Cell receptors are special proteins found within and on the surface of certain cells that enable signals in the form of substances in the bloodstream to affect cell function. When a substance binds to the specific receptor designed to recognize it, the receptor will be activated, and a chain of events initiated to achieve the desired effect.
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Cells in healthy breast tissue have receptors specific for estrogen on their surface. By attaching to these estrogen receptors, estrogen can regulate the growth and function of breast cells. The majority of breast cancer cells also express the estrogen receptor, but in these cells regulation of the receptor has failed and it becomes overactive.
The presence or absence of specific receptors on the surface of cancer cells determines how they behave and can help oncologists predict the likely prognosis of a patient with breast cancer and how well the tumor will respond to a particular treatment.
Breast cancers are therefore commonly described according to the receptors they present. A breast cancer cell displaying estrogen receptors is referred to as ER+, whereas the absence of these receptors will result in the cancer being categorized as ER‑. Similar classifiers are added for several other receptor types, including progesterone (PR) and human epidermal growth factor receptor (HER),
The receptor status of a tumor may change during the course of the disease; cancer cells that are hormone-receptor-positive at diagnosis can lose their receptors over time. Equally, hormone-receptor-negative cancers may gain hormone receptors. It is therefore important that the receptor types present are verified regularly so treatment can be adjusted accordingly.
ER+ breast cancer
Compared with tumors that do not express estrogen receptors, ER+ breast cancers have a better differentiated morphologic appearance, and incidence rates increase with age rather than slowing after the menopause. Most importantly for the management of breast cancer is the fact that they exhibit stronger clinical responses to hormonal treatment.
For ER+ breast cancer cells, hormonal therapy can be used to interrupt the influence of hormones on the cells’ growth and overall functioning. Preventing estrogen stimulation in this way means that the cancer cells are less likely to survive.
Determining estrogen receptor status
A biopsy of the tumor is obtained and the sample evaluated for the presence of estrogen receptors using an immunohistochemical staining assay. On viewing, only the cells presenting estrogen receptors will be highlighted.
The proportion of cells that stain positive for estrogen receptors will then be determined. This may be presented as a percentage from 0% (no estrogen receptors present) to 100% (all cells have estrogen receptors) or as an Allred score.
The Allred scale runs from 0 to 8. The score is a combination of the percentage of cells that test positive for estrogen receptors and the intensity of the stain. The higher the score, the more receptors are present.
The proportion of estrogen-receptor positive cells required to achieve a classification of ER+ varies between laboratories. However, a score of 0 definitively indicates that the cancer is ER‑.
How does estrogen receptor status influence treatment decisions?
Although metastatic breast cancer is incurable, treatment to slow the growth of the tumor can significantly extend life expectancy. Endocrine therapies are often the treatment of choice due to their more favorable side effect profile. However, as the disease progresses, these will need to be augmented with chemotoxic treatments.
It is common for women with ER+ breast cancer to be recommended a type of endocrine therapy. Different therapies have different modes of actions, with some targeting estrogen while others act on the estrogen receptor. They may be used alone or in combination to maximize efficacy. The choice of treatment is selected on a patient-by-patient basis according to their particular situation and cancer type.
For example, in pre-menopausal women, the ovaries will still be producing estrogen so therapies that prevent peripheral estrogen synthesis, such as aromatase inhibitors, will be of little benefit used alone in these patients.
Even cancers with low numbers of estrogen receptors may respond to estrogen-targeted therapies. In such cases, they will be used in combination with chemotoxic agents or another targeted agent specific for a different receptor, such as PR or HER, that has a greater presence.
Summary
Breast cancer cells that express the estrogen receptor require estrogen to grow. The growth of ER+ tumors can thus be slowed by preventing the interaction of estrogen with the estrogen receptor.
In pre-menopausal patients, therapies that target the receptor are used, either alone or in combination with an agent that stops ovarian estrogen production.
In post-menopausal women estrogen is only produced from the conversion of androgens, anti-tumor efficacy may therefore be achieved by preventing such peripheral estrogen production.
As the breast cancer advances, hormonal therapies are likely to be used in combination with chemotoxic agents.
References
BreastCancer.org. How to Read Hormone Receptor Test Results. https://www.breastcancer.org/symptoms/diagnosis/hormone_status/read_results
Gruvberger S, et al. Estrogen Receptor Status in Breast Cancer Is Associated with Remarkably Distinct Gene Expression Patterns. Cancer Research 2001;61: 5979–5984.
Harvey JM, et al. Estrogen Receptor Status by Immunohistochemistry Is Superior to the Ligand-Binding Assay for Predicting Response to Adjuvant Endocrine Therapy in Breast Cancer. J Clin Oncol 1999:17:147‑-1481.
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