ESR1 mutations are frequent in newly diagnosed metastatic and loco-regional recurrence of endocrine-treated breast cancer and carry worse prognosis.
Background: Emerging mutations in the ESR1 gene that encodes for the estrogen receptor (ER) are associated with resistance to endocrine therapy. ESR1 mutations rarely exist in primary tumors (~ 1%) but are relatively common (10-50%) in metastatic, endocrine therapy-resistant cancers and are associat...
| Publicado en: | Breast Cancer Research Vol. 22; no. 1; pp. 1 - 12 |
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| Autores principales: | , , , , , , , , , , , , , , , , |
| Formato: | research Journal Article |
| Publicado: |
BioMed Central
2/3/2020
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=141530857&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 141530857 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 14655411 8UYJ jtl: Breast Cancer Research issn: 14655411 maglogo: N pubinfo: dt: 2/3/2020 vid: 22 iid: 1 pid: 24147 pub: BioMed Central artinfo: ui: 141530857 141530857 NLM32014063 141530857 10.1186/s13058-020-1246-5 NLM32014063 141530857 ppf: 1 ppct: 11 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: ESR1 mutations are frequent in newly diagnosed metastatic and loco-regional recurrence of endocrine-treated breast cancer and carry worse prognosis. aug: au: Zundelevich, Adi Dadiani, Maya Kahana-Edwin, Smadar Itay, Amit Sella, Tal Gadot, Moran Cesarkas, Karen Farage-Barhom, Sarit Saar, Efrat Glick Eyal, Eran Kol, Nitzan Pavlovski, Anya Balint-Lahat, Nora Dick-Necula, Daniela Barshack, Iris Kaufman, Bella Gal-Yam, Einav Nili affil: Cancer Research Center, Sheba Medical Center, Tel-Hashomer, Israel sug: subj: Antineoplastic Agents, Hormonal Pharmacodynamics Breast Neoplasms Mortality Neoplasms, Hormone-Dependent Mortality Drug Resistance, Neoplasm Proteins Mutation Neoplasm Recurrence, Local Mortality Aged Adult Treatment Outcomes Breast Neoplasms Pathology Middle Age Breast Neoplasms Drug Therapy Neoplasms, Hormone-Dependent Pathology Aged, 80 and Over Neoplasms, Hormone-Dependent Drug Therapy Neoplasm Recurrence, Local Pathology Neoplasm Recurrence, Local Breast Neoplasms Neoplasm Metastasis Female Neoplasm Recurrence, Local Drug Therapy Neoplasms, Hormone-Dependent Human Survival Validation Studies Comparative Studies Evaluation Research Multicenter Studies Scales Aged: 65+ years Adult: 19-44 years Middle Aged: 45-64 years Aged, 80 & over Female ab: Background: Emerging mutations in the ESR1 gene that encodes for the estrogen receptor (ER) are associated with resistance to endocrine therapy. ESR1 mutations rarely exist in primary tumors (~ 1%) but are relatively common (10-50%) in metastatic, endocrine therapy-resistant cancers and are associated with a shorter progression-free survival. Little is known about the incidence and clinical implication of these mutations in early recurrence events, such as local recurrences or newly diagnosed metastatic disease.Methods: We collected 130 archival tumor samples from 103 breast cancer patients treated with endocrine therapy prior to their local/metastatic recurrence. The cohort consisted of 41 patients having at least 1 sample from local/loco-regional recurrence and 62 patients with metastatic disease (of whom 41 newly diagnosed and 28 with advanced disease). The 5 most common ESR1 hotspot mutations (D538G, L536R, Y537S/N/C) were analyzed either by targeted sequencing or by droplet digital PCR. Progression-free survival (PFS), disease-free survival (DFS), and distant recurrence-free survival (DRFS) were statistically tested by Kaplan-Meier analysis.Results: The prevalence of ESR1 mutations was 5/41 (12%) in newly diagnosed metastatic patients and 5/28 (18%) for advanced metastases, detected at allele frequency > 1%. All mutations in advanced metastases were detected in patients previously treated with both tamoxifen (TAM) and aromatase inhibitors (AI). However, in newly diagnosed metastatic patients, 4/5 mutations occurred in patients treated with TAM alone. PFS on AI treatment in metastatic patients was significantly shorter for ESR1 mutation carriers (p = 0.017). In the local recurrence cohort, ESR1 mutations were identified in 15/41 (36%) patients but only 4/41 (10%) were detected at allele frequency > 1%. Again, most mutations (3/4) were detected under TAM monotherapy. Notably, 1 patient developed ESR1 mutation while on neoadjuvant endocrine therapy. DFS and DRFS were significantly shorter (p = 0.04 and p = 0.017, respectively) in patients that had ESR1 mutations (> 1%) in their loco-regional recurrence tumor.Conclusions: Clinically relevant ESR1 mutations are prevalent in newