Estrogen – ER receptors, Progesterone – PR receptors and HER receptors are found naturally in breast tissue where they affect ‘natural’ breast tissue growth. In ER, PR and or HER positive breast cancer these receptors are found in the breast cancer cells and will affect the growth of the tumour.
The Receptors of Breast Cancer
- Human cells need a way to interact with and receive signals from substances, such as hormones, drugs, antigens, or even sunlight – this is where cell receptors come in.
- A receptor is a protein molecule situated inside a cell or on the surface of a cell to which a substance can bind, activate or block
- The activation of the receptor creates the change(s) in cell activity, such increased cell division and growth
- Some substances attach fully and create a strong biological response, such as when Estrogen attaches to an Estrogen receptor
- Other substances only attach partially creating a correspondingly weaker biological response, such as when DHEA attaches to an Estrogen receptor
- If a breast cancer is diagnosed as Estrogen/ER positive, Progesterone/PR positive or HER2 positive it is referring to the presence of these receptors in the cancer cells, which is established through a biopsy
- All 3 receptors are found quite naturally in breast tissue where they effect the ‘natural’ growth of breast tissue
- BUT in breast cancer cells they can be overexpressed leading to the increased growth of the cancer cells
- The 3 most common receptors seen in breast cancer
– ER – Estrogen receptors – ER-alpha and ER-beta
– PR – Progesterone receptors
– HER2 – Human Epidermal Growth Factor Receptor-2
- Newer science also shows that the following receptors can be involved in breast cancer, but more science is needed to fully understand their roles
– AR – Androgen receptors
– GR – Glucocorticoid receptors (Cortisol)
The Receptors
ER-receptors
- Found naturally in breast tissue
- Found in cancer cells approx. 70%-80% of the time
- There are 2 types of ER
ER-alpha
- Is a nuclear receptor, found inside the cell – bind directly to DNA regulating the expression of adjacent genes
- Is activated primarily by endogenous Estrogens
– Estrone/E1
– Estradiol/E2
- Also activated by
– Endogenous Estrogens – Estriol/E3 and Estetrol/E4
– Exogenous Estrogens – Conjugated Equine/Horse Estrogens and Bioidentical Estrogens
– Synthetic Estrogens – Ethinylestradiol, Diethylstilbestrol
– Phyto-Estrogens – Daidzein, Genistein, Miroestrol
– SERMs / Selective Estrogen Receptor Modulators – Tamoxifen, Clomifene, Raloxifene
– SERDS – Selective Estrogen Receptor Degrader – Fulvestrant
– DHEA and DHEA-S
– And 100s of other substances, under the umbrella endocrine disruptors or xenoestrogens, which attach fully or partially to the receptors, such as
– BPA
– Dioxin
– Atrazine
– Phthalates
– Perchlorate
– Fire retardants
– Lead
– Mercury
– Arsenic
– PFCs
– Organophosphate pesticides
– Glycol ethers
- Functions of this receptor
– Increases cell proliferation / growth
– Plays a role in the physiological development and function of many organ systems, including the reproductive, central nervous, skeletal, and cardiovascular systems.
ER-beta
- Is a nuclear receptor, found inside the cell – bind directly to DNA regulating the expression of adjacent genes
- Is primarily activated by endogenous Estrogens
– Estradiol/E2
– Estriol/E3
- Also activated by
– Endogenous Estrogens – Estrone/E1 and Estetrol/E4
– Exogenous Estrogens – Conjugated Equine/Horse Estrogens and Bioidentical Estrogens
– Synthetic Estrogens – Ethinylestradiol, Diethylstilbestrol
– Phyto-Estrogens – Daidzein, Genistein, Miroestrol
– SERMS – Selective Estrogen Receptor Modulators – Tamoxifen, Raloxifene
– SERDS – Selective Estrogen Receptor Degrader – Fulvestrant
– DHEA and DHEA-S
– And many other molecules, under the umbrella endocrine disruptors or xenoestrogens, which attach fully or partially to the receptors, such as
– BPA
– Dioxin
– Atrazine
– Phthalates
– Perchlorate
– Fire retardants
– Lead
– Mercury
– Arsenic
– PFCs
– Organophosphate pesticides
– Glycol ethers
- Functions of this receptor
– Inhibit cell proliferation
– Oppose the actions of ER-αlpha
– A potent tumour suppressor
– Plays a crucial tumour supressing role in many cancer types, such as prostate cancer and ovarian cancer
– Is non-mammotrophic – doesn’t increase breast tissue growth
– Is highly expressed in normal breast tissue, although its expression declines with cancer progression.
– Regulates plaque formation in the brain and thereby decreases the risk of Alzheimer’s Dementia
– Can dictate both synaptic strength and neuroplasticity in the brain, particularly in the Hippocampus
NB! – Endogenous Estrogens do not cause breast cancer, but will feed it
PR Receptors
- Found naturally in breast tissue
- Is a nuclear receptor inside the cell – bind directly to DNA regulating the expression of adjacent genes
- It’s relevance to breast cancer is still not 100% understood and contradicting
– One study shows that it modulates Estrogen receptors – ER-αlpha action in breast cancer
- Recently identified progesterone metabolites may provide insights
– 5α-dihydroprogesterone (5αP) concentrations reflect cancer-promoting properties
– 3α-dihydroprogesterone (3αHP) concentrations reflect cancer-inhibiting properties.
- Other evidence indicates that the type of PR receptor may have both a prognostic and predictive value
- There are 2 types of PR
– PR-A – Antagonizes / blocks the effects of PR-B
– PR-B – Is the positive regulator of the effects of Progesterone
- The expression of progesterone receptors (PR) is evaluated as a prognostic factor together with ER
- PR is expressed in >50% of ER-positive breast tumours but rarely seen in ER-negative breast tumours
HER-2
- Is naturally found in breast tissue
- Is found on the cell surface – a membrane receptor
- Has no known direct activating substance
- Is activated via connections with other HER receptors
– The HER family consist of four members – HER-1, HER-2, HER-3, HER-4
- HER-2 receptors promote
– Cell proliferation / division (growth of breast tissue)
– Opposes apoptosis – cell death
- In cancer cells the HER-2 receptor can be expressed up to 100 times more than in normal cells
- Over-expression of HER-2 receptors occurs in approximately 15-30% of breast cancers.
- A mutation in the HER-2 gene causes cells in the breast to grow and divide at an uncontrolled rate, which can lead to tumour growth.
- The medication Trastuzumab aka Herceptin (a monoclonal antibody) may
– Block the HER-2 receptor and stop it increasing cell division and growth
– May signal the body’s immune system to destroy that cancer cell
– May activate the tumour suppressor p27, also known as CDKN1B which slows cell division
- BUT medication only works if HER-2, is overexpressed – may cause harm if it isn’t.
- NB! HER-2 does not cause breast cancer, but will speed up growth
What Causes Gene Mutation?
- Chromosomes and DNA strands can break
- Physical processes under cell division and separation can go wrong.
- DNA can be miscopied
- Repaired DNA may not be perfect
- Chemicals, known as ROS -reactive oxygen species, aka free radicals can also directly cause mutations.
- NB! – Be sure your diet is filled with antioxidants.
