and face a poorer prognosis than patients with PD-L1–positive tumors, according to a study presented at ESMO Breast Cancer 2022, a meeting of the European Society for Medical Oncology.
“The newly distinct quadruple negative breast cancer subtype could be considered the breast cancer subtype with the poorest outcome,” wrote the authors, who were led by Loay Kassem, MD, a clinical oncology consultant at Cairo (Egypt) University.
Triple-negative breast cancer (TNBC) accounts for 15%-20% of all breast cancers. It tends to be more aggressive and difficult to treat than other subtypes.
Prior research has shown the expression of PD-L1 in tumors is predictive of immunotherapy response in patients with metastatic TNBC. The checkpoint inhibitor pembrolizumab (Keytruda, Merck) was approved by the Food and Drug Administration in 2021 for high-risk, early-stage, triple-negative breast cancer in combination with neoadjuvant chemotherapy, and then continued as a single treatment after surgery.
To determine whether PD-L1 expression could also predict response to chemotherapy in with nonmetastatic TNBC, the researchers conducted a systematic review and meta-analysis of 19 studies that included a total of 2,319 patients with nonmetastatic TBNC. The team examined whether PD-L1 expression could predict pathological complete response to neoadjuvant chemotherapy. PD-L1–positive TNBC were found to be significantly associated with a higher probability of achieving a pathological complete response with neoadjuvant chemotherapy. Long-term studies have shown that PD-L1 positivity was associated with better disease-free survival and overall survival than PD-L1–negative patients.
The researchers also examined RNA sequence data, which showed that PD-L1 expression was indicative of higher levels of expression of key immune-related genes that mediate response to chemotherapy in TNBC.
Dr. Kassem and colleagues suggest that quadruple-negative breast cancer defined by a lack of PD-L1 expression is a distinct subtype of breast cancer associated with the poorest outcomes. Another quadruple-negative breast cancer – a subtype of TNBC where patients lack expression of the androgen receptor, has also been associated with more aggressive disease and poorer response to treatment.
The authors report no funding or conflicts of interest.