TIL Levels Linked to ERBB2+ Breast Cancer Survival Outcomes

TOPLINE:

Higher tumor-infiltrating lymphocyte (TIL) levels were independently associated with improved overall survival in patients with early-stage ERBB2-positive breast cancer. Each 5% increase in TILs was associated with an 11% reduced risk for death, according to a 10-year follow-up analysis of the phase 3 ShortHER trial.

METHODOLOGY:

• TILs have been associated with pathological complete response rates and risk of relapse in ERBB2-positive breast cancer, but it’s unclear whether TIL levels are also associated with survival outcomes.
• The ShortHER trial is a phase 3 noninferiority randomized trial, involving 1254 patients with ERBB2-positive breast cancer who were randomly assigned to receive adjuvant trastuzumab for either 9 weeks (short arm) or 1 year (long arm) alongside chemotherapy.
• The primary endpoint of the trial was disease-free survival (DFS). At a median follow-up of 6 years, researchers reported on the possible prognostic role of TILs and demonstrated higher TIL levels were positively associated with improved rates of distant DFS.
• This follow-up analysis included 866 women (median age, 56 years) with available TILs and examined the effect of TILs on survival outcomes, including overall survival, at a median follow-up of about 9 years.

TAKEAWAY:

• Each 5% increase in TILs was associated with a 13% reduction in the risk for distant DFS events (hazard ratio [HR], 0.87; P = .001) and an 11% reduction in the risk for death (HR, 0.89; P = .01).
• The 10-year overall survival rate was 91.3% for patients with TILs ≥ 20%, 93.3% for those with TILs ≥ 30%, and 98.1% for those with TILs ≥ 50%, showing progressively better outcomes with higher TIL levels.
• Patients with TILs P for interaction = .01).
• Similarly, patients with TILs under 20% showed better overall survival with long vs short treatment (10-year overall survival, 91.3% vs 86.9%; HR, 1.36), while those with TILs ≥ 20% showed a numerically better overall survival with short vs long treatment (10-year rate, 93.1% vs 89.3%; HR, 0.36; P for interaction = .06).

IN PRACTICE:

“This updated analysis of the ShortHER randomized clinical trial is, to our knowledge, the first report of a strong independent association of TILs with [overall survival] for patients with ERBB2-positive early breast cancer,” the authors wrote. The study demonstrated that, at a median follow-up of 9 years, “there was a statistically significant association between increased TIL density and improved [overall survival] and [DFS].” Moreover, the authors added, “these data suggest that patients with high TILs at the 20% or higher cut-off who de-escalate trastuzumab duration and chemotherapy dose are at least not exposed to an excess risk of death.”

SOURCE:

The study, led by Maria Vittoria Dieci, MD, University of Padova, Italy, was published online in JAMA Oncology.

LIMITATIONS:

The exploratory nature of the analysis was a key limitation because it was not prespecified in the protocol.

DISCLOSURES:

The study received support from the Italian Association for Cancer Research; University of Padova’s Department of Surgery, Oncology and Gastroenterology; Veneto Institute of Oncology; and Agenzia Italiana del Farmaco. Several authors reported receiving grants or personal fees or having other ties with various sources.

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