Estrogen Receptor-Positive Breast Cancer: The Most Common Subtype

Looking at the drivers of this cancer and how they inform treatment strategies

Breast cancer is not a single disease—it’s a diverse family of subtypes, each shaped and driven by its own unique tumor biology. The most common subtype is estrogen receptor (ER)-positive breast cancer, which accounts for about 80 percent of all cases.

Decades of research led to the identification of the estrogen hormone and the discovery of specific estrogen receptors in cells. Further studies demonstrated that estrogen works by binding to its receptor. This work laid the foundation for understanding hormone-driven cancers, particularly breast cancers fueled by estrogen. Today, thanks to pivotal research—including many studies funded by BCRF—we have effective, targeted treatments for ER-positive breast cancer that continue to improve outcomes, prevent recurrence, and overcome treatment resistance.

What is estrogen receptor-positive breast cancer?

Breast cancers are broadly classified according to their hormone receptor and HER2 protein status. Hormone receptor (HR)-positive breast cancers can be further categorized as estrogen receptor (ER)-positive and/or progesterone receptor (PR)-positive. Estrogen binds to proteins called estrogen receptors, which then causes a change in the receptor that signals to the cell to keep growing. Doctors determine whether a breast cancer is positive for hormone receptors using a process called immunohistochemistry (IHC) staining, whereby dyes are linked to antibodies that recognize and bind to hormone receptors. A tumor is considered HR positive if at least 1 percent of cells are stained, indicating they have estrogen and/or progesterone receptors. On the flip side, if less than 1 percent of cells are stained, the breast cancer is considered hormone receptor-negative.

Approximately 80 percent of all breast cancers are ER-positive, and over 50 percent of those are also positive for progesterone receptors. Hormone receptor-positive breast cancers rely on hormones to grow, and thus can be treated with hormone therapy.

How common is estrogen receptor-positive breast cancer?

ER-positive breast cancer is the most common breast cancer subtype across all major racial and ethnic groups. While ER-positive breast cancers can occur at any age, they are more common in women over 50. Over 90 percent of all male breast cancers are ER-positive.

The prevalence of ER-positive breast cancer makes ongoing BCRF-funded research and long-term treatment strategies especially important.

How does estrogen receptor-positive breast cancer develop?

While the exact causes of breast cancer developing are complex and influenced by multiple factors—including genetics, hormone exposure, and aging—an overarching risk factor for ER-positive breast cancer is long-term exposure to estrogen. This can happen if a woman had early periods, late menopause, or gave birth later in life. However, no single factor causes breast cancer.

Diagnosis and staging of estrogen receptor-positive breast cancer

Doctors diagnose ER-positive breast cancer by confirming the presence of estrogen receptors in cancer cells, primarily using immunohistochemistry on biopsy or surgical tissue samples.

Staging of ER-positive breast cancer follows the TNM system, a globally recognized method for classifying solid tumors using tumor size (T), lymph node involvement (N), and metastasis (M) to determine the stage of the cancer (stage 1 to 4). Whereas the cancer’s receptor status indicates if hormone therapy should be used, staging—in particular, distinguishing between early-stage (localized) and advanced-stage disease—helps determine if surgery, radiation, chemotherapy, or a combination should be added to hormone therapy.

How is estrogen receptor-positive breast cancer treated?

Since research has demonstrated that estrogen binding to its receptor drives the growth of some breast cancers, investigators have sought to find ways to decrease estrogen or disrupt this interaction to slow or stop breast cancer growth. The first strategy developed was hormone (or endocrine) therapy, which is now the cornerstone of treatment for ER-positive breast cancer, making receptor status critical for treatment planning. The first hormone therapy and the first targeted treatment for breast cancer was tamoxifen (Nolvadex^®), which binds to estrogen receptors in breast cancer cells, preventing estrogen from binding instead. This inhibits cell growth. Most hormone therapies for breast cancer either block estrogen from binding to its receptors or reduce the levels of estrogen in the body.

Hormone therapy for breast cancer can be used at different stages of treatment and may be combined with surgery, radiation, and/or chemotherapy. Doctors and patients work together to develop a personalized treatment plan based on tumor biology, stage, and a patient’s age and menopausal status.

