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Dynamic evaluation of the immune infiltrate and immune function genes as predictive markers for neoadjuvant chemotherapy in hormone receptor positive, HER2 negative breast cancer
Department of Oncology, Karolinska Institutet and University Hospital, Stockholm, Sweden.
Department of Oncology, Karolinska Institutet and University Hospital, Stockholm, Sweden.
Department of Clinical Pathology and Cytology, Central Hospital Karlstad, Karlstad, Sweden.
Department of Clinical Pathology and Cytology, Central Hospital Karlstad, Karlstad, Sweden.
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2018 (English)In: Oncoimmunology, ISSN 2162-4011, E-ISSN 2162-402X, Vol. 7, no 9, article id e1466017Article in journal (Refereed) Published
Abstract [en]

Gene expression (GE) signatures and Tumor Infiltrating Lymphocytes (TIL) enumeration are predictive for response to neoadjuvant chemotherapy in HR- and in HER2+ breast cancer, but data are conflicting in HR+/HER2- disease. This study aimed to explore their predictive value in this subset, measured both at baseline and after short exposure to chemotherapy. Specifically, 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 and enumeration of TIL, FOXP3+ T-cells and CD163+ macrophages. An immune related gene module and the quantification of the immune infiltrate were analyzed for association with pathologic complete response (pCR), decrease in tumor size and disease-free survival (DFS). Of the 150 patients enrolled in PROMIX, 113 were HR+/HER2-. Baseline GE and immune cell enumeration data were available from 71 patients, while data after 2 cycles of chemotherapy were available from 41. At baseline, only GE was statistically significantly associated with higher pCR rates (OR 2.29, 95% CI 1.05 - 5.38, p = 0.037) and decrease in tumor size (r = 0.25, p = 0.047). In contrast, longitudinal data indicate that both GE (r = 0.54, p<0.001) and TIL abundance (p = 0.009) are stronger predictors for the reduction of tumor size, while low FOXP3+ was statistically significantly associated with an improved DFS (p = 0.027). In conclusion, GE analysis, TIL and FOXP3+ enumeration after short-term exposure to chemotherapy carry important predictive information in HR+/HER2- breast cancer at the neoadjuvant setting.

Place, publisher, year, edition, pages
Taylor & Francis, 2018. Vol. 7, no 9, article id e1466017
Keywords [en]
biomarker, breast cancer, gene expression, predictive, tumor infiltrating lymphocytes
National Category
Cancer and Oncology Immunology in the medical area
Identifiers
URN: urn:nbn:se:oru:diva-69011DOI: 10.1080/2162402X.2018.1466017ISI: 000443993100004PubMedID: 30228933Scopus ID: 2-s2.0-85050943278OAI: oai:DiVA.org:oru-69011DiVA, id: diva2:1250817
Funder
Swedish Cancer Society, CAN 2015/713Stockholm County CouncilBioCARE - Biomarkers in Cancer Medicine Improving Health Care Education and Innovation
Note

Funding Agencies:

European Society for Medical Oncology Georges Mathe Translational Research Fellowship  

Hellenic Society of Medical Oncology 

Cancer Society in Stockholm  154132 

Breast Cancer Theme Center (BRECT) at Karolinska Institutet

Roche Sweden AB  

Available from: 2018-09-25 Created: 2018-09-25 Last updated: 2018-09-25Bibliographically approved

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Erlandsson, Ann

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