The relationship between the tumour stroma percentage, clinicopathological characteristics and outcome in patients with operable ductal breast cancer

Abstract

Background:The percentage of tumour stroma (TSP) has recently been reported to be a novel independent predictor of outcome in patients with a variety of common solid organ tumours. The aim of this study was to examine the relationship between TSP, clinicopathological characteristics and outcome in patients with invasive ductal breast cancer, in particular node negative and triple negative disease.Methods:A total of 361 patients with primary operable invasive ductal breast cancer were included in this study. The TSP was assessed visually on the haematoxylin and eosin-stained tissue sections. With a cutoff value of 50% TSP, patients with ⩽50% stroma were classified as the low-TSP group and those with >50% stroma were classified as the high-TSP group.Results:A total of 109 (30%) patients had high TSP. Patients with high TSP were old age (P=0.035), had more Her-2-positive tumours (P=0.029), low-grade tumour inflammatory infiltrate (P=0.034), low CD68+macrophage infiltrate (P<0.001), low CD4+ (P=0.023) and low CD8+ T-lymphocytes infiltrate (P=0.017), tumour recurrence (P=0.015) and shorter cancer-specific survival (P<0.001). In node-negative patients (n=207), high TSP was associated with low CD68+macrophage infiltrate (P=0.001), low CD4+ (P=0.040) and low CD8+ T-lymphocytes infiltrate (P=0.016) and shorter cancer-specific survival (P=0.005). In triple negative patients (n=151), high TSP was associated with high tumour grade (P=<0.001), lymph node positivity (P=0.027), low CD68+macrophage infiltrate (P=0.011) and shorter cancer-specific survival (P=0.035). The 15-year cancer-specific survival rate was 79% vs 21% in the low-TSP group vs high-TSP group. In multivariate survival analysis, a high TSP was associated with reduced cancer-specific survival in the whole cohort (P=0.001), node-negative patients (P=0.007) and those who received systemic adjuvant therapy (P=0.021), independent of other pathological characteristics including host inflammatory response. However, TSP was not an independent prognostic factor for triple negative patients (P=0.151).Conclusions:A high TSP in primary operable invasive ductal breast cancer was associated with recurrence and poorer long-term survival. The inverse relation with the tumour inflammatory infiltrate highlights the importance of the amount of tumour stroma on immunological response in patients with primary operable ductal breast cancer. Implementing this simple and reproducible parameter in routine pathological examination may help optimise risk stratification in patients with invasive ductal breast cancer.

Tertiary lymphoid structures: prognostic significance and relationship with tumour-infiltrating lymphocytes in triple-negative breast cancer

“…The prognostic significance of tumour stroma has been reported in breast cancer 13–16. Gujam et al 16 also showed a correlation between a high percentage (>50%) of tumour stroma and low-grade tumour inflammatory infiltration. However, those authors only evaluated the relationship between tumour stroma and peritumoral lymphocytic infiltration without evaluation of TILs in the interior of invasive tumours.…”

“…Slides were histopathologically analysed for (i) TILs (defined as the mean percentage of stroma of invasive carcinoma infiltrated by lymphocytes and plasma cells in 10% increments; if <10% of stroma was infiltrated by TILs, 1% or 5% criteria were used; all available full sections were evaluated);1 19 (ii) the amount of inflammatory cells evaluated at the tumour's invasive margin (according to Klintrup criteria; score 0, no inflammatory cells at the invasive margin; score 1, mild and patchy increase of inflammatory cells; score 2, increased inflammatory cells forming a band-like infiltration at the invasive margin; score 3, prominent inflammatory reaction forming a cup-like zone at the invasive margin);6 20 (iii) aggregation of lymphoid cells in terminal duct lobular units (TDLUs; within 5 mm and >5 mm from the invasive or in situ carcinoma); (iv) the amount of TLSs in adjacent tissue including the in situ component (none, no TLS formation in the area adjacent to the tumour; little, TLSs occupying an area of <10% of the circumference of the tumour; moderate, 10–50%; or abundant, >50%; shown in figure 1); (v) the presence or absence of a germinal centre in TLSs; (vi) the percentage of tumour stroma in the most invasive tumour area (high percentage of tumour stroma, >50%; low percentage of tumour stroma, ≤50%);16 (vii) heterogeneity of the tumour (heterogeneous: invasive tumour mixed with normal breast parenchyma; homogeneous: invasive tumour mass without normal breast parenchyma); (viii) histological subtype and grade, percentage of in situ component, tumour size, pT stage, pN stage and lymphovascular invasion. Lymphoid aggregation with vessels showing HEV features (plump, cuboidal endothelial cells) with or without germinal centres was considered a TLS.…”

High Tumor Stroma Proportion is a Worse Prognostic Factor in Colorectal Cancer

“…In recent research, some new parameters have emerged that may have a prognostic role in colorectal cancer, one of them being the amount of stroma, which was fi rst demonstrated as a prognostic factor in breast and esophageal cancer [17][18][19][20][21][22] . Th e role of stroma proportion, or tumor cell proportion in the prognosis of colorectal cancer has been reported in four papers so far; they have demonstrated the proportion of stroma to be a signifi cant prognostic factor in colorectal cancer and the higher proportion of tumor stroma to be associated with better patient prognosis 24,25,28,29 .…”

“…It is believed that stroma induces tumorigenesis by various mechanisms such as remodeling of extracellular matrix, suppression of immune response and motility, as well as aggressiveness of cancer cells [15][16][17] . It has been evident that stroma has a prognostic value in esophageal cancer 18,19 and breast cancer 20 , especially triple negative breast cancer 21,22 . Using simple modifi ed methodology, we tried to determine the impact of stroma proportion on progression-free survival and overall survival.…”

Emboles lymphatiques des carcinomes mammaires invasifs félins : amélioration de leur détection par immunohistochimie et valeur pronostique

“…Un même ordre de fréquence est rapporté dans le carcinome canalaire invasif du sein chez la femme (moyenne pondérée de 33% en HES avec un intervalle allant de 10 à 49%) selon la méta-analyse de Gujam et al (2014b).…”