A predictive model of pathologic response based on tumor cellularity and tumor-infiltrating lymphocytes (CelTIL) in HER2-positive breast cancer treated with chemo-free dual HER2 blockade. (12th October 2017)

• Record Type: Journal Article
• Authors: Nuciforo, P; Pascual, T; Cortés, J; Llombart-Cussac, A; Fasani, R; Paré, L; Oliveira, M; Galvan, P; Martínez, N; Bermejo, B; Vidal, M; Pernas, S; López, R; Muñoz, M; Garau, I; Manso, L; Alarcón, J; Martínez, E; Rodrik-Outmezguine, V; Brase, J C; Villagrasa, P; Prat, A; Holgado, E
• Is Part Of: Annals of oncology. Volume 29:Number 1(2018)
• Page Start: 170
• Page End: 177
• Publication Date: 2017-10-12
• Subjects: tumor-infiltrating lymphocytes (TILs) -- HER2 -- breast cancer -- pathologic complete response; Oncology -- Periodicals; 616.992
• DOI: 10.1093/annonc/mdx647
• Languages: English
• ISSNs: 0923-7534

Abstract

Abstract: Background: The presence of stromal tumor-infiltrating lymphocytes (TILs) is associated with increased pathologic complete response (pCR) and improved outcomes in HER2-positive early-breast cancer (BC) treated with anti-HER2-based chemotherapy. In the absence of chemotherapy, the association of TILs with pCR following anti-HER2 therapy-only is largely unknown. Patients and methods: The PAMELA neoadjuvant trial treated 151 women with HER2-positive BC with lapatinib and trastuzumab [and hormonal therapy if hormone receptor (HR)-positive] for 18 weeks. Percentage of TILs and tumor cellularity were determined at baseline ( N = 148) and at day 15 (D15) of treatment ( N = 134). Associations of TILs and tumor cellularity with pCR in the breast were evaluated. A combined score based on tumor cellularity and TILs (CelTIL) measured at D15 was derived in PAMELA, and validated in D15 samples from 65 patients with HER2-positive disease recruited in the LPT109096 neoadjuvant trial, where anti-HER2 therapy-only was administer for 2 weeks, then standard chemotherapy was added for 24 weeks. Results: In PAMELA, baseline and D15 TILs were significantly associated with pCR in univariate analysis. In multivariable analysis, D15 TILs, but not baseline TILs, were significantly associated with pCR. At D15, TILs and tumor cellularity were found independently associated with pCR. A combined score (CelTIL) taking into account both variables was derived. CelTIL at D15 as a continuous variable was significantly associated with pCR, and patients with CelTIL-low and CelTIL-high scores had a pCR rate of 0% and 33%, respectively. In LPT109096, CelTIL at D15 was found associated with pCR both as a continuous variable and as group categories using a pre-defined cut-off (75.0% versus 33.3%). Conclusions: On-treatment TILs, but not baseline TILs, are independently associated with response following anti-HER2 therapy-only. A combined score of TILs and tumor cellularity measured at D15 provides independent predictive information upon completion of neoadjuvant anti-HER2-based therapy. Clinical trial number: NCT01973660.