Tumor infiltrating lymphocytes are prognostic in triple negative breast cancer and predictive for trastuzumab benefit in early breast cancer: results from the FinHER trial

Loi, S., Michiels, S., Salgado, R., Sirtaine, N., Jose, V., Fumagalli, D., Kellokumpu-Lehtinen, P.-L., Bono, P., Kataja, V., Desmedt, C., Piccart, M. J., Loibl, S., Denkert, C., Smyth, M. J., Joensuu, H. and Sotiriou, C. (2014) Tumor infiltrating lymphocytes are prognostic in triple negative breast cancer and predictive for trastuzumab benefit in early breast cancer: results from the FinHER trial. Annals of Oncology, 25 8: 1544-1550. doi:10.1093/annonc/mdu112


Author Loi, S.
Michiels, S.
Salgado, R.
Sirtaine, N.
Jose, V.
Fumagalli, D.
Kellokumpu-Lehtinen, P.-L.
Bono, P.
Kataja, V.
Desmedt, C.
Piccart, M. J.
Loibl, S.
Denkert, C.
Smyth, M. J.
Joensuu, H.
Sotiriou, C.
Title Tumor infiltrating lymphocytes are prognostic in triple negative breast cancer and predictive for trastuzumab benefit in early breast cancer: results from the FinHER trial
Journal name Annals of Oncology   Check publisher's open access policy
ISSN 1569-8041
0923-7534
Publication date 2014-08-01
Year available 2014
Sub-type Article (original research)
DOI 10.1093/annonc/mdu112
Volume 25
Issue 8
Start page 1544
End page 1550
Total pages 7
Place of publication Oxford United Kingdom
Publisher Oxford University Press
Collection year 2015
Language eng
Formatted abstract
Background: We have previously shown the prognostic importance of tumor-infiltrating lymphocytes (TILs) in newly diagnosed triple-negative breast cancer (TNBC) using tumor samples from a large clinical trial cohort. In this study, we aimed to validate these findings and also investigate associations with trastuzumab benefit in HER2-overexpressing disease (HER2+).

Patients and methods: A prospective-retrospective study was conducted using samples from the FinHER adjuvant, phase III trial that enrolled 1010 early-stage BC patients, 778 of whom were HER2-nonamplified. Those with HER2+ disease (n = 232) were randomized to 9 weeks of trastuzumab or no trastuzumab in addition to chemotherapy. Two pathologists independently quantified stromal TILs in 935 (92.6%) available slides. The primary end point of distant disease-free survival (DDFS) and interactions with trastuzumab were studied in Cox regression models.

Results: Confirming our previous findings, in TNBC (n = 134) each 10% increase in TILs was significantly associated with decreased distant recurrence in TNBC; for DDFS the hazard ratio adjusted for clinicopathological factors: 0.77; 95% confidence interval (CI) 0.61-0.98, P=0.02. In HER2+BC(n = 209), each 10%increase in lymphocytic infiltration was significantly associated with decreased distant recurrence in patients randomized to the trastuzumab arm (DDFS Pinteraction=0.025).

Conclusions: Higher levels of TILs present at diagnosis were significantly associated with decreased distant recurrence rates in primary TNBC. These results confirm our previous data and further support that TILs should be considered as a robust prognostic factor in this BC subtype. We also report for the first time an association between higher levels of TILs and increased trastuzumab benefit in HER2+ disease. Further research into why some TN and HER2+ BCs can or cannot generate a host antitumor immune response and how trastuzumab can favorably alter the immunemicroenvironment is warranted.
Keyword Lymphocytic infiltration
Breast cancer
Prognosis
Prediction
Biomarkers trastuzumab efficacy
TILs
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
School of Medicine Publications
 
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