Topics

Fibrotic Focus in Breast Cancer

2019-10-16 10:39:35 | BioPortfolio

Summary

Despite the ongoing refinement of current breast cancer staging, clinical outcome is still varied among patients of similar stage. Further exploration of novel prognostic factors is of great clinical value. In our earlier findings, we have demonstrated the added value of fibrotic focus (FF) in the current staging. However the precise composition in different components within FF and underlying mechanism involved remain to be determined. In fact, there is unappreciated heterogeneity in FF. All these have limited its application in clinical practice. In this proposal, a systemic evaluation on the FF features in breast cancers will be performed. We aim to further characterize FF at morphological, cellular and molecular levels as well as its collagen characteristics. Given the multiple lines of evidence showing its relationship with immune components, additional attention will be put on its interaction with immune tumor environment. Finally, we plan to develop prognostic model integrating these different FF features for a more accurate risk stratification. Accumulated evidence suggested that the significance of FF in breast cancer prognosis. Moreover, the impact of fibrotic stroma on tumor immune environment may be implicative in immunotherapy. The more complete understanding of FF is pre-requisite for its development as an applicable prognostic marker in breast cancer.

Description

Background Breast cancers exhibit a wide scope of morphologic features with demonstrated prognostic significance. These features have the advantage of easily evaluated in routine reporting; thus offering great clinical potential. In our earlier analysis, fibrotic focus (FF) was demonstrated to have added value to the current staging. FF refers to the central scar like area in an invasive tumor, and is surrounded by a highly cellular zone of infiltrating tumor cells. It is composed of fibroblasts and collagen fibers forming a radially expanding fibrosclerotic core, with an incidence of around 20%. The precise composition of the different components within FF may affect its prognostic value in breast cancer.

Cancer‐associated fibroblasts (CAF) and collagen components are the most prominent features in FF. FF with proliferative CAF was associated with higher risk of metastasis. Moreover, CAFs identified by fibroblastic markers were correlated with breast cancer recurrence. In breast cancer, different subsets of CAF by differential fibroblastic markers have been characterized recently. They were present in varying proportions in breast cancer subtypes and conferred dissimilar impact on the immune tumor microenvironment (TME). Nonetheless, the relationship of CAF subtypes and FF and whether they will affect the FF prognostic impact remain elusive. Apart from CAF, the potent influence of collagen content in cancer is increasingly appreciated. Collagen stroma can modulate immune TME by inhibiting CD8 T lymphocytes infiltration. The expression of collagen and other extracellular matrix components is prognostic in different types of cancer patients, including breast cancer. For FF, detailed analysis on the collagen content is still lacking. The distinct collagen composition and organization could also impact on the prognostic capabilities of FF. The underlying mechanisms for effects of FF are largely unknown. To date, there are very few reports of molecular analysis of breast cancers with FF. FF has been associated with increased angiogenesis, hypoxia markers expression and activation of hypoxia-inducible factor-1α pathway, and concordantly increased tumor associated macrophage (TAM) infiltration. Exploration of other key biomarkers involved in will provide additional information on FF prognostication.

In this proposal, a systemic evaluation on the FF features in breast cancers will be performed. We aim to further characterize FF at different levels in detail. Finally, we plan to develop prognostic model integrating the different FF features for a more accurate risk stratification.

Study design To characterize FF based on morphologic, structural and molecular features The different morphologic features of FF will be examined and correlated with the clinico-pathologic parameters and breast cancer subtypes. To characterize the collagen stroma, the expression of these different collagens will be determined by IHC analysis. The structural characteristics of the collagen fibers will be determined on SHG signal and/or pico-Sirius red staining. The collagen composition and structural features in cases with different FF morphological features will be compared.

For the characterization of fibroblastic components, CAF populations will be determined by IHC analysis. Based on the reported CAF phenotypes, CAF markers will be examined on the consecutive IHC slides. Co-expression of CAF markers will be evaluated using multiple IHC alignment. The relationship of CAF subpopulations on FF and collagen features as well as clinico-pathologic characteristics will be examined.

The candidates from top differential genes and pathways implicated in FF will be examined. The candidates will be prioritized also based on survey of published literatures and their biological relevance.

Hierarchical clustering analysis will be performed to classify FF based on the different features. The correlation of defined FF subsets and clinico-pathologic features will be investigated.

To determine the impact of FF in immune TME To examine the effects of FF in the immune TME, we will investigate several immune cell populations in situ simultaneously using mIHC. Patients will be clustered based on their immune cell profiles. The immune cells density, their relative ratio, immune profile and spatial relationship with tumor cells will be assessed in relation to different FF features and compare between FF and non-FF cases. The interplay of immune features and FF in prognosis will be evaluated.

To investigate the prognostic value of FF in breast cancer. Having examined the clinico-pathologic correlation of various features of FF and its relationship of tumor immune environment, their prognostic value on overall survival, recurrence and metastasis will be analyszd using the Kaplan-Meier method. Their prognostic impacts will be compared with each other using univariate Cox proportional hazards model. Their independent prognostic value will be determined by multivariate analysis together with other conventional prognostic markers. A novel predictive model will be constructed based on the independent risk factors derived from the multivariate analysis. A receiver operating characteristic (ROC) curve will be used to identify the cutoff value.

