Estrogen Receptor-Positive Breast Cancer: Insights and Findings
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Estrogen Receptor-Positive (ER+) breast cancer is the most common type of breast cancer, accounting for about 70–80% of all cases [1], [4]. This form of cancer is characterized by cells that have special proteins capable of binding to the hormone estrogen. When estrogen attaches to these receptors, it promotes the growth of the tumor. Because of this connection, treatments often focus on blocking estrogen’s effects or reducing its production to slow down or stop tumor growth. ER+ breast cancer may be diagnosed early or at a more advanced stage, and thanks to significant advances in treatment, patients now have a much better chance of successful outcomes.
Table of Contents
Prevalence and Characteristics
Research that analyzed over 800,000 breast cancer cases found that around 75.1% of them tested positive for both estrogen and progesterone receptors [2]. In other words, the majority of invasive breast cancers contain cells that react to these hormones. This finding emphasizes the important role hormone receptors play in both the development and treatment of the disease [1].
Growth Response to Estrogen
The growth of ER+ breast cancer is mainly driven by estrogen-dependent signals [7], [8]. When estrogen binds to its receptors on the cancer cells, it not only encourages the tumor to grow but can also help it spread to other parts of the body. In many cases, the estrogen receptor is a key factor in making the cancer more aggressive [3]. This understanding has shaped the development of targeted therapies that disrupt these signals.
Hormone Therapy
Hormone therapy, also known as endocrine therapy (ET), is a cornerstone treatment for ER+ breast cancer at all stages [6], [9]. It works by interfering with estrogen’s role in cancer cell growth, thereby reducing the progression of the disease. The main types of hormone therapy include:
- Selective Estrogen Receptor Modulators (SERMs): Drugs such as tamoxifen block estrogen from attaching to its receptor on cancer cells. By preventing this binding, SERMs stop estrogen from stimulating cancer cell growth [4], [7].
- Aromatase Inhibitors (AIs): Medications like anastrozole and letrozole reduce the production of estrogen in the body, which is particularly effective for women who have gone through menopause [4], [7].
- Selective Estrogen Receptor Degraders (SERDs): Agents such as fulvestrant work by breaking down the estrogen receptor itself, thereby stopping estrogen from affecting the cancer cells [7], [8].
Effectiveness of Hormone Therapy
Hormone therapies have played a major role in improving survival for patients with ER+ breast cancer [1]. By blocking or reducing estrogen’s impact, these treatments slow the cancer’s growth and help lower the chance of recurrence. Additionally, hormone therapy can be used both before and after surgery, depending on the individual case.
One specific approach is Neoadjuvant Endocrine Therapy (NET), which is administered before surgery to shrink tumors. Reducing the tumor size in this way can make surgical removal easier and sometimes allows for less invasive surgery. Studies have shown that NET is as effective as chemotherapy in shrinking tumors, but it tends to have fewer side effects [5]. This means that patients may experience less discomfort during treatment, contributing to an overall better quality of life.
Challenges
Endocrine Resistance
Despite the effectiveness of hormone therapies, there is a significant challenge: sometimes the cancer cells become resistant to treatment. This resistance can occur due to mutations in the estrogen receptor gene (ESR1) or through the activation of alternative pathways that allow the cancer to continue growing even when hormone therapy is used [3]. In simple terms, the cancer finds new ways to thrive despite treatment efforts.
Emerging Treatments
Researchers are actively working on new methods to overcome endocrine resistance and improve treatment outcome. Some promising strategies include:
- Multi-Target Compounds: These drugs are designed to block several growth signals at once, which may prevent the cancer from bypassing the effects of hormone therapy.
- Next-Generation SERDs: Newer drugs in this class are being developed to break down the estrogen receptor more efficiently than current options, potentially offering better control over tumor growth [8].
- Combination Strategies: Pairing hormone therapy with other targeted drugs—such as CDK4/6 inhibitors, PI3K inhibitors, and mTOR inhibitors—has shown improved results, particularly in advanced cases. These combinations work by attacking the cancer on multiple fronts, making it harder for the tumor to develop resistance [10].
