27P - Tumor infiltrating lymphocytes in HER2-positive breast cancer patients treated with neoadjuvant chemotherapy plus trastuzumab, lapatinib or their c...

Date 04 May 2017
Event IMPAKT 2017
Session Welcome reception and Poster Walk
Topics Biomarkers
Breast Cancer
Translational Research
Presenter Cinzia Solinas
Authors C. Solinas1, M. Ceppi2, M. Lambertini3, M. Scartozzi4, S. Garaud5, D. Fumagalli6, E. De Azambuja7, R. Salgado8, K. Willard-Gallo5, M. Ignatiadis9
  • 1Molecular Immunology Unit, Université Libre De Bruxelles, Institut Jules Bordet, 1000 - Bruxelles/BE
  • 2Unit Of Clinical Epidemiology, IRCCS AOU San Martino-IST, Genova/IT
  • 3Breast Cancer Translational Research Laboratory, Institut Jules Bordet, Université Libre de Bruxelles, 1000 - Bruxelles/BE
  • 4Medical Oncology, University of Cagliari, Cagliari/IT
  • 5Molecular Immunology Unit, Institut Jules Bordet, 1000 - Bruxelles/BE
  • 6Breast International Group, Breast International Group, 1000 - Bruxelles/BE
  • 7Brreast Data Centre, Institut Jules Bordet, Université Libre de Bruxelles, 1000 - Bruxelles/BE
  • 8Department Of Pathology, GZA Ziekenhuizen, Sint-Augustinus campus, Wilrijk/BE
  • 9Academic Trials Promoting Unit, Institut Jules Bordet, Université Libre de Bruxelles, 1000 - Bruxelles/BE

Abstract

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To investigate the association between tumor infiltrating lymphocytes (TIL) and pathologic complete response (pCR) in HER2-positive breast cancer (BC) patients treated with neoadjuvant chemotherapy (CT) plus trastuzumab (T), lapatinib (L) or their combination (TL). A literature search encompassing PubMed, Embase and the Cochrane library through October 31, 2016 was conducted to identify randomized controlled trials (RCT) investigating neoadjuvant CT plus T, L or TL in HER2-positive BC with available information on pCR based on pre-treatment levels of TIL. Two groups were considered: high baseline TIL vs no high TIL, according to study definition. Summary risk estimates (odds ratio, OR) and 95% confidence intervals (CI) were calculated for pCR using TIL levels for each trial. Pooled analysis was conducted using the random and fixed effects models. Interaction p-value was computed using a Monte Carlo permutation test. Five RCT (CherLOB, GeparQuattro, GeparQuinto, GeparSixto and NeoALTTO) including 1,256 patients were eligible for this analysis. All studies except for NeoALTTO used a 60% cut-off for definition of high TIL subgroup (30% in NeoALTTO), and anthracycline- and taxane-based neoadjuvant CT (taxanes alone in NeoALTTO). Overall, including all the five RCT, the high TIL subgroup was associated with a significant increased pCR rate (OR 2.46; 95% CI 1.36-4.43; p=0.003). No interaction was observed between TIL subgroup (high vs other) and response to anti-HER2 agent(s) (T vs L vs TL) (p=0.747), and CT (anthracycline and taxanes vs taxanes only; p=0.201). When examining only the four RCT using neoadjuvant anthracycline- and taxane-based CT and the 60% cut-off for high TIL (n=869, NeoALTTO excluded), a stronger significant association between high TIL subgroup and pCR rate was observed (OR 2.88; 95% CI, 2.03-4.08; p<0.001). In HER2-positive BC, TIL have a strong prognostic effect; patients with >60% TIL in pre-treatment biopsy show an increased benefit from neoadjuvant anthracycline- and taxane-based CT in conjunction with anti-HER2 therapy.

Clinical trial identification