surveillance. Their levels vary in breast cancer patients depending on disease stage and immune engagement. Lower lymphocyte counts have been linked to worse prognosis. Research in Clinical Cancer Research found that breast cancer patients with lymphopenia (lymphocyte count below 1.0 × 10⁹/L) had higher recurrence risk and reduced survival rates.

Lymphocyte decline may result from chronic inflammation, tumor-induced immunosuppression, or chemotherapy effects. Conversely, tumor-infiltrating lymphocytes (TILs) have been associated with better responses to immunotherapy and chemotherapy, particularly in triple-negative breast cancer (TNBC), indicating an active anti-tumor immune response.

Monocytes

Monocytes, which differentiate into macrophages and dendritic cells, regulate immune responses and tissue repair. Elevated monocyte counts are observed in some breast cancer patients, particularly those with metastatic disease. A Cancer Immunology Research study reported that patients with monocyte counts above 0.8 × 10⁹/L had a higher likelihood of disease progression.

Monocytes are recruited to tumors, where they become TAMs, secreting immunosuppressive cytokines and promoting angiogenesis. They also interact with circulating tumor cells (CTCs), enhancing immune evasion and metastasis. While monocyte elevation is not exclusive to cancer, it may indicate an immune landscape favoring tumor persistence.

Eosinophils

Eosinophils, primarily involved in allergic reactions and parasitic infections, have an unclear role in breast cancer. Some studies suggest eosinophil levels may fluctuate in response to tumor-associated inflammation. A OncoImmunology analysis found that breast cancer patients with eosinophil counts above 0.5 × 10⁹/L had slightly improved prognosis, particularly in hormone receptor-positive subtypes.

Eosinophils can release cytotoxic granules that damage tumor cells and recruit other immune cells. However, eosinophilia is uncommon in breast cancer, and its clinical significance remains under investigation.

Basophils

Basophils, the least common WBCs, participate in allergic responses and histamine release. Their role in breast cancer is not well understood, but some evidence suggests alterations in basophil levels among patients. A Frontiers in Oncology study noted that chemotherapy patients often experience transient basopenia (basophil count below 0.02 × 10⁹/L) due to bone marrow suppression.

Some reports suggest basophils contribute to tumor-promoting inflammation by releasing histamine and cytokines that support angiogenesis. While basophil changes are unlikely to serve as primary biomarkers, they may provide additional context in evaluating immune status.

Other Factors That Influence WBC Count

Breast cancer can influence WBC levels, but many other factors contribute to fluctuations. Medical conditions, medications, and physiological stress complicate WBC interpretation in cancer patients.

Infections often cause leukocytosis as the immune system responds. Cancer patients, especially those undergoing chemotherapy, are at higher infection risk due to immunosuppression, which can lead to elevated or decreased WBC counts. Certain medications, including corticosteroids and granulocyte colony-stimulating factor (G-CSF), can artificially increase WBC production. Chronic inflammatory conditions such as rheumatoid arthritis or inflammatory bowel disease may also elevate WBC counts.

Stress, both physiological and psychological, affects leukocyte levels. Surgery, trauma, or emotional distress can temporarily raise WBC counts due to cortisol and epinephrine release. Smoking is also linked to elevated WBC levels. Given these variables, a comprehensive evaluation of medical history, concurrent conditions, and treatment status is essential to determine whether WBC changes are cancer-related or influenced by external factors.