Triple-negative breast cancer (TNBC) accounts for approximately 15–20% of all breast cancers and remains one of the most aggressive breast cancer subtypes.¹ Unlike hormone receptor-positive or HER2-positive disease, TNBC lacks established therapeutic targets, resulting in a historically poorer prognosis and higher risk of recurrence. Over the last decade, however, immunotherapy has revolutionized the treatment of TNBC, significantly improving clinical outcomes and establishing a new standard of care in both early-stage and metastatic disease. 2-5 Despite these advances, the high cost of immune checkpoint inhibitors remains a major barrier to access in many countries, highlighting the need for strategies that can maintain efficacy while improving affordability.
In early-stage TNBC, neoadjuvant systemic therapy is the preferred approach for patients with cT1c–T4 and/or node-positive disease. 6 It facilitates tumor downstaging, increases the likelihood of breast-conserving surgery, and enables assessment of treatment response through pathological complete response (pCR), a strong predictor of improved long-term outcomes. The addition of pembrolizumab to neoadjuvant chemotherapy significantly improved pCR and event-free survival (EFS), establishing chemoimmunotherapy as the standard of care for high-risk early-stage TNBC. Importantly, the benefit was observed across all predefined clinical subgroups, supporting the broad applicability of this treatment strategy (Figure 1). 2-3
Furthermore, evidence suggests that immunotherapy is most effective when initiated in the neoadjuvant setting. The negative results of the IMpassion030 trial, which evaluated adjuvant atezolizumab after surgery, support the concept that early immune activation in the presence of an intact tumor may be crucial for maximizing treatment benefit. 7 Together, these findings highlight the central role of neoadjuvant chemoimmunotherapy in the management of early TNBC.
The benefits of immunotherapy extend beyond early-stage disease. In metastatic TNBC, immune checkpoint inhibitors combined with chemotherapy have demonstrated significant survival benefits in patients with PD-L1-positive tumors, establishing immunotherapy as a standard first-line treatment option. 4-5 These results further reinforce the importance of immunotherapy across the entire TNBC treatment continuum.
Despite its established role, access to immunotherapy remains a major challenge in many countries, including Georgia, where pembrolizumab is not routinely reimbursed. Consequently, many eligible patients are unable to receive treatment because of financial constraints. This has led to increasing interest in low-dose pembrolizumab strategies. In the KEYNOTE-522 regimen, a patient receives approximately 17 cycles of pembrolizumab at the standard approved dose, representing a substantial financial burden.
In contrast, the PLANeT trial investigated a markedly reduced-dose approach, using pembrolizumab 150 mg during neoadjuvant treatment while achieving encouraging pathological complete response rates comparable to those reported in KEYNOTE-522 (Figure 2). These findings are supported by pharmacokinetic data demonstrating that PD-1 receptor saturation occurs at doses substantially lower than currently approved regimens. Although prospective validation is still required, low-dose pembrolizumab may offer a practical strategy to improve access to effective immunotherapy, particularly in resource-limited settings where affordability remains a major barrier. 8
Looking ahead, advances in TNBC treatment will likely focus on better patient selection for immunotherapy. Biomarkers such as tumor-infiltrating lymphocytes (TILs) and circulating tumor DNA (ctDNA) may help identify patients most likely to benefit from treatment (Figure 3). High TIL levels are associated with enhanced antitumor immune activity and improved responses to immunotherapy, while ctDNA may allow detection of minimal residual disease and early identification of patients at increased risk of relapse (Figure 4). 9-10 The integration of these biomarkers into clinical practice could facilitate a more personalized and cost-effective approach to TNBC management.
In conclusion, immunotherapy has transformed outcomes for patients with both early-stage and metastatic TNBC and is now an essential component of modern treatment. However, access remains a significant challenge in many healthcare systems. Emerging evidence supporting low-dose pembrolizumab offers a promising opportunity to bridge the gap between scientific innovation and real-world affordability. For countries where reimbursement remains limited, such as Georgia, dose optimization may represent an important step toward ensuring that more patients can benefit from life-saving immunotherapy.
Author: Ana Geguchadze, MD, Medical Oncologist, Caucasus Medical Center
