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

Table 11 Association of collagen features with therapy response

Association	Collagen Feature	p-value	Therapy	*Invasive/In situ***	Reference
Negative Association with Therapy Response	Ln F/B	p = 0.019	Tamoxifen	NA	[27]
	Tortuosity (1–4), Angle (1–2), and Width (1–2)	p < 0.05	Chemotherapy (Paclitaxel) + HER2-Targeted Agents (Trastuzumab/Pertuzumab)	NA	[66]
	Collagen Content	p = 0.005	Multi-therapy (Adriamycin/Cytoxan, Paclitaxel, Carboplatin, Bevacizumab)	Invasive	[47]
	Collagen Volume	p < 0.001	NA	Invasive	[65]
Positive Association with Therapy Response	F/B (1)	p = 0.0246	NACT (a taxane, an anthracycline, cyclophosphamide, etoposide, 5-fluorouracil, methotrexate, and/or platinum therapy) + Mastectomy	NA	[64]
No Association with Therapy Response	F/B (2)	NS
No Association with Therapy Response	Average fiber angle at the tumor boundary	NS

Definitions: F/B: (Higher value indicates larger fibril diameter, increased order in interfibrillar packing, and decreased fiber segmentation). Tortuosity 1: (90 th percentile tortuosity of fibers in tumor nest border). Tortuosity 2: (standard deviation of fiber tortuosity in tumor nest borders). Tortuosity 3: (mean tortuosity of fibers in tumor nest borders). Tortuosity 4: (median fiber tortuosity in densely inflamed stroma). Angle 1: (standard deviation of fiber relative-angles in bulk tumor borders). Angle 2: (proportion of fibers with high relative-angles in bulk tumor borders). Width 1: (kurtosis of fiber widths in tumor nest borders). Width 2: (skewness of fiber widths in tumor nest borders). F/B 1: (F/B in the tumor host interface of HER2+ patients, selecting pixels was based on an intensity threshold). F/B 2: (F/B in Triple-negative breast cancer patients)
Abbreviations: NA Not Available, NS Not Significant, TACS Tumor-associated collagen signature, Ln F/B Natural logarithm of the Forward-to-Backward ratio, NACT Neoadjuvant Chemotherapy

ISSN: 1465-542X