The intra-tumoural stroma in patients with breast cancer increases with age

Kiki M H Vangangelt,Esther Bastiaannet,Danielle Cohen,Rob A E M Tollenaar,Claire J H Kramer,Hein Putter,Andrew R Green,Wilma E Mesker,Emad A Rakha,Gabi W Van Pelt

doi:10.1007/s10549-019-05422-6

Abstract

PurposeThe tumour microenvironment in older patients is subject to changes. The tumour–stroma ratio (TSR) was evaluated in order to estimate the amount of intra-tumoural stroma and to evaluate the prognostic value of the TSR in older patients with breast cancer (≥ 70 years).MethodsTwo retrospective cohorts, the FOCUS study (N = 619) and the Nottingham Breast Cancer series (N = 1793), were used for assessment of the TSR on haematoxylin and eosin stained tissue slides.ResultsThe intra-tumoural stroma increases with age in the FOCUS study and the Nottingham Breast Cancer series (B 0.031, 95% CI 0.006–0.057, p = 0.016 and B 0.034, 95% CI 0.015–0.054, p < 0.001, respectively). Fifty-one per cent of the patients from the Nottingham Breast Cancer series < 40 years had a stroma-high tumour compared to 73% of the patients of ≥ 90 years from the FOCUS study. The TSR did not validate as an independent prognostic parameter in patients ≥ 70 years.ConclusionsThe intra-tumoural stroma increases with age. This might be the result of an activated tumour microenvironment. The TSR did not validate as an independent prognostic parameter in patients ≥ 70 years in contrast to young women with breast cancer as published previously.

Highlights

Breast cancer is the leading malignancy in European women [1]
The FOCUS study consisted of a population based cohort of women aged 65 years and older, who were diagnosed with breast cancer (N = 3672) between 1997 and 2004 in Comprehensive Cancer Centre Region West
1577 women included in the FOCUS study were eligible for inclusion

Summary

Introduction

Breast cancer is the leading malignancy in European women [1]. A major risk factor for breast cancer development is ageing [2].In the last decade, the tumour microenvironment has gained interest in unravelling cancer development and cancer progression, and as a source for new therapeutic targets and prognostic parameters. A major risk factor for breast cancer development is ageing [2]. Epidemiological and clinicopathological characteristics are different in older patients with breast cancer compared to their younger counterparts [4,5,6,7]. The biology of breast cancer is age dependent in which alterations in extracellular matrix and products secreted by senescent fibroblasts are thought to promote late-onset breast tumourigenesis; the extent is still unknown [8]. Research into the molecular profile of older patients with triple negative breast cancer showed a different stromal microenvironment favourable for tumourigenesis, in which senescence-associated secretory profile and autophagy are important aberrant stromal features induced with increasing age [9]

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