High tumor expression of CTLA4 identifies lymph node-negative basal-like breast cancer patients with excellent prognosis.

Abstract

Background: Tumor immune cell infiltration is a favorable prognostic factor in triple-negative breast cancer. Most triple-negative tumors belong to the aggressive basal-like subtype. We hypothesized that immune gene expression may identify low-risk patients for whom adjuvant chemotherapy can be de-escalated.

Methods: The expression of 753 immune-related genes was analyzed in tumor biopsies from 45 patients with basal-like disease and no lymph node metastases (Oslo1 cohort) and evaluated for prognostic value. Findings were validated in two independent cohorts. Oslo1 biopsies were also analyzed for tumor-infiltrating lymphocytes (TIL) and tertiary lymphoid structures (TLS).

Results: Here we show that a high expression of CTLA4 (above 63^rd percentile) is associated with an excellent prognosis in the Oslo1 cohort. None of the patients in the CTLA4^high group suffered disease recurrence (median follow-up 7.4 years) or breast cancer-related death (median follow-up 17.7 years). Analysis of the SCAN-B (n = 233; 97% without distant recurrence in CTLA4^high group) and METABRIC cohorts (n = 155; 93% disease-specific survival in CTLA4^high group) validates this finding, which also applies to patients who did not receive chemotherapy. CTLA4 expression correlates with TIL score and TLS levels (Oslo1 cohort), but no TIL^low/CTLA4^high patients died from breast cancer, suggesting that the CTLA4 readout identifies low-risk patients not captured by TIL assessment.

Conclusions: A high primary tumor expression of CTLA4 identifies patients with an excellent prognosis, for whom standard chemotherapy may be de-escalated or omitted.