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ESR1 MUTATIONS IN a/mBC

What are estrogen receptor 1 (ESR1) mutations?

Estrogen receptor 1 (ESR1) mutations are resistance mutations in breast cancer cells that may cause endocrine therapy to stop working.1,2

ESR1 mutations develop in cancer cells after exposure to certain endocrine therapies (ET).2 These mutations are not inherited;3
therefore, they mainly occur in patients with a/mBC, where ET is the main standard of care.2

ESR1 mutations are rarely found in the tumor at primary diagnosis of mBC but the longer a person with mBC is exposed to ET, the higher the chance they may develop an ESR1 mutation.2,4,5

This means, even if a tumor progresses on ET but no ESR1 mutation is detected, an ESR1 mutation can still arise over the course of treatment – the chance is even higher in later treatment lines (~40%).2,4-8

Resistance to therapy

Cancers can develop ways of bypassing effective treatments, such as developing changes to genes – these are known as mutations, or genetic alterations.1

Resistance mutations may reduce the effectiveness of treatments, allowing the cancer to spread, grow, or worsen (disease progression).1

Impact of ESR1 mutations on a/mBC treatment

ESR1 mutations make the cancer more challenging to treat, causing it to spread faster.5

However, ESR1 mutations can be detected and analyzed, and serve to inform treatment decisions.1,5

ESR1 mutations play a crucial role in the management of a/mBC.1,9

Knowing the biomarker mutation status in a/mBC for genes such as ESR1, PIK3CA, AKT1 and others may inform clinical decision making by helping the healthcare team decide which treatment options are more appropriate for patients.1,9

AKT1: serine/threonine kinase 1; a/mBC: advanced/metastatic breast cancer; CDK4/6: cyclin D kinase 4/6; ESR1: estrogen receptor 1; ET: endocrine therapy; PIK3CA: phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha.

  1. Hartkopf AD, et al. Breast Care (Basel). 2020;15(4):347–54.
  2. Allouchery V, et al. Breast Cancer Res. 2018;20(1):40.
  3. National Cancer Institute. Dictionary of Cancer Terms. Somatic Mutation. Accessed March 2026. Available at: https://www.cancer.gov/publications/dictionaries/cancer-terms/def/somatic-mutation.
  4. Tolaney S, et al. J Clin Oncol. 2023;41(24):4014–24.
  5. Brett JO, et al. Breast Cancer Res. 2021;23(1):85.
  6. Bhave MA, et al. Breast Cancer Res Treat. 2024;207(3):599–609.
  7. Bidard FC, et al. J Clin Oncol. 2022;40(28):3246–56.
  8. Schiavon G, et al. Sci Transl Med. 2015;7(313):313ra182.
  9. Neves Rebello Alves L, et al. Genes (Basel). 2023;14(7):1364.