Dear Healthcare Professional,

Up to 40% of patients with ER+/HER2- mBC may acquire an ESR1 mutation during treatment with a ET + CDK4/6i. ESR1 mutations may result in faster disease progression and poorer outcomes in patients.^1,2 ESR1 mutations develop differently from other clinically relevant mutations in ER+/HER2- mBC. While mutations such as AKT, PIK3CA, and PTEN are often present at diagnosis and occur independently from prescribed treatments, ESR1 mutations emerge during treatment with ET.^2-7

Test for ESR1 mutation upon 1L progression to inform your 2L treatment decision

Abbreviations: 1L, first line; 2L, second line; AKT, protein kinase B; CDK4/6i, cyclin-dependent kinase 4/6 inhibitor; ER+, estrogen receptor-positive; ESR1, estrogen receptor 1; ESR1m, estrogen receptor 1 mutation; ET, endocrine therapy; HER2-, human epidermal growth factor receptor 2-negative; mBC, metastatic breast cancer; PIK3CA, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha; PTEN, phosphatase and tensin homolog.

References:

1. Zhang K, Hong R, Xu F, et al. Clinical value of circulating ESR1 mutations for patients with metastatic breast cancer: a meta-analysis. Cancer Manag Res. 2018;10:2573-2580. 2. Brett JO, Spring LM, Bardia A, et al. ESR1 mutation as an emerging clinical biomarker in metastatic hormone receptor-positive breast cancer. Breast Cancer Res. 2021;23(1):85.
3. Mankoo PK, Sukumar S, Karchin R. PIK3CA somatic mutations in breast cancer: mechanistic insights from Langevin dynamics simulations. Proteins. 2009;75(2):499-508. 4. Casaubon JT, Kashyap S, Regan JP. BRCA1 and BRCA2 Mutations. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2023. 5. Clatot F, Perdrix A, Beaussire L, et al. Risk of early progression according to circulating ESR1 mutation, CA-15.3 and cfDNA increases under first-line anti-aromatase treatment in metastatic breast cancer. Breast Cancer Res. 2020;22(1):56. 6. Arthur LM, Turnbull AK, Renshaw L, et al. Changes in PIK3CA mutation status are not associated with recurrence, metastatic disease or progression in endocrine-treated breast cancer. Breast Cancer Res Treat. 2014;147(1):211-219. 7. Turner NC, Oliveira M, Howell SJ, et al. Capivasertib in hormone receptor–positive advanced breast cancer. N Engl J Med. 2023;388(22):2058-2070.

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