Immunocompromise in Breast Cancer

Immunocompromise in breast cancer is at the heart of the issue, isn’t it? There may be people with healthy immune systems who get breast cancer; however, with so many documented causes of immunocompromise in breast cancer, we can all agree that a compromised immune system is an adverse effect of BC treatment and must be addressed.

The video below is relatively old, yet raises some important issues about Immunocompromise in breast cancer.

I am a long-term survivor of an incurable blood cancer called multiple myeloma. While BC and MM are very different diseases, it is remarkable to identify so many commonalities.

Breast cancer patients can become immunocompromised through several different pathways, and it often isn’t just one factor—it’s cumulative. Here’s a clear, clinically grounded breakdown you can use for patient education or professional work.

1. The cancer itself (disease-related immune suppression)

Although breast cancer is not classically a “bone-marrow cancer,” the tumor can still impair immune function by:

Chronic inflammation and immune exhaustion (T-cell dysfunction)
Tumor-mediated immune evasion, including:
- Reduced antigen presentation
- Increased regulatory T cells (Tregs)
Advanced or metastatic disease, which is associated with:
- Lower lymphocyte counts
- Impaired innate immunity

👉 This is usually mild to moderate compared with treatment-related effects.

2. Chemotherapy (most common cause)

Cytotoxic chemotherapy is the single biggest driver of immunocompromise in breast cancer.

Mechanisms

Myelosuppression
- Neutropenia (↓ infection defense)
- Lymphopenia (↓ viral and adaptive immunity)
Mucosal barrier injury
- Oral and GI mucositis → bacterial translocation
Disruption of immune memory

Highest-risk regimens

Anthracyclines (e.g., doxorubicin)
Taxanes (e.g., paclitaxel, docetaxel)
Dose-dense regimens
Combination chemo

👉 Risk peaks 7–14 days after each cycle, but cumulative effects can persist for months.

3. Corticosteroids (often underappreciated)

Steroids are widely used in breast cancer care for:

Chemotherapy premedication
Brain metastases
Nausea control
Spinal cord compression
Immune-related adverse events

Immune effects

Suppress T-cell activation
Reduce macrophage and dendritic cell function
Increase susceptibility to:
- Viral infections
- Fungal infections
- Reactivation of latent infections

👉 Even short courses, if repeated, can meaningfully suppress immunity.

4. Targeted therapies

Some modern therapies impair immune function in specific, subtler ways.

HER2-directed therapy

Trastuzumab, pertuzumab
Usually not profoundly immunosuppressive
Risk increases when combined with chemotherapy

CDK4/6 inhibitors (HR+ metastatic disease)

Palbociclib, ribociclib, abemaciclib
Cause neutropenia via cell-cycle arrest
Lower infection risk than chemo but still clinically relevant

5. Radiation therapy

Radiation causes localized and systemic immune effects.

Lymphocyte depletion (highly radiosensitive)
Greater effect when:
- Large fields are treated
- Regional lymph nodes are irradiated
- Treatment is prolonged

👉 Usually mild–moderate alone, but additive with chemo.

6. Hormonal (endocrine) therapy

Endocrine therapy is not classically immunosuppressive, but it can indirectly affect immune resilience.

Estrogen deprivation alters immune signaling
Can contribute to:
- Fatigue
- Sarcopenia
- Bone loss
- Frailty

👉 These changes may increase infection vulnerability over time, especially in older patients.

7. Surgery and postoperative stress

Transient immune suppression from:
- Surgical stress response
- Anesthesia
- Inflammatory cytokine shifts
Higher risk with:
- Major resections
- Postoperative complications

👉 Typically short-lived but relevant perioperatively.

8. Nutritional compromise and microbiome disruption

Very common, often overlooked contributors:

Reduced protein and micronutrient intake
Chemotherapy-related GI toxicity
Antibiotic exposure
Loss of gut microbial diversity

👉 Impairs both innate and adaptive immunity.

9. Comorbidities and patient-specific factors

Baseline factors that magnify treatment effects:

Older age
Diabetes
Obesity
Autoimmune disease
Prior chemotherapy or radiation
Chronic stress and poor sleep

Breast Cancer and the Immune System at MBC Patient Forum 2019

My view is to enhance the BC patient’s immune system with evidence-based, non-conventional therapies such as nutrition, supplementation, lifestyle, and complementary therapies.

Are you a BC survivor? What type of BC? What therapies have you undergone thus far? Please scroll down the page, post a question or comment if you’d like to learn more about evidence-based, non-conventional breast cancer therapies.

Hang in there,

David Emerson

Cancer Survivor
Cancer Coach
Director PeopleBeatingCancer

Immune System Effects on Breast Cancer

Abstract

Breast cancer is one of the most common cancers in women, with the ability to metastasize to secondary organs, which is the main cause of cancer-related deaths. Understanding how breast tumors progress is essential for developing better treatment strategies against breast cancer.

Until recently, it has been considered that breast cancer elicits a small immune response. However, it is now clear that breast tumor progression is either prevented by the action of antitumor immunity or exacerbated by proinflammatory cytokines released mainly by the immune cells.

In this comprehensive review we first explain antitumor immunity, then continue with how the tumor suppresses and evades the immune response, and next, outline the role of inflammation in breast tumor initiation and progression.

We finally review the current immunotherapeutic and immunoengineering strategies against breast cancer as a promising emerging approach for the discovery and design of immune system-based strategies for breast cancer treatment…

Concluding Remarks

The immune system plays a dynamic role in the prevention and progression of breast cancer. Cells such as CTLs and NK cells promote antitumor immunity through targeting breast cancer cells. T_regs, macrophages, MDSCs, and T-helper cells aid in the progression of breast cancer through various mechanisms such as inhibiting the function of cytotoxic T-cells, secreting proinflammatory cytokines, promoting metastasis, and others.

B-cells may have an antitumorigenic role through releasing tumor-neutralizing antibodies, and a protumorigenic role through suppressing antitumor immunity. Inflammation can cause serious damage to the breast tissue and make it easier for the progression of breast cancer through the increase of proinflammatory cytokines such as interleukins and TNF-α.

Immunotherapy and immune engineering are relatively new fields with new discoveries being made constantly. These fields seek to engineer the immune microenvironment or the immune cells to either attack the cancer cells themselves or to release chemotherapeutic drugs to be able to destroy the breast tumor.

There has also been work in the immune engineering field to be able to diagnose breast tumors better and give a more accurate prognosis. There is still a long way to go before many of these treatments become valid therapy possibilities, but the studies show promise to be able to engineer the immune system to destroy the breast tumor and promote antitumor immunity.

Immunocompromise in breast cancer Immunocompromise in breast cancer Immunocompromise in breast cancer