TILs are an established prognostic factor for triple negative breast cancer. We investigated the prognostic role of TILs for HER2+ early breast cancer patients enrolled in the prospective ShortHER trial.
The ShortHER study randomized 1254 patients with HER2+ early breast cancer to receive 9 weeks vs 1 year of adjuvant trastuzumab combined with chemotherapy (Conte, ASCO 2017). TILs were assessed for 855 cases on centralized HES slides according to recommendations (Salgado, Ann Oncol 2015). Metastasis-free survival (MFS) was calculated from randomization to distant disease recurrence or death. Median follow up was 72 months.
Median TILs was 5% (Q1-Q3 1%-15%). Higher TILs were associated with hormone receptor-negative status (p < 0.001) and age <60 years (p = 0.008). There was no association with stage and PIK3CA mutation. Increased TILs were associated with better MFS (HR 0.69, 95%CI 0.54-0.88 for each 10% TILs increment, p = 0.003). 5-yrs MFS rates were 91%, 94% and 100% for TILs<20%, TILs > =20% & <50% and TILs > =50% (p = 0.013). Multivariable cox models confirmed TILs as independent prognostic factor (Table).Table: 186O
|MULTIVARIATE COX MODELS FOR MFS|
|Factors||All patients||Hormone Receptor neg||Hormone Receptor pos|
|HR (95% CI)||p||HR (95% CI)||p||HR (95% CI)||p|
|TILs 10% increase||0.67 (0.52-0.86)||0.001||0.72 (0.53-0.97)||0.031||0.57 (0.36-0.91)||0.017|
|HR pos vs neg||0.63 (0.39-1.00)||0.049||-||-||-||-|
|Stage I-II vs III||0.31 (0.20-0.50)||<0.001||0.27 (0.13-0.59)||0.001||0.33 (0.19-0.60)||<0.001|
|Age >60 vs < 60||1.02 (0.65-1.60)||0.936||1.44 (0.69-3.02)||0.337||0.82 (0.45-1.47)||0.501|
The association between 10% TILs increments and MFS was significant in the short (HR 0.49, 95%CI 0.29-0.82, p = 0.006) but not in the long arm (HR 0.84, 95%CI 0.65-1.10, p = 0.212). Patients with TILs <20% benefitted from long treatment (HR 0.76, 95%CI 0.60-0.97, p = 0.024), whereas for patients with TILs > =20% the HR favored the short arm (HR 2.79, 95%CI 0.98-7.96, p = 0.055; 8 events only). Interaction test showed p = 0.064 (arm*10% TILs increase) and p = 0.019 (arm*TILs binary variable with 20% cutoff).
TILs are an independent prognostic factor for HER2+ early breast cancer patients treated with adjuvant chemotherapy and trastuzumab. Integration of TILs in prognostic algorithms can help refining risk stratification and guiding therapeutic de-escalation.
Clinical trial identification
EudraCT 2007-004326-25 Start date: 2007-11-15.
Legal entity responsible for the study
University of Modena and Reggio Emilia; University of Padova.
Agenzia Italiana del Farmaco (AIFA).
P.F. Conte: Speaker's bureau: Roche Genentech; Research funding (Institution): Roche. V. Guarneri: Research funding (Institution): Roche. All other authors have declared no conflicts of interest.