In early-stage breast cancer, and to decrease the risk of the cancer returning, many patients often start hormone therapy after surgery. This is known as adjuvant therapy. Patients with locally advanced disease may start hormone therapy before surgery to shrink a tumor in order to make it easier to remove. This is known as neoadjuvant therapy. For patients with metastatic breast cancer, hormone therapy may be used to slow the growth of metastases that have spread to other parts of the body.

There are now four main types of hormone therapy for breast cancer:

• aromatase inhibitors (AIs)
• selective estrogen receptor modulators (SERMs)
• selective estrogen receptor degraders (SERDs)
• and ovarian function suppression therapy.

Aromatase inhibitors (AIs), such as anastrozole (Arimidex^®) and letrozole (Femara^®), work by blocking the enzyme aromatase from making estrogen, thereby reducing estrogen levels in the body. AIs are taken as daily pills and are usually used in postmenopausal women. They are highly effective as maintenance therapies (usually started after surgery) for ER-positive breast cancers in postmenopausal women, typically taken for 5 to 10 years to prevent recurrence. In premenopausal patients with ER-positive breast cancer that has a high risk of returning, AIs may be used in combination with ovarian function suppression after surgery.

SERMs, such as tamoxifen, bind to estrogen receptors, causing a shape change that stops estrogen from binding to its receptors in breast cancer cells. This has the net effect of blocking the signal from estrogen to these cells. While SERMs have anti-estrogen effects in breast cells, they can mimic the effects of estrogen in other tissues, including in the uterus and bones. SERMs are taken in pill form. Tamoxifen can be used to treat both premenopausal and postmenopausal women with breast cancer but is more commonly used in premenopausal women.

SERDs also work by attaching to estrogen receptors, but they bind more tightly and cause the receptors to degrade. Therefore, SERDs are useful in treating ER-positive breast cancer that has developed resistance to prior hormonal therapies, in particular resistance caused by mutations in the estrogen receptor itself (ESR1 mutations). SERDs are typically used in postmenopausal women. Fulvestrant (Faslodex^®), the first SERD approved for breast cancer treatment, is given by injection. Newer SERDs, such as elacestrant (Orserdu^®) and imlunestrant (Inluriyo^®), are taken orally. Currently, SERDs are predominantly used in patients with advanced/metastatic disease, but recent clinical trial results support the use of oral SERDs for early-stage breast cancer treatment.

BCRF investigators have played crucial roles in the development and testing of many hormone-based breast cancer treatments, including AIs, SERMs, and SERDs.

The role of ovarian function and estrogen suppression

Since the ovaries are the primary source of estrogen in premenopausal women, doctors may recommend ovarian suppression (along with tamoxifen or an AI) for those with high-risk ER-positive breast cancer.

Ovarian suppression is a type of hormone therapy for breast cancer that uses drugs or surgery to prevent the ovaries from making estrogen. Common ovarian suppression medications include goserelin (Zoladex^®) and leuprolide (Lupron^®), which are both luteinizing hormone-releasing hormone (LHRH) agonists that work by disrupting signals from the brain that direct the ovaries to produce estrogen. Eliminating ovarian function can also be done surgically by removing the ovaries (oophorectomy) or by treatment with radiation. It’s one example of how precision medicine can be tailored to a person’s biology and life stage.

The SOFT/TEXT clinical trials, supported by BCRF, have shown that among premenopausal women with ER-positive breast cancer, adding ovarian function suppression to endocrine therapy (specifically with AIs) significantly reduced long-term (15-year) recurrence rates.

Advances in research and emerging therapies

BCRF continues to be at the forefront of research into ER-positive breast cancer. Areas of active research include:

• Advancing endocrine therapy effectiveness with newer generation SERDs
• Combining hormone therapy with other known or novel targeted therapies such as CDK4/6 or PI3K inhibitors to improve outcomes
• Overcoming treatment resistance by identifying new biomarkers that can help predict the chance of developing resistance or identify the specific mechanisms involved
• Exploring ways to prevent recurrence, such as expanding the use of CDK4/6 inhibitors in the adjuvant setting for early-stage high-risk ER-positive breast cancers
• Developing other strategies for treating early-stage high-risk ER-positive breast cancer
• Monitoring real-time response to personalize treatment by assessing circulating tumor DNA levels via liquid biopsy, and adjusting treatment if necessary before progression
• Optimizing treatment by evaluating shorter chemotherapy regimens and radiation alternatives

Moving forward with knowledge, hope, and research

Compared to other breast cancer subtypes, ER-positive breast cancers grow at a slower rate and have more treatment options—two factors that contribute to better prognoses. As the most common subtype of breast cancer, ER-positive breast cancers are well studied and increasingly treatable, but continue to be an ongoing research focus.

