Abstract
Collagen fiber organization has been found to be implicated in breast cancer prognosis. In this study, we evaluated whether computerized features of Collagen Fiber Orientation Disorder in Tumor-associated Stroma (CFOD-TS) on Hematoxylin & Eosin (H&E) slide images were prognostic of Disease Free Survival (DFS) in early stage Estrogen Receptor Positive (ER+) Invasive Breast Cancers (IBC). A Cox regression model named MCFOD-TS, was constructed using cohort St (N = 78) to predict DFS based on CFOD-TS features. The prognostic performance of MCFOD-TS was validated on cohort Sv (N = 219), a prospective clinical trial dataset (ECOG 2197). MCFOD-TS was prognostic of DFS in both St and Sv, independent of clinicopathological variables. Additionally, the molecular pathways regarding cell cycle regulation were identified as being significantly associated with MCFOD-TS derived risk scores. Our results also found that collagen fiber organization was more ordered in patients with short DFS. Our study provided a H&E image-based pipeline to derive a potential prognostic biomarker for early stage ER+ IBC without the need of special collagen staining or advanced microscopy techniques.
Highlights
Breast cancer is the second leading cause of cancer death among women in the United States, with approximately 80% of these cancers being Estrogen Receptor Positive (ER+) and 64% being early stage (Stage I & II in Tumor, Node, Metastasis staging system)[1]
We present a digital pathology-based pipeline that is able to prognosticate Disease Free Survival (DFS) in early stage ER+ Invasive Breast Cancer (IBC) by automatically quantifying the Collagen Fiber Orientation Disorder in Tumorassociated Stroma (CFOD-TS) directly from digitized routine Hematoxylin & Eosin (H&E)
Sv was considered a rigorous validation set of MCFOD-TS given that the relative homogeneity in terms of treatment regimen and cancer clinical characteristics enabled the outcome to be more reflective of the inherent aggressiveness of breast cancer
Summary
Breast cancer is the second leading cause of cancer death among women in the United States, with approximately 80% of these cancers being Estrogen Receptor Positive (ER+) and 64% being early stage (Stage I & II in Tumor, Node, Metastasis staging system)[1]. The standard treatment regimen for early stage ER+ Invasive Breast Cancer (IBC) patients is breast conserving surgery followed by hormonal therapy. While chemotherapy is able to significantly reduce the breast cancer associated mortality rate[2], most early stage ER+ IBC patients do not receive added benefit from adjuvant chemotherapy[3]. Oncotype dx (Odx)[4] is a 21-gene expression assay to assess the likelihood of cancer recurrence and the need for adjuvant chemotherapy for early stage IBC5. While the Odx test is routinely used in the clinical setting, Odx and other similar multi-gene assays tend to be timeconsuming, high-cost, tissue-destructive and are not widely available in many countries. Collagen is the most abundant ECM component in breast cancer, which provides tensile strength and structural support to the tumor tissues[10].
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
