Estrogen Receptors & HER2/neu Receptors in Breast Cancer (a TUTORIAL from Oster Oncology)

Summary

This video provides an in-depth look at two critical receptors in breast cancer: estrogen receptors (ER) and HER2 receptors. The presenter explains how these receptors function, how estrogen and epidermal growth factors stimulate them, and their impact on cell division and survival. The video highlights the mechanisms behind cancer progression, such as increased cell proliferation, angiogenesis, and metastasis. It also explores treatment options, including tamoxifen, HER2 inhibitors, and aromatase inhibitors, along with the use of targeted therapies like Ibrance. The presentation concludes with the potential role of natural compounds in modulating receptor activity.

Takeaways

• 😀 Estrogen and HER2 receptors are key players in breast cancer pathology, particularly in ER+ and HER2+ cases.
• 😀 Estrogen in pre-menopausal women is primarily produced by the ovaries, while in post-menopausal women, fat tissue becomes the dominant source through the enzyme Aromatase.
• 😀 The HER2 receptor, part of the ErbB-2 family, is a tyrosine kinase receptor that is activated by the epidermal growth factor (EGF).
• 😀 Both estrogen and HER2 receptors can affect cell function by binding with their respective growth factors or hormones, triggering intracellular signaling pathways.
• 😀 Estrogen receptors are found both embedded in the cell membrane and free-floating in the cytosol and nucleus, offering more flexibility in activation.
• 😀 When HER2 is activated by EGF, it forms a dimer and triggers a cascade involving RAS, RAF, MEK, and MAPK, ultimately affecting gene expression and cell behavior.
• 😀 Both estrogen and HER2 receptors lead to increased gene expression, which can result in abnormal cell proliferation, angiogenesis, metastasis, and reduced apoptosis in cancer cells.
• 😀 The activation of transcription factors through these receptors leads to the promotion of survival mechanisms that drive tumor growth and cancer progression.
• 😀 Ibrance (palbociclib) is a CDK4 inhibitor that works to block excessive cell division by inhibiting the cell cycle, often used in combination with aromatase inhibitors.
• 😀 Tamoxifen blocks the estrogen receptor to prevent downstream effects of estrogen binding, while monoclonal antibodies like trastuzumab (Herceptin) block HER2 activation in HER2+ cancers.
• 😀 Aromatase inhibitors, used primarily in postmenopausal cases, reduce estrogen production in fat tissue, limiting the estrogen-driven growth of ER+ breast cancer.

Q & A

What are the two dominant receptors discussed in breast cancer in the video?

The two dominant receptors discussed are the estrogen receptors (ER) and HER2 receptors, which are crucial in breast cancer pathology, especially in ER+ and HER2+ cases.

Why is it important to understand the sources of estrogen in breast cancer?

Understanding the sources of estrogen is essential because estrogen plays a significant role in the development and progression of estrogen receptor-positive (ER+) breast cancer. These sources include the ovaries in pre-menopausal women and fat tissue, which becomes more important in post-menopausal women.

What role does the enzyme aromatase play in estrogen production?

Aromatase is an enzyme found in fat tissue that converts other hormones, such as testosterone, into estrogen, which becomes a key source of estrogen in post-menopausal women.

What is the HER2 receptor, and how does it function?

The HER2 receptor is part of the ErbB family of receptors and is a tyrosine kinase receptor. It is activated by the epidermal growth factor (EGF), which triggers a cascade of intracellular signaling events that promote cell growth and division.

How does the binding of epidermal growth factor (EGF) to HER2 receptors affect the cell?

When EGF binds to the HER2 receptor, it causes two monomers (individual HER2 receptors) to dimerize, activating a signaling cascade that eventually leads to the activation of transcription factors and gene expression, promoting cell growth, survival, and division.

What are transcription factors, and how do they relate to the estrogen and HER2 receptors?

Transcription factors are proteins that, once activated by estrogen or HER2 receptors, bind to DNA and regulate gene expression. These factors are crucial in driving cellular behaviors such as division, survival, and migration.

What types of genes are activated by the estrogen and HER2 receptor pathways?

Genes related to cell proliferation (e.g., Ki67), angiogenesis (formation of new blood vessels), metastasis (spread of cancer), and survival mechanisms (e.g., decreased apoptosis) are activated, which drive cancer growth and spread.

How do drugs like tamoxifen and Herceptin target breast cancer receptors?

Tamoxifen blocks the estrogen receptor by preventing estrogen from binding, while Herceptin (trastuzumab) is an antibody that binds to the HER2 receptor, preventing EGF from docking and initiating the downstream signaling cascade.

What is the role of aromatase inhibitors in breast cancer treatment?

Aromatase inhibitors block the enzyme aromatase, which converts testosterone into estrogen in post-menopausal women, reducing estrogen levels and slowing the growth of estrogen receptor-positive breast cancer.

How does Ibrance (palbociclib) work in treating breast cancer?

Ibrance is a CDK4 inhibitor that works by blocking the proteins responsible for driving the cell cycle, ultimately slowing down the division of cancer cells.