Breast Cancer and Immune Checkpoint Inhibitors
Immune checkpoint inhibitors are drugs that enhance the immune system’s ability to attack cancer cells by blocking mechanisms known as “immune checkpoints,” which cancer cells use to evade immune attacks. In breast cancer, these drugs have shown clinical efficacy and received approval, particularly in the following situations:
1. Triple-Negative Breast Cancer (TNBC)
Triple-negative breast cancer is a difficult-to-treat type of breast cancer that is negative for hormone receptors (estrogen receptor and progesterone receptor) and HER2 protein.
- Neoadjuvant and Adjuvant Therapy:
Clinical trials have shown that for patients with PD-L1-positive TNBC, combining pembrolizumab (brand name: Keytruda) with neoadjuvant chemotherapy significantly improves the rate of pathological complete response (pCR), meaning that no cancer cells are found in the tissue removed during surgery. Pembrolizumab has also been approved for adjuvant therapy under certain conditions. - Metastatic or Recurrent TNBC:
For patients with metastatic or recurrent TNBC who are PD-L1 positive, combination therapies using atezolizumab (brand name: Tecentriq) or pembrolizumab with chemotherapy have been approved. Clinical trials have demonstrated improvements in progression-free survival (PFS) and overall survival (OS).
2. Hormone Receptor-Positive, HER2-Negative Breast Cancer
Research on immune checkpoint inhibitors for this subtype has not progressed as much as for TNBC, but recent clinical trials have started to yield promising results.
Currently, immune checkpoint inhibitors are not widely approved as monotherapy or in combination with endocrine therapy for hormone receptor-positive, HER2-negative breast cancer. However, under specific conditions or in treatment-resistant cases, some agents have shown encouraging results in clinical trials. Future studies are highly anticipated.
Important Considerations
- PD-L1 Expression:
The effectiveness of immune checkpoint inhibitors may vary depending on the expression of a protein called PD-L1 in cancer or immune cells. Therefore, PD-L1 testing is generally conducted before treatment. - Side Effects:
Because these drugs activate the immune system, they can cause various immune-related adverse events. These range from mild to severe, requiring careful monitoring and appropriate management. - Personalized Medicine:
Breast cancer treatment varies significantly depending on cancer subtype, stage, and the patient’s condition. The use of immune checkpoint inhibitors also requires careful evaluation by a specialist.
Ongoing Clinical Trials
Numerous clinical trials are actively investigating the combination of immune checkpoint inhibitors with other therapies (chemotherapy, targeted therapy, radiation therapy, etc.) across different stages and subtypes of breast cancer. Based on these results, immunotherapy may become an increasingly important treatment option for many breast cancer patients.
Always consult with your physician regarding treatment decisions, and seek scientifically based information.
Major Clinical Trials
| Trial Name | Target Patients | Main Clinical Outcomes |
|---|---|---|
| KEYNOTE-522 | PD-L1-positive TNBC patients without prior neoadjuvant chemotherapy | Pembrolizumab combined with neoadjuvant chemotherapy significantly improved the pathological complete response (pCR) rate and event-free survival (EFS). |
| IMpassion130 | Metastatic or unresectable PD-L1-positive TNBC patients (chemotherapy-naïve) | Atezolizumab plus nab-paclitaxel significantly extended PFS and OS compared to placebo. |
| KEYNOTE-355 | Metastatic TNBC patients (first or second-line therapy) | In patients with PD-L1 CPS ≥ 1, pembrolizumab plus chemotherapy significantly prolonged PFS compared to placebo. |
| IMpassion131 | Metastatic or unresectable TNBC patients (chemotherapy-naïve) | Atezolizumab plus paclitaxel showed PFS benefit in PD-L1-positive patients, though less pronounced than in IMpassion130. No clear OS benefit observed at present. |
| KEYNOTE-860 (SAFIR02-BREAST) | Metastatic hormone receptor-positive/HER2-negative breast cancer patients with endocrine resistance | Atezolizumab plus capmatinib (a MET inhibitor) showed promising response rates in patients with MET amplification. Though not yet approved, this exploratory study points to future research directions. |
Notes:
- The trials listed above represent key studies of immune checkpoint inhibitors in breast cancer; many others are ongoing or have been reported.
- Clinical outcomes are summarized based on primary endpoints. For detailed results and safety profiles, please refer to published papers or presentations.
- Definitions of PD-L1 positivity and cutoff values may vary between trials.
Glossary:
- Progression-Free Survival (PFS): The length of time during and after treatment that a patient lives without cancer progression.
- Overall Survival (OS): The length of time from the start of treatment until death from any cause.
- Pathological Complete Response (pCR): No viable cancer cells detected in the tissue removed by surgery.
Based on the results of these trials, immune checkpoint inhibitors have been approved for certain breast cancer patients and are now being used in clinical practice. It is essential to discuss treatment options carefully with your physician, considering your individual condition and characteristics.
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