It is important to understand that ER-positive breast cancers require long-term follow up for 10 or more years because the risk of late recurrence persists. One of the biggest issues in treatment for ER-positive breast cancer is hormone therapy resistance—when breast cancer stops responding to this treatment. Researchers, including several BCRF investigators, are actively testing new strategies to figure out why this happens and how it can be stopped. Recent positive results from clinical trials testing next-generation oral SERDs both alone and in combination with other therapies such as CDK4/6 inhibitors offer promise in overcoming treatment resistance.

These and other research advances continue to improve survival, quality of life, and long-term outcomes for patients diagnosed with ER-positive breast cancer. BCRF investigators are at the forefront of these research efforts, leading the way to better, more innovative treatment options for patients.

Support life-saving breast cancer research by donating to BCRF today.

Frequently asked questions about estrogen receptor-positive breast cancer

1. Is estrogen receptor-positive breast cancer better or worse than estrogen receptor-negative breast cancer?

Rather than being “better” or “worse,” estrogen receptor status helps guide breast cancer treatment. ER-positive breast cancers tend to grow more slowly and are often treatable with targeted hormone therapies, which can be effective for many patients. Other breast cancer subtypes may require different treatment approaches. Each diagnosis is unique, and outcomes depend on many factors, including stage, tumor biology, and response to treatment.

2. What is the prognosis for estrogen receptor-positive breast cancer?

Many people with ER-positive breast cancer have a favorable prognosis, especially when the cancer is diagnosed early. Advances in treatment and ongoing research have significantly improved long-term outcomes. However, ER-positive breast cancer can sometimes recur years after initial treatment, which is why long-term follow-up and continued research are so important.

3. How is estrogen receptor-positive breast cancer treated?

Treatment for ER-positive breast cancer often includes hormone (endocrine) therapy, which works by blocking estrogen’s ability to stimulate cancer growth, or by lowering estrogen levels in the body. Depending on the individual, treatment may also include surgery, radiation therapy, chemotherapy, or targeted therapies. Care plans are personalized based on factors such as stage, menopausal status, and overall health.

4. Are there specific foods to avoid with estrogen receptor-positive breast cancer?

There is no single diet proven to treat or prevent ER-positive breast cancer. Most experts recommend focusing on a balanced, nutritious diet that supports overall health. Patients should talk with their healthcare team before making significant dietary changes, especially during treatment. Research into the relationship between diet, hormones, and breast cancer is ongoing.

5. Why does research matter for estrogen receptor-positive breast cancer?

Continued research is essential to better understand treatment resistance, prevent recurrence, and improve quality of life for people with ER-positive breast cancer. BCRF-funded research is helping drive these advances, bringing hope to patients today and in the future.

Selected References

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Allen, E., & Doisy, E. A. (1923). An ovarian hormone: Preliminary report on its localization, extraction and partial purification. American Journal of Anatomy, 34, 133–181.

Jensen, E. V. (1958). A new look at the mechanism of estrogen action. Recent Progress in Hormone Research, 14, 387–414.

Jensen, E. V., & Jacobson, H. I. (1962). Basic guides to the mechanism of estrogen action. Recent Progress in Hormone Research, 18, 387–414.

Breast Cancer Hormone Receptor Status (n.d.). American Cancer Society. https://www.cancer.org/cancer/types/breast-cancer/understanding-a-breast-cancer-diagnosis/breast-cancer-hormone-receptor-status.html

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Kim N and Lukong KE (2025) Treating ER-positive breast cancer: a review of the current FDA-approved SERMs and SERDs and their mechanisms of action. Oncol.Rev. 19:1564642. doi: 10.3389/or.2025.1564642