Which TNBC Patients Benefit From Adjuvant Chemo?

TOPLINE:

Patients with early-stage triple-negative breast cancer (TNBC) and high immune infiltration showed improved disease-free survival (DFS) with adjuvant capecitabine. These “immune-hot” patients had a 5-year DFS rate of 96.9% compared with 79.4% in the control group.

METHODOLOGY:

• In some studies, adding extended capecitabine to standard adjuvant chemotherapy has been shown to improve DFS in patients with early-stage TNBC, and one subset analysis suggested improved outcomes were most strongly associated with high immune infiltration.
• Researchers conducted a retrospective analysis of CBCSG010, a randomized phase 3 clinical trial, to identify the specific population that benefited from adjuvant capecitabine by analyzing the immune infiltration status of the tumors.
• The CBCSGO10 study of 585 patients originally found adjuvant capecitabine improved 5-year survival in patients with TNBC by 5.9%.
• This analysis included 207 patients (capecitabine arm, n = 104; control arm, n = 103) with serial formalin-fixed, paraffin-embedded tumor specimens, of which RNA sequencing data were available from 36 patients (capecitabine, n = 24; control, n = 12).
• Transcriptome data on the tumor microenvironment were validated with immunohistochemical staining of two markers, programmed death-ligand 1 (PD-L1) and CD8, as well as stromal tumor-infiltrating lymphocytes (sTILs); patients with high PD-L1, CD8, and sTIL expression levels were defined as “immune hot.”

TAKEAWAY:

• Patients with TNBC and high immune infiltration treated with capecitabine had a 5-year DFS rate of 96.9% compared with 79.4% in the control group (hazard ratio [HR], 0.13; 95% CI, 0.03-0.52; P = .049).
• In the capecitabine group, the immune-hot patients had a higher 5-year DFS rate (96.9%) compared with immune-cold patients (76.4%; HR, 0.11; 95% CI, 0.04-0.29; P = .028).
• Gene ontology analysis showed greater enrichment of immune-related pathways in patients without recurrence in the capecitabine group, as well as higher expression of TYMP, a key liver enzyme in the metabolism of capecitabine.
• High expression levels of immune biomarkers PD-L1, CD8, and sTILs were associated with significantly improved DFS in the capecitabine group.

IN PRACTICE:

“Our study suggested that immune-hot patients with TNBC are more likely to benefit from adjuvant capecitabine and that combining immunotherapy with chemotherapy may be expected to be more effective in immune-hot patients,” wrote the study authors.

SOURCE:

The study was led by Wenya Wu, MMed, and Yunsong Yang, MD, at the Department of Breast Surgery, Fudan University Shanghai Cancer Center in Shanghai, People’s Republic of China. It was published online in October 2024 in JNCCN — Journal of the National Comprehensive Cancer Network.

LIMITATIONS:

The retrospective nature of the sample collection limited the availability of RNA sequencing data. External verification was challenging due to limited accessibility of transcriptome data from patients treated with additional adjuvant capecitabine or standard chemotherapy alone. The criteria for identifying immune-hot tumors require further exploration and determination.

DISCLOSURES:

This study was funded by the National Natural Science Foundation of China, China Postdoctoral Science Foundation, and Shanghai Science and Technology Development Foundation. The authors disclosed no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.