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Thyroid hormone receptor alpha (TRa) tissue expression in ductal invasive breast cancer: A study combining
P Charalampoudis1, G Agrogiannis2, K Kontzoglou3
1Breast Unit, Second Propedeutic Department of Surgery, Laiko Hospital, Athens University School of Medicine, Athens, Greece; Breast Unit, Guy's and Saint Thomas' NHS Foundation Trust, London, United Kingdom; Division of Cancer Studies, King's College London, United Kingdom.
Background:
In breast cancer, hormonal receptors hold promise for developing novel targeted therapies. The thyroid exerts its actions via the thyroid hormone receptors alpha and beta. The clinical significance of the expression of thyroid hormone receptors in breast cancer is unclear.
Material And Methods:
We studied thyroid hormone receptor alpha (TRa) expression in 82 samples from 41 women with ductal invasive breast cancer and no thyroid disease. We performed quantitative immunohistochemistry with digital image analysis and correlated TRa expression with clinicopathological parameters.
Results:
TRa was expressed in both normal breast epithelium and breast cancer, but expression in breast cancer was significantly lower. TRa was expressed significantly less in larger and grade III tumors. Conversely, breast cancers with lymphovascular invasion showed increased TRa expression compared to cancers without lymphovascular invasion. TRa expression was not significantly different between node-positive and node-negative breast cancers, or among different hormonal profiles and intrinsic subtypes.
Discussion:
This is the first-in-human study to combine quantitative immunohistochemistry with image analysis to study TRa expression in women with ductal invasive breast cancer and no clinical or biochemical evidence of thyroid dysfunction. We confirm that TRa is expressed in both normal and malignant breast epithelium and suggest that TRa expression is downregulated during breast carcinogenesis. Larger and higher grade breast cancers demonstrate partial loss in TRa expression. Alterations in TRa expression take place even in the absence of clinical or biochemical thyroid disease. The underlying mechanism of these findings and their potential significance in survival and relapse mandate further research.
Insights
Thyroid hormone receptor alpha (TRa) is expressed in breast cancer, but its levels decrease with larger, higher-grade tumors. This downregulation occurs even without thyroid disease, suggesting a role in breast carcinogenesis.
Area of Science:
- Oncology
- Endocrinology
- Molecular Biology
Background:
- Hormonal receptors are key targets for breast cancer therapies.
- Thyroid hormone receptors (TRa and TRb) mediate thyroid hormone actions.
- The role of TRa in breast cancer remains largely unknown.
Purpose of the Study:
- To investigate thyroid hormone receptor alpha (TRa) expression in invasive ductal breast cancer.
- To correlate TRa expression with clinicopathological features in patients without thyroid disease.
Main Methods:
- Quantitative immunohistochemistry and digital image analysis were used.
- TRa expression was assessed in 82 breast cancer samples from 41 women.
- Expression levels were correlated with tumor size, grade, lymphovascular invasion, nodal status, and molecular subtypes.
Main Results:
- TRa was present in normal breast epithelium and invasive breast cancer, but significantly lower in tumors.
- Reduced TRa expression correlated with larger tumor size and higher tumor grade (Grade III).
- Increased TRa expression was observed in cancers with lymphovascular invasion.
Conclusions:
- TRa is downregulated during breast cancer development.
- Loss of TRa expression is associated with aggressive tumor features like size and grade.
- TRa alterations occur independently of clinical thyroid dysfunction, warranting further investigation into their clinical significance for patient outcomes.
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