The landscape of ERBB2-positive breast cancer treatment may be poised for a significant shift, as new evidence suggests that tumor-infiltrating lymphocytes (TILs) could help identify patients who can safely receive shorter durations of trastuzumab therapy. These findings emerge from a follow-up analysis of the ShortHER randomized clinical trial, published in JAMA Oncology.
Key Trial Findings
The multicenter, phase 3 noninferiority study, conducted across Italian centers, evaluated 866 patients with early ERBB2-positive breast cancer. The analysis revealed a striking correlation between TIL levels and patient outcomes. For each 5% increase in TILs, researchers observed improved distant disease-free survival (DDFS) (HR, 0.87; 95% CI, 0.80-0.95; P = .001) and overall survival (OS) (HR, 0.89; 95% CI, 0.81-0.98; P = .01).
Particularly noteworthy was the finding that patients with TILs at or above 20% showed superior outcomes with a shorter 9-week trastuzumab regimen compared to the standard 1-year treatment. These patients achieved a 10-year DDFS of 92.2% with the shorter treatment versus 87.1% with the longer regimen.
Treatment Duration and TIL Levels
The study revealed distinct treatment response patterns based on TIL status. Patients with lower TIL levels (below 20%) demonstrated better outcomes with the traditional one-year trastuzumab treatment, achieving a 10-year DDFS of 88.7% compared to 81.0% with the shorter regimen. Overall survival trends similarly favored the shorter treatment in patients with higher TILs (93.1% vs 89.3%).
Clinical Implications and Future Directions
"This updated analysis from the ShortHER trial provides, to our knowledge, the first evidence of an independent effect of TILs on OS in patients with ERBB2-positive early breast cancer treated with adjuvant chemotherapy and trastuzumab," the researchers noted.
The findings suggest a potential paradigm shift in treatment approaches for ERBB2-positive breast cancer, which affects approximately 20% of breast cancer patients. The ability to identify patients who could safely receive shorter treatment durations could lead to reduced treatment burden and healthcare costs while maintaining efficacy.
Study Limitations
Several limitations warrant consideration. The analysis included TIL data from only 69% of the original ShortHER population, though this percentage aligns with similar studies. Additionally, the 20% TIL cut-off point was arbitrarily selected, making analyses using this threshold exploratory rather than definitive.
The researchers emphasize that validation studies are essential before implementing these findings in clinical practice. They suggest that incorporating immune-related features into prognostic tools could advance personalized treatment strategies for ERBB2-positive early breast cancer, moving beyond traditional clinical-pathological features.
