219P - Immune function and response to neoadjuvant chemotherapy in hormone receptor positive, HER2-negative breast cancer

Date 11 September 2017
Event ESMO 2017 Congress
Session Poster display session
Topics Anti-Cancer Agents & Biologic Therapy
Breast Cancer, Locally Advanced
Breast Cancer
Presenter Alexios Matikas
Citation Annals of Oncology (2017) 28 (suppl_5): v68-v73. 10.1093/annonc/mdx364
Authors A. Matikas1, J. Lövrot1, A. Ramberg2, M. Eriksson2, T. Lindsten2, T. Lekberg1, I. Hedenfalk3, N. Loman3, J. Bergh1, A. Erlandsson4, T. Hatschek1, T. Foukakis1
  • 1Oncology/pathology, Karolinska Institutet, 17176 - Stockholm/SE
  • 2Clinical Pathology And Cytology, Central Hospital Karlstad, Karlstad/SE
  • 3Oncology/pathology, Lund University, 223 81 - Lund/SE
  • 4Urology, Örebro University, Örebro/SE

Abstract

Background

Gene expression (GE) signatures and Tumor Infiltrating Lymphocyte (TILs) enumeration have shown promise as predictors of response to neoadjuvant chemotherapy in Hormone Receptor negative (HR-) and HER2+, but not in HR+/HER2- breast cancer (BC). This study aimed to explore their predictive value in HR+/HER2- BC, based on previous work from our group on the association of immune function and chemosensitivity in advanced HR+ BC.

Methods

The PROMIX phase 2 trial enrolled patients with locally advanced HER2- BC to receive six cycles of epirubicin and docetaxel, plus bevacizumab during cycles 3-6. Patients underwent tumor biopsies at baseline and after cycle 2 for GE profiling using DNA microarrays and TIL enumeration according to standard guidelines. Since pathologic complete remission (pCR) is relatively rare in HR+ BC, we also associated an immune gene module score (IMS) and TIL counts with the non-dichotomous variable of decrease in tumor size.

Results

Of the 150 enrolled patients, n = 113 were HR+. For n = 71, both TIL and GE data were available at baseline, while for n = 78 and n = 49 patients longitudinal TIL and GE data at baseline and cycle 2 were available, respectively. At baseline, on both univariate (OR = 2.29, P = 0.037) and multivariate analysis (OR = 2.35, P = 0.044) IMS was associated with pCR, while its association with tumor shrinkage was only apparent on univariate (P = 0.047) and not multivariate analysis (P = 0.061). TIL infiltration >50% (n = 9) was associated with neither pCR (OR = 1.812, P = 0.61) nor tumor shrinkage (P = 0.99). However, decreases in TIL counts in cycle 2 compared with baseline were associated with lesser decreases in tumor size (P = 0.043 for univariate and P = 0.044 for multivariate analysis).

Conclusions

Baseline immune function as assessed by GE analysis, but not TIL enumeration, and a preserved abundance of TILs after chemotherapy were predictive for chemosensitivity at the neoadjuvant setting in patients with HR+, HER2- BC.

Clinical trial identification

NCT00957125

Legal entity responsible for the study

Karolinska University Hospital

Funding

Swedish Cancer Society, BioCARE, Governmental Funding of Clinical Research within the National Health 1Service and unrestricted grants from Roche Sweden AB

Disclosure

J. Bergh: Personal fees: UpToDate. Institutional grants: AstraZeneca, Amgen, Bayer, Merck, Pfizer, Roche, Sanofi-Aventis. T. Foukakis: Personal fees: Novartis, Pfizer, Roche, UpToDate. Research institutional: Pfizer, Roche. All other authors have declared no conflicts of interest.