Study Design

Conditions

Breast Cancer

Intervention

Immunohistochemistry

Status

Not yet recruiting

Source

Chinese University of Hong Kong

Results (where available)

View Results

Links

Published on BioPortfolio: 2019-10-16T10:39:35-0400

Clinical Trials [5216 Associated Clinical Trials listed on BioPortfolio]

Identifying Circulating Breast Cancer Cells in Women With Metastatic Breast Cancer

RATIONALE: Studying samples of blood from patients with metastatic breast cancer in the laboratory may help doctors identify biomarkers related to breast cancer and learn more about how br...

Bicalutamide in Treating Patients With Metastatic Breast Cancer

RATIONALE: Androgens can cause the growth of breast cancer cells. Antihormone therapy, such as bicalutamide, may stop the adrenal glands from making androgens. PURPOSE: This phase II tria...

Laser Spectroscopy in Diagnosing Breast Cancer in Women With Breast Lesions

RATIONALE: Diagnostic procedures, such as laser spectroscopy, may help find and diagnose breast cancer. PURPOSE: This phase I trial is studying laser spectroscopy to see how well it works...

Gene Therapy in Treating Women With Metastatic Breast Cancer

RATIONALE: Placing the gene for interleukin-12 into breast cancer cells may help the body build an immune response to kill tumor cells. PURPOSE: This phase I trial is studying the side ef...

Apatinib in Neoadjuvant Therapy for Patients With Breast Cancer

To verify the role of apatinib in neoadjuvant therapy for breast cancer, the investigators designed a prospective, randomized, parallel-controlled phase II/III trial, to investigate the ef...

PubMed Articles [15138 Associated PubMed Articles listed on BioPortfolio]

Analytical validation of a standardized scoring protocol for Ki67 immunohistochemistry on breast cancer excision whole sections: an international multicenter collaboration.

The nuclear proliferation marker Ki67 assayed by immunohistochemistry has multiple potential uses in breast cancer, but an unacceptable level of inter-laboratory variability has hampered its clinical ...

National trends of synchronous bilateral breast cancer incidence in the United States.

Increase in breast cancer survivorship, advancements in diagnostic imaging and standardization of contralateral breast screening before breast cancer surgery have resulted in increased detection of co...

Correlation between SFRP1 expression and clinicopathological parameters in patients with triple-negative breast cancer.

Breast cancer is a heterogeneous disease with distinct molecular and clinical behavior demanding reliable biomarkers, especially in triple-negative breast cancer (TNBC). This study seeks to improve th...

A direct immunohistochemistry (IHC) method improves the intraoperative diagnosis of breast papillary lesions including breast cancer.

The goal of this study is to evaluate a novel direct immunohistochemistry staining method on frozen tissues for the intraoperative diagnosis of breast papillary lesions.

Syndecan-1 facilitates breast cancer metastasis to the brain.

Although survival rates for patients with localized breast cancer have increased, patients with metastatic breast cancer still have poor prognosis. Understanding key factors involved in promoting brea...

Medical and Biotech [MESH] Definitions

Abnormal accumulation of lymph in the arm, shoulder and breast area associated with surgical or radiation breast cancer treatments (e.g., MASTECTOMY).

Metastatic breast cancer characterized by EDEMA and ERYTHEMA of the affected breast due to LYMPHATIC METASTASIS and eventual obstruction of LYMPHATIC VESSELS by the cancer cells.

A infiltrating (invasive) breast cancer, relatively uncommon, accounting for only 5%-10% of breast tumors in most series. It is often an area of ill-defined thickening in the breast, in contrast to the dominant lump characteristic of ductal carcinoma. It is typically composed of small cells in a linear arrangement with a tendency to grow around ducts and lobules. There is likelihood of axillary nodal involvement with metastasis to meningeal and serosal surfaces. (DeVita Jr et al., Cancer: Principles & Practice of Oncology, 3d ed, p1205)

A deoxycytidine derivative and fluorouracil PRODRUG that is used as an ANTINEOPLASTIC ANTIMETABOLITE in the treatment of COLON CANCER; BREAST CANCER and GASTRIC CANCER.

Carbohydrate antigen elevated in patients with tumors of the breast, ovary, lung, and prostate as well as other disorders. The mucin is expressed normally by most glandular epithelia but shows particularly increased expression in the breast at lactation and in malignancy. It is thus an established serum marker for breast cancer.

More From BioPortfolio on "Fibrotic Focus in Breast Cancer"

Quick Search

Relevant Topics

Breast Cancer
Track and monitor developments in breast cancer research and commercial development.  Follow the tabs above to read the latest global news, research, clinical trials on breast cancer and follow companies active in the development of breast cancer tr...

Cancer
  Bladder Cancer Brain Cancer Breast Cancer Cancer Cervical Cancer Colorectal Head & Neck Cancers Hodgkin Lymphoma Leukemia Lung Cancer Melanoma Myeloma Ovarian Cancer Pancreatic Cancer ...


Searches Linking to this Trial