Final Thoughts
Estrogen Receptor-Positive (ER+) breast cancer is the most common form of the disease, largely due to its reliance on estrogen for growth. Treatments that block or reduce the effects of estrogen, including SERMs, AIs, and SERDs, have significantly improved survival rates. However, the challenge of endocrine resistance—where the cancer stops responding to hormone therapies—remains. This has spurred research into innovative treatment strategies such as multi-target compounds, next-generation SERDs, and combination therapies. These ongoing efforts are aimed at developing more effective future treatments to further enhance patient outcomes.
References
[1] Wei S. (2023). Hormone receptors in breast cancer: An update on the uncommon subtypes. Pathology, research and practice, 250, 154791. https://doi.org/10.1016/j.prp.2023.154791
[2] Dauphine, C., Moazzez, A., Neal, J. C., Chlebowski, R. T., & Ozao-Choy, J. (2020). Single Hormone Receptor-Positive Breast Cancers Have Distinct Characteristics and Survival. Annals of surgical oncology, 27(12), 4687–4694. https://doi.org/10.1245/s10434-020-08898-5
[3] Mouabbi, J.A., Osborne, C.K., Schiff, R. et al. Management of hormone receptor–positive, human epidermal growth factor 2–negative metastatic breast cancer. Breast Cancer Res Treat 190, 189–201 (2021). https://doi.org/10.1007/s10549-021-06383-5
[4] Lumachi, F., Brunello, A., Maruzzo, M., Basso, U., & Basso, S. M. (2013). Treatment of estrogen receptor-positive breast cancer. Current medicinal chemistry, 20(5), 596–604. https://doi.org/10.2174/092986713804999303
[5] Spring, L. M., Gupta, A., Reynolds, K. L., Gadd, M. A., Ellisen, L. W., Isakoff, S. J., Moy, B., & Bardia, A. (2016). Neoadjuvant Endocrine Therapy for Estrogen Receptor-Positive Breast Cancer: A Systematic Review and Meta-analysis. JAMA oncology, 2(11), 1477–1486. https://doi.org/10.1001/jamaoncol.2016.1897
[6] Mata, D. G. M. M., Amir Carmona, C., Eisen, A., & Trudeau, M. (2022). Appraising Adjuvant Endocrine Therapy in Hormone Receptor Positive HER2-Negative Breast Cancer-A Literature Review. Current oncology (Toronto, Ont.), 29(7), 4956–4969. https://doi.org/10.3390/curroncol29070394
[7] Haines, C. N., Wardell, S. E., & McDonnell, D. P. (2021). Current and emerging estrogen receptor-targeted therapies for the treatment of breast cancer. Essays in biochemistry, 65(6), 985–1001. https://doi.org/10.1042/EBC20200174
[8] Lloyd, M. R., Wander, S. A., Hamilton, E., Razavi, P., & Bardia, A. (2022). Next-generation selective estrogen receptor degraders and other novel endocrine therapies for management of metastatic hormone receptor-positive breast cancer: current and emerging role. Therapeutic advances in medical oncology, 14, 17588359221113694. https://doi.org/10.1177/17588359221113694
[9] Ferro, A., Campora, M., Caldara, A., De Lisi, D., Lorenzi, M., Monteverdi, S., Mihai, R., Bisio, A., Dipasquale, M., Caffo, O., & Ciribilli, Y. (2024). Novel Treatment Strategies for Hormone Receptor (HR)-Positive, HER2-Negative Metastatic Breast Cancer. Journal of Clinical Medicine, 13(12), 3611. https://doi.org/10.3390/jcm13123611
[10] Ferreira Almeida, C., Oliveira, A., João Ramos, M., Fernandes, P. A., Teixeira, N., & Amaral, C. (2020). Estrogen receptor-positive (ER+) breast cancer treatment: Are multi-target compounds the next promising approach?. Biochemical pharmacology, 177, 113989. https://doi.org/10.1016/j.bcp.2020.113989