In an analysis from the ShortHER trial reported in JAMA Oncology, Dieci et al identified 10-year outcomes with 9 weeks or 1 year of adjuvant trastuzumab plus chemotherapy according to level of tumor-infiltrating lymphocytes (TILs) in patients with early HER2-positive breast cancer.
Study Details
Patients received four cycles of adjuvant anthracycline-based chemotherapy followed by four courses of taxanes combined with trastuzumab for 1 year (long treatment) or three courses of taxanes combined with trastuzumab for 9 weeks followed by reduced-dose anthracycline-based chemotherapy for three courses (short treatment). Tumor samples were evaluated for TILs.
Key Findings
Among the 1,253 women enrolled in the ShortHER trial, 866 women were evaluable for TILs.
Investigators reported that each 5% TIL increment was associated with improvement in distant disease–free survival (hazard ratio [HR] = 0.87, 95% confidence interval [CI] = 0.80–0.95, P = .001) and overall survival (HR = 0.89, 95% CI = 0.81–0.98, P = .01).
The 10-year overall survival rates were 91.3% among patients with TILs ≥ 20%, 93.3% among those with TILs ≥ 30%, and 98.1% among those with TILs ≥ 50%.
Patients with TILs < 20% had better 10-year distant disease–free survival with long vs short treatment (88.7% vs 81.0%), whereas patients with TILs ≥ 20% had better outcome with short vs long treatment (92.2% vs 87.1%; P for interaction = .01). Patients with TILs ≥ 20% had better 10-year overall survival with short vs long treatment (93.1% vs 89.3%, HR = 0.36, 95% CI = 0.10–1.36) and patients with TILs < 20% had better overall survival with long vs short treatment (91.3% vs 86.9%, HR = 1.36, 95% CI = 0.82–2.23; P for interaction = .06).
Conclusion
The investigators concluded: “This follow-up analysis of the ShortHER randomized clinical trial is, to our knowledge, the first demonstration of an independent effect of TILs in terms of [overall survival] for patients with …HER2-positive early breast cancer treated with adjuvant chemotherapy and anti-HER2 therapy. Patients with TILs 20% or higher who de-escalated trastuzumab duration and chemotherapy dose were not exposed to an excess risk of distant relapse or death.”
MariaVittoria Dieci, MD, Department of Surgery, Oncology and Gastroenterology, University of Padova, Italy, is the corresponding author for the JAMA Oncology article.
Disclosures: The study was supported by Agenzia Italiana del Farmaco, Italian Association for Cancer Research, and others. For full disclosures of all study authors, visit jamanetwork.com.
