Tumor infiltrating lymphocytes are prognostic in triple negative breast cancer and predictive for trastuzumab benefit in early breast cancer: results from the FinHER trial - PubMed (original) (raw)
Randomized Controlled Trial
. 2014 Aug;25(8):1544-50.
doi: 10.1093/annonc/mdu112. Epub 2014 Mar 7.
S Michiels 2, R Salgado 3, N Sirtaine 3, V Jose 4, D Fumagalli 4, P-L Kellokumpu-Lehtinen 5, P Bono 6, V Kataja 7, C Desmedt 4, M J Piccart 8, S Loibl 9, C Denkert 10, M J Smyth 11, H Joensuu 6, C Sotiriou 4
Affiliations
- PMID: 24608200
- DOI: 10.1093/annonc/mdu112
Free article
Randomized Controlled Trial
Tumor infiltrating lymphocytes are prognostic in triple negative breast cancer and predictive for trastuzumab benefit in early breast cancer: results from the FinHER trial
S Loi et al. Ann Oncol. 2014 Aug.
Free article
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 P interaction = 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 immune microenvironment is warranted.
Keywords: TILs; biomarkers trastuzumab efficacy; breast cancer; lymphocytic infiltration; prediction; prognosis.
© The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.
Comment in
- Immunoscoring breast cancer: TILs remember what they target.
Curigliano G, Perez EA. Curigliano G, et al. Ann Oncol. 2014 Aug;25(8):1455-6. doi: 10.1093/annonc/mdu227. Epub 2014 Jun 20. Ann Oncol. 2014. PMID: 24950980 No abstract available.
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