Main Session
Sep 28
PQA 04 - Breast Cancer, Patient Reported Outcomes/QoL/Survivorship, Functional Radiation Medicine, Hematologic Malignancies, Palliative Care, and International/Global Oncology

2920 - Evaluating the Relationship between Breast Adiposity and Breast Cancer-Related Lymphedema

03:00pm - 04:00pm ET
Poster Hall - Exhibit Hall A
Screen: 31
POSTER

Presenter(s)

Nicole Wisener, MSc, BMSc Headshot
Nicole Wisener, MSc, BMSc - University of Ottawa, Ottawa, ON

M. Ma1, N. Wisener2,3, W. Shi4, and J. Y. Y. Kwan1,3; 1Institute of Medical Science, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada, 2University of Ottawa, Ottawa, ON, Canada, 3Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, ON, Canada, 4Research Institute, Princess Margaret Cancer Centre, Toronto, ON, Canada

Purpose/Objective(s):

Breast cancer treatments can damage the lymphatic system and cause lymphedema in about 1 in 5 of breast cancer survivors. Adiposity metrics, such as increased BMI and high adiposity breast tissue, are associated with severe lymphedema. However, there remains an inadequate understanding of the underlying biological mechanism of action. Previously, the Human Breast Cell Atlas revealed an increased gene expression of secreted frizzled-related protein 4 (SFRP4), a fibrosis-associated gene, in high adiposity breast tissue. Fibrosis can impede lymphatic flow and is a notable pathology of severe lymphedema.

The aim of this study is to investigate the potential role of SFRP4 in contributing to an increased risk of lymphedema development and severity via fibrosis. We hypothesized that high adiposity breast tissue expresses higher levels of SFRP4 protein and fibrotic-associated proteins (e.g., SPARC).

Materials/Methods:

Formalin-fixed, paraffin-embedded (FFPE) normal human breast tissue samples were retrieved and stained with SFRP4 and SPARC by immunohistochemistry. Stained FFPE slides were digitally imaged and analyzed using HALO software (v3.6.4134) to calculate percent positive staining. One-way ANOVA testing was used to compare percent positive staining of each protein in samples with higher and lower breast adiposity, as scored by the BI-RADS system. Pearson’s correlation analyses were completed to investigate the correlation between SFRP4 and SPARC expression. A p-value < 0.05 was considered statistically significant.

Results:

Twenty-five FFPE normal breast tissue samples were collected from stage I-III breast cancer patients. Tissue samples were distributed across the BI-RADS breast density categories including 4 BI-RADS A (highest adiposity), 10 BI-RADS B, 8 BI-RADS C, and 3 BI-RADS D (lowest adiposity) samples. Adiposity levels were tested for an association with stromal SFRP4 staining (p=0.0932) and stromal SPARC staining (p=0.0091). Stromal SFRP4 and SPARC staining demonstrated a strong positive correlation (r=0.7221, p<0.0001).

Conclusion:

High adiposity breast tissue demonstrates increased expression of fibrotic proteins, warranting further mechanistic investigation.