Abstract P4-01-15: Theprevalence of estrogen receptor-1 mutation in advanced breast cancer: The estrogen receptor one study (EROS)
Authors: O Najim, M Huizing, W Tjalma
Journal: Cancer Research (2019)

Abstract Background Estrogen receptor alpha (ESRα), encoded by the estrogen receptor-1 (ESR1) gene, is expressed in approximately 70% of all breast cancers, and hormonal therapy represents a major treatment modality in ESRα-positive cancers. The most commonly used endocrine therapies inhibit ESR activity by either targeting the ESR protein itself or depriving the receptor of its ligand. Endocrine therapy has become the mainstay of prevention and treatment of ESR+ breast cancers in all stages of the disease. Furthermore, ESR status might be a strong predictor of response to endocrine therapy. About 20% of patients who present with early disease will develop resistance manifested as recurrences either during or after adjuvant endocrine treatments. While in metastatic breast cancer (MBC) patients, the resistance rate could be as high as 30%. Recent studies unveiled that these ESR1 mutations lead to constitutive activity of the ESR, meaning that the receptor is active in absence of its ligand estrogen conferring resistance against endocrine therapy. Purpose: The goal of the present study is to determine the frequency rate of ESR1 mutations in hormone-sensitive advanced breast cancer by using digital droplet PCR (ddPCR) technique. Materials and Methods This retrospective study was conducted in the Multidisciplinary Breast Clinic of the Antwerp University Hospital. The seven most common ESR1mutations (c.1138G&amp;gt;C (p. (E380Q)), c.1610A&amp;gt;G (p.(Y537C)), c.1613A&amp;gt;G (p.(p.D538G)), c.1607T&amp;gt;G (p.(L536R)), c.1387T&amp;gt;C (p.S463R)), c.16410A&amp;gt;C (p.(Y537S)), c.609T&amp;gt;A (p.(Y537N)) were assessed in available baseline plasma samples of women with hormone sensitive progressive breast cancer. Inclusion criteria for study participation were: female, age above 18 years, breast cancer, positive ESR expression, 5 years endocrine therapy of the primary disease, disease progression under endocrine therapy. ESR mutations were analyzed in cell-free DNA (cfDNA) by using ddPCR. Results In EROS study, ESR1 mutations were successfully examined in cfDNA from 21 patients with advanced breast cancer. In the current study, we reported positive ESR1 mutation in 19% of patients (4/21; 95% CI, 5%-42%). The test sensitivity was lower than the targeted value &amp;lt;0.1% in 29% of patients (6/21). No significant statistical difference in baseline clinical characteristics was observed in patients with wild-type and mutant ESR (p&amp;gt;0.05). All the patients had received AI with a variable period of good response. Adjuvant endocrine therapy for primary disease was Tamoxifen (TAM) for 57% of patients (12 of 21) of whom 8 patients had received aromatase inhibitor (AI) after two years, while 43% of patients (9 of 21) had received AI as first line adjuvant hormonal therapy. However, there was no sufficient number of samples to formally analyze the clinical impact of ESR mutation on the type of endocrine therapy. Conclusion ESR1 mutation analysis should be considered in hormone-sensitive MBC patients to improve the therapeutic strategies in controlling ESR signaling before the occurrence of wide spread disease metastasis. Key words: Estrogen receptor, Mutation, breast cancer, hormonal therapy, and metastasis. Citation Format: Najim O, Huizing M, Tjalma W. Theprevalence of estrogen receptor-1 mutation in advanced breast cancer: The estrogen receptor one study (EROS) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-01-15.