Pembrolizumab for Triple-Negative Breast Cancer: An Overview

Triple-negative breast cancer (TNBC) - defined by the absence of oestrogen receptor, progesterone receptor, and HER2 expression - is the most aggressive breast cancer subtype and historically the most difficult to treat. Pembrolizumab has established itself as an important treatment option in TNBC across both early and advanced disease settings.

Why TNBC responds to immunotherapy

TNBC is more immunogenic than hormone receptor-positive breast cancers - it tends to have higher tumour mutation burden, more tumour-infiltrating lymphocytes, and higher PD-L1 expression. These features make it a more promising target for checkpoint inhibitor therapy than other breast cancer subtypes. The tumour microenvironment in TNBC is often highly inflamed, providing a context where releasing the PD-1 brake can have meaningful anti-tumour effect.

KEYNOTE-522: Early TNBC

KEYNOTE-522 evaluated pembrolizumab added to neoadjuvant chemotherapy (chemotherapy given before surgery) in patients with early, high-risk TNBC. The primary endpoint was pathological complete response (pCR) - the absence of residual tumour in the surgically removed tissue. Adding pembrolizumab to chemotherapy increased pCR rates from 51% to 65% - a substantial difference in a metric associated with long-term outcomes. Event-free survival was also significantly improved. Pembrolizumab continued as adjuvant treatment after surgery. KEYNOTE-522 established pembrolizumab as a standard component of treatment for early high-risk TNBC.

KEYNOTE-355: Metastatic TNBC

In the first-line metastatic setting, KEYNOTE-355 demonstrated that adding pembrolizumab to chemotherapy significantly improved progression-free survival in patients with CPS 10 or higher. Pembrolizumab combined with nab-paclitaxel, paclitaxel, or gemcitabine plus carboplatin is now approved for PD-L1-positive (CPS 10+) locally advanced unresectable or metastatic TNBC as first-line treatment.

PD-L1 testing in TNBC

For the metastatic indication, PD-L1 CPS testing is required. A CPS of 10 or higher is the threshold for pembrolizumab eligibility in this setting. For early-stage disease (KEYNOTE-522 indication), PD-L1 status is not required for eligibility - pembrolizumab was beneficial regardless of PD-L1 expression in the neoadjuvant setting.