The association between tumor-stromal collagen features and the clinical outcomes of patients with breast cancer: a systematic review

Table 7 Association of collagen features of invasive breast tumors with N stage

Association	Collagen Feature	p-value	Comparison
Positive Association with N Stage	Collagen Alignment	NA	NA	[59]
	Collagen Area	p < 0.05	NA	[59]
	COL1A1 Expression	p < 0.001	NA	[11]
	Fiber Volume	p = 0.0036	NA	[29]
	Co-relation	p = 0.0007	NA	[29]
	Collagen Content	p = 0.015	NA	[21]
	F/B ratio in Ductal Carcinoma	p < 0.05	N3 > N0-N2	[54]
	Collagen Uniformity	p = 0.034	NA	[43]
	Density	p < 0.0001	N1 > N0	[58]
	Straightness	p < 0.0001	N1 > N0	[58]
	Angular Anisotropy	p = 0.0079	NA	[57]
Negative Association with N Stage	Eccentricity, Energy	p < 0.05	NA	[29]
Negative Association with N Stage	Width, Length	p < 0.0001	N0 > N1	[58]
No Association with N Stage	F/B ratio in Lobular Carcinoma	NS	NA	[54]
	Collagen Intensity	NS	NA	[60]
	Total Collagen Deposition	NS	NA	[44]
	Local Collagen Density
	Local Collagen Alignment
	TACS-3
	TACS-2 and TACS-3
	Inter-Fiber Distance	NS	NA	[29]
	Aspect Ratio	NS	NA	[29]
	Angle	NS	N0 = N1	[58]
	Intratumoral Collagen Quantity Intratumoral Collagen Organization	NS	NA	[43]
	Collagen Area Percentage	NS	NA	[20]
	Collagen SHG Area Fraction	NS	N0 = N1	[57]
	COL1A1 Protein Expression	NS	N0=N1-N3	[10]
	COL1A1 mRNA Expression	NS	N0=N1-N3	[10]
	Collagen Content	NS	N0=N1-N3	[47]

Definitions: Intratumoral Collagen Uniformity (Higher values indicate fibers are more closely packed and evenly distributed). F/B: (Higher value indicates larger fibril diameter, increased order in interfibrillar packing, and decreased fiber segmentation). Collagen SHG area fraction (Higher values indicate a greater collagen content within the tissue). Angular Anisotropy (Higher values indicate collagen fibers are more aligned). Co-relation (Higher values indicate organized spatial patterns). Eccentricity (Higher values indicate parallel alignment). Energy (Higher values indicate homogeneous fiber distribution). Aspect Ratio (Higher values indicate more anisotropic alignment)
Abbreviations: NA Not Available, NS Not Significant, TACS Tumor-associated collagen signature, F/B the Forward-to-Backward ratio, SHG Second Harmonic Generation, COL1A1 Collagen Type I Alpha 1

ISSN: 1465-542X