Abstract 2362: Tumour lymphocyte infiltration has prognostic value in lymph node negative breast cancer patients with high proliferation
Authors: Jonsdottir Kristin , Egeland Nina G. , Gudlaugsson Einar , Skaland Ivar , Baak Jan P.A. , Janssen Emiel A.M. 
Published: August 2015

Abstract
Introduction: The incidence of breast cancer, and especially lymph node negative breast cancers, is increasing. Currently nearly 70% of affected women have lymph node negative cancers, and up to 90% of them receive adjuvant systemic treatment. However, only 10-20% of all node negative patients develop distant metastases without chemotherapy, and the side effects of the treatment cannot be neglected. The use of accurate and reproducible treatment-selection criteria is critical for reducing overtreatment while not increasing undertreatment. Our previous results have shown that proliferation is the strongest prognostic feature for lymph node negative breast cancer for patients under 71 years old. In addition to proliferation, this study evaluates the prognostic value of tumour infiltrating lymphocytes (TILs) and the expression pattern of miR-18a and miR-18b in lymph node negative breast cancer tissue.
Methods: Two hundred and four breast tumours were scored for degree of proliferation (Mitotic activity index (MAI), KI67 and PPH3) and TILs, both stromal (sTILs) and infiltrating TILs (iTILs). The relative amount of tumour infiltrating lymphocytes in the tumour area was then assessed as percentage of sTILs or iTILs. Furthermore, the expression of miR-18a and miR-18b was measured by qPCR in all the 204 patients and in 40 cases the expression pattern and level was measured by chromogenic in situ hybridization.
Results: Kaplan Meier curves show that patients with high proliferation (MAI≥ 10 or PPH3 ≥13) and more than a few sTIL (&gt;5%) have a 85% chance of remaining free for distant metastasis, whereas those with lower sTILs have a 62% change (p = 0.039). Chromogenic in situ hybridization with LNA-probes for miR-18a and miR-18b shows that these microRNAs are expressed in those areas with inflammation which are located within or closely surrounding the tumour. High expression of miR-18a and miR-18b is significantly associated with high proliferation, ER negativity, triple negative phenotype and cytokeratin 5 and 6 positive tumours and the presence of TILs. High expression of miR-18a or miR-18b is associated with worse prognosis for patients with a low percentage of TILs (≤5%). Cox regression analyses with traditional prognostic features and sTILs (less than 5% or &gt;5%) show that sTILs, Her2 and PPH3 are the most prognostic features in this study cohort.
Conclusion: The presence of TILs in and around a tumour has additional prognostic value in breast tumours with high proliferation. A standardized scoring method for the assessment of TILs might be a valuable biomarker for good prognosis in a patient group that otherwise has a worse prognosis and is treated with chemotherapy.
Citation Format: Kristin Jonsdottir, Nina G. Egeland, Einar Gudlaugsson, Ivar Skaland, Jan P.A. Baak, Emiel A.M. Janssen. Tumour lymphocyte infiltration has prognostic value in lymph node negative breast cancer patients with high proliferation. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2362. doi:10.1158/1538-7445.AM2015-2362