Ignatiadis M, et al. - Researchers wanted to recognize biomarkers that can prognosticate outcomes in human epidermal growth factor receptor 2 (HER2)–amplified early breast cancer treated with trastuzumab/pertuzumab-based chemotherapy. They concluded that baseline tumor-infiltrating lymphocytes (TILs) percentage provided independent prognostic data in those treated with trastuzumab/pertuzumab-based neoadjuvant chemotherapy.

Methods

• In the Tryphaena trial, they determined the percentage of tumor-infiltrating lymphocytes (TILs) at baseline in 213 candidates, of which 126 showed a pathological complete response (pCR; ypT0/is ypN0), with 28 demonstrating event-free survival (EFS) effects out of 225 subjects who were randomly assigned to trastuzumab/pertuzumab concurrently or sequentially with an anthracycline-containing treatment or concurrently with an anthracycline-free therapy.
• After adjusting for clinicopathological features using logistic and Cox regression models, respectively, they evaluated links between baseline TIL percentage and either pCR or EFS.
• They assessed the associations between baseline TILs and baseline tumor gene expression data (800 gene set by NanoString) in a subset of 173 candidates to understand TIL biology.
• All statistical tests performed were two-sided.

Results

• They observed the median level of 14.1% (interquartile range = 7.1%–32.4%) among the cases with measurable TILs at baseline.
• After adjusting for clinicopathological characteristics, they did not find any relationship between baseline percentage TIL and pCR (adjusted odds ratio [aOR] for every 10-percentage unit increase in TILs = 1.12, 95% confidence interval [CI] = 0.95 to 1.31, P=.17).
• At a median follow-up of 4.7 years, they noticed a 25% reduction in the hazard for an EFS event (aOR = 0.75, 95% CI = 0.56 to 1.00, P=.05) after adjusting for baseline clinicopathological characteristics and pCR for every increase in baseline TILs of 10%.
• In addition, they recorded an inverse relationship between genes related to epithelial-mesenchymal transition, angiogenesis, and T-cell inhibition such as SNAIL1, ZEB1, NOTCH3, and B7-H3 and percentage TIL.