Diagnostic Accuracy of Cross-Polarization OCT and OCT-Elastography for Differentiation of Breast Cancer Subtypes: Comparative Study

Abstract

The possibility to assess molecular-biological and morphological features of particular breast cancer types can improve the precision of resection margin detection and enable accurate determining of the tumor aggressiveness, which is important for treatment selection. To enable reliable differentiation of breast-cancer subtypes and evaluation of resection margin, without performing conventional histological procedures, here we apply cross-polarization optical coherence tomography (CP-OCT) and compare it with a novel variant of compressional optical coherence elastography (C-OCE) in terms of the diagnostic accuracy (Ac) with histological verification. The study used 70 excised breast cancer specimens with different morphological structure and molecular status (Luminal A, Luminal B, Her2/Neo+, non-luminal and triple-negative cancer). Our first aim was to formulate convenient criteria of visual assessment of CP-OCT and C-OCE images intended (i) to differentiate tumorous and non-tumorous tissues and (ii) to enable more precise differentiation among different malignant states. We identified such criteria based on the presence of heterogeneities and characteristics of signal attenuation in CP-OCT images, as well as the presence of inclusions/mosaic structures combined with visually feasible assessment of several stiffness grades in C-OCE images. Secondly, we performed a blinded reader study of the Ac of C-OCE versus CP-OCT, for delineation of tumorous versus non-tumorous tissues followed by identification of breast cancer subtypes. For tumor detection, C-OCE showed higher specificity than CP-OCT (97.5% versus 93.3%) and higher Ac (96.0 versus 92.4%). For the first time, the Ac of C-OCE and CP-OCT were evaluated for differentiation between non-invasive and invasive breast cancer (90.4% and 82.5%, respectively). Furthermore, for invasive cancers, the difference between invasive but low-aggressive and highly-aggressive subtypes can be detected. For differentiation between non-tumorous tissue and low-aggressive breast-cancer subtypes, Ac was 95.7% for C-OCE and 88.1% for CP-OCT. For differentiation between non-tumorous tissue and highly-aggressive breast cancers, Ac was found to be 98.3% for C-OCE and 97.2% for CP-OCT. In all cases C-OCE showed better diagnostic parameters independently of the tumor type. These findings confirm the high potential of OCT-based examinations for rapid and accurate diagnostics during breast conservation surgery.

Keywords: breast cancer; compressional optical coherence elastography (C-OCE); cross-polarization optical coherence tomography (CP-OCT); image assessment.

Figure 1

Representative depth-wise co- and cross-polarization OCT images (a,b) of non-tumorous and tumorous breast tissue with the corresponding histology (c). (a1–c1) Adipose tissue with streaks of connective tissue; (a2–c2) fibroadenomatosis/fibroadenoma; (a3–c3) DCIS; (a4–c4) invasive ductal carcinoma (IDC) of scirrhous structure (low-aggressive breast cancer subtype); (a5–c5) IDC of solid structure (highly-aggressive breast cancer subtype). (a1–a5) OCT images in co-polarization channel; (b1–b5) OCT images in cross-polarization channel; (c1–c5) histological images, haematoxylin and eosin (H&E) staining. Abbreviations: A—adipose, CT—connective tissue, FA—fibroadenomatosis, ADH—atypical ductal hyperplasia, DCIS—ductal carcinoma in situ, TS—tumor stroma, TC—cluster of tumor cells.

Figure 2

Representative depth-wise C-OCE images (a1–a6) of non-tumorous and tumorous breast tissue with corresponding histological images (b1–b6). (a1–b1) Adipose tissue with streaks of connective tissue; (a2–b2) fibroadenomatosis/fibroadenoma; (a3–b3) DCIS; (a4,a5–b4,b5) IDC of scirrhous structure (low-aggressive breast cancer subtypes); (a6–b6) IDC of solid structure (highly-aggressive breast cancer subtype). Abbreviations: A—adipose, CT—connective tissue, ADH—atypical ductal hyperplasia, FA—fibroadenomatosis, DCIS—ductal carcinoma in situ, TS—tumor stroma, TC—cluster of tumor cells.

Figure 3

Receiver operating characteristic (ROC)-curves showing the results of visual assessment CP-OCT images for distinguishing non-tumorous breast tissue from tumor (a), DCIS from invasive breast cancer (b), low-aggressive invasive breast cancer from highly aggressive (c), non-tumorous breast tissue from low-aggressive breast cancer (d), non-tumorous breast tissue from highly aggressive breast cancer (e) for six “blinded” readers.

Figure 4

ROC-curves showing the results of visual assessment of C-OCE images for distinguishing non-tumorous from tumorous breast tissue (a), DCIS from invasive breast cancer (b), low-aggressive invasive breast cancer from highly-aggressive (c), non-tumorous breast tissue from low-aggressive breast cancer (d), non-tumorous breast tissue from highly-aggressive breast cancer (e) for six “blinded” readers.

Figure 5

Histological image (a) demonstrating transition between non-tumorous (fibrous stroma—FS) and tumorous breast tissues (low-aggressive IDC of scirrhous structure); (b) is the corresponding CP-OCT image in the cross-polarization channel and (c) is the C-OCE images of the same area. HS denotes hyalinized stroma, and TC—clusters of tumor cells.