Systemic Treatments for IBC

1. Systemic Treatments: IBC often begins with systemic treatments such as chemotherapy, targeted therapies, and sometimes immunotherapy. These treatments work throughout the entire body to shrink the tumor and target cancer cells that may have spread beyond the breast.
2. Surgery: After systemic treatment, surgery is usually the next step. The standard surgical procedure is a modified radical mastectomy with lymph node dissection, which removes the affected breast tissue and nearby lymph nodes to reduce the risk of recurrence. This type of surgery is typically done if the cancer has not spread to other parts of the body.
3. Radiation Therapy: Radiation therapy follows surgery to target any remaining cancer cells in the breast or chest wall, and may also include the regioal lymph nodes, further reducing the risk of local recurrence.

This aggressive, multi-faceted approach is necessary because IBC tends to spread quickly and may present without a palpable lump in the breast, making it harder to detect early. Understanding each treatment option, its role in managing IBC, potential side effects, and how to manage them can empower you to make informed decisions and feel more prepared for the journey ahead.

• Chemotherapy: Chemotherapy is usually the first line of treatment for IBC. When given before surgery, it is called “neoadjuvant chemotherapy”. The aim of neoadjuvant chemotherapy is to reduce the size of the tumor and eliminate cancer cells throughout the body. This helps make subsequent surgery and radiation more effective.
• Targeted Therapy: Targeted therapies are agents that specifically alter proteins and molecules on cancer cells. For example, for HER2-positive breast cancer, targeted therapies may include anti-HER2 drugs such as Trastuzumab and Pertuzumab.  Targeted therapies can be given in combination with chemotherapy agents.
• Hormonal Therapy: For IBC that is hormone receptor-positive, hormonal therapies may be used to block hormones that fuel cancer growth. These treatments help reduce the risk of recurrence after primary treatments are completed.
• Immunotherapy: Emerging options like immunotherapy are being explored in IBC to harness the body’s immune system to fight cancer cells. This can be particularly beneficial for patients whose cancers do not respond well to conventional treatments.

Why Systemic Treatments Are Essential: Due to IBC’s rapid progression and high likelihood of spreading to other parts of the body, systemic treatments are a cornerstone of its management. They work beyond the primary tumor site, offering a comprehensive approach to controlling the disease and improving outcomes.

Understanding your treatment plan and being aware of potential side effects allows you to better prepare for the journey ahead. We’ll guide you through each of these treatment options, including what to expect, managing side effects, and tips for coping during this challenging time.

Anthracycline and taxane-based chemotherapy are the mainstay treatments for IBC. These drugs are recommended by leading experts around the world. While the core drugs remain consistent, the specific chemotherapy schedules and dosage density may differ across treatment centres.

Anthracyclines

Anthracyclines, such as doxorubicin (Adriamycin) and epirubicin, are potent chemotherapy drugs commonly used as part of first-line treatment for IBC. They work by damaging the DNA within cancer cells, thereby preventing their ability to divide and grow.

• Mechanism: Anthracyclines intercalate into DNA and inhibit topoisomerase II activity, disrupting DNA replication and leading to cancer cell death.
• Application in IBC: Anthracyclines are effective in reducing tumor size and controlling the spread of cancer in IBC patients.
• Side Effects: Common side effects include nausea, hair loss, and increased susceptibility to infections.

Taxanes

Taxanes, such as paclitaxel (Taxol) and docetaxel (Taxotere), are another class of chemotherapy drugs used to treat IBC. They work by stabilizing microtubules within cancer cells, which are essential for cell division and growth.

• Mechanism: Taxanes interfere with microtubule function, leading to cell cycle arrest and ultimately, cell death.
• Application in IBC: Taxanes are effective in targeting rapidly dividing cancer cells, making them a valuable part of combination therapies for IBC.

Side Effects: Side effects may include neuropathy (nerve damage), joint and muscle pain, and fluid retention.

Hormone Therapy & CDK4/6 Inhibitors

For patients with hormone receptor-positive (HR+) IBC, hormone therapy (also referred to as endocrine therapy) is used to block estrogen, which fuels cancer growth. It is often combined with CDK4/6 inhibitors to improve effectiveness.

• Mechanism: Hormone therapy works by blocking estrogen receptors or lowering estrogen levels, preventing cancer cells from using estrogen to grow.
• Application in IBC: Hormone therapy is used in HR+ IBC cases to slow or stop cancer growth. It is often combined with CDK4/6 inhibitors for better effectiveness.
• Side Effects: Common side effects include hot flashes, joint pain, and bone thinning.

CDK4/6 inhibitors are used to slow down cancer cell growth by targeting proteins that regulate the cell cycle. These are typically combined with hormone therapy for HR+ IBC.

• Mechanism: CDK4/6 inhibitors block the proteins CDK4 and CDK6, which are essential for cancer cell division. This stops cancer cells from progressing through the cell cycle.
• Application in IBC: These inhibitors, such as abemaciclib (Verzenio), palbociclib (Ibrance), and ribociclib (Kisqali), may be used in the post-operative setting for selected IBC patients, as demonstrated by the MonarchE trial in high-risk HR+/HER2- breast cancer.
• Side Effects: Common side effects include low blood counts, fatigue, and diarrhea.

Targeted therapies focus on specific molecules involved in cancer growth and progression, offering more precise treatment options compared to traditional chemotherapy. There are currently limited studies on targeted therapies specifically for IBC. Given the high-risk nature of IBC, doctors often use information from studies on other high-risk breast cancers to guide treatment. For IBC, targeted therapies include:

HER2-Targeted Therapy (trastuzumab)

HER2-targeted therapies like trastuzumab (Herceptin) specifically target the HER2 protein found on the surface of some breast cancer cells. These therapies are crucial for HER2-positive IBC, improving outcomes and reducing the risk of recurrence.

• Mechanism: Trastuzumab binds to HER2 receptors, blocking signals that promote cancer cell growth and promoting immune system recognition and destruction of cancer cells.
• Application in IBC: Effective in HER2-positive IBC, targeted therapies like trastuzumab are integral to treatment plans, often used in combination with chemotherapy.
• Side Effects: Potential side effects include infusion reactions and cardiac toxicity.

Pertuzumab

Pertuzumab is a monoclonal antibody that targets and binds to HER2 receptors on cancer cells. It works by inhibiting dimerization (pairing) with other HER family receptors, particularly HER3, which interferes with signaling pathways that promote cancer cell growth and survival. Pertuzumab is often used in combination with trastuzumab and chemotherapy for HER2-positive breast cancers, including IBC.

• Mechanism: Pertuzumab inhibits HER2 dimerization with other HER family members, particularly HER3, blocking downstream signaling pathways that contribute to cancer cell proliferation.
• Application in IBC: Used in combination with trastuzumab and chemotherapy, pertuzumab enhances the effectiveness of HER2-targeted therapies in treating HER2-positive IBC.
• Side Effects: Common side effects include infusion reactions, diarrhea, and potential cardiac dysfunction.

• For patients with HER2+ IBC:

• Who achieved a pCR: Adjuvant pertuzumab (Perjeta) and trastuzumab (Herceptin) are recommended if the cancer responds well to treatment.
• HER2+ IBC patients who did NOT achieve a pCR: If the cancer does not respond well, then T-DM1 (trastuzumab emtansine) may be considered.

Recent advancements have introduced new avenues for treating IBC, including immunotherapy and PARP inhibitors. These therapies offer promising alternatives or complements to traditional approaches, particularly in targeted patient populations.

Immunotherapy

While not yet fully established in IBC treatment protocols, recent research on non-IBC breast cancer has shown promising results with immune checkpoint inhibitors (e.g., pembrolizumab, nivolumab), producing high response rates. Though not yet specific to IBC, these findings suggest a potential future role for immunotherapy in treating IBC.

Research is ongoing to explore its efficacy in harnessing the immune system to fight cancer, including IBC.

• Mechanism: Immunotherapy works by enhancing the body’s immune response against cancer cells, using agents like immune checkpoint inhibitors or CAR-T cell therapy.
• Application in IBC: Exploring efficacy and safety in clinical trials. Hopeful future treatment option.
• Side Effects: Potential side effects include immune-related adverse events, such as inflammation of organs like the lungs, liver, and intestines.

PARP Inhibitors

PARP inhibitors, such as olaparib (Lynparza), are targeted therapies used in the treatment of certain types of breast cancer, including IBC. They exploit vulnerabilities in cancer cells that have defects in DNA repair mechanisms, such as those caused by mutations in BRCA1 and BRCA2 genes.

• Mechanism: PARP inhibitors block PARP enzymes, preventing cancer cells from repairing DNA damage and leading to their death.
• Application in IBC: PARP inhibitors are particularly beneficial for patients with BRCA mutations, offering a targeted approach to treatment.
• Side Effects: Common side effects include nausea, fatigue, and potential risks of bone marrow suppression.

Understanding the mechanisms and applications of these systemic treatments is crucial for managing IBC effectively. By targeting cancer cells throughout the body, these therapies aim to control the disease, improve outcomes, and enhance the quality of life for patients with IBC.

Current Challenges:

• IBC’s Nature: IBC frequently spreads to distant parts of the body and has a generally poor prognosis, underscoring the need for new and more effective treatments.
• High-Dose Chemotherapy: High-dose chemotherapy with autologous hematopoietic stem cell transplantation (AHSCT) has been found to be too toxic without clear benefits.
• Standard Treatments: Currently, only anti-HER2 therapies (pertuzumab, trastuzumab, T-DM1) are integrated into the standard treatment protocol for IBC.

Future Directions:

• Need for New Approaches: There is an urgent need for new treatment strategies, especially those tailored specifically for IBC.
• Global Collaboration: Utilizing a global, multicenter approach for IBC-specific clinical trials can enhance the success of these trials, leading to improved treatment outcomes for IBC patients.

Source: Update on systemic treatment for newly diagnosed inflammatory breast cancer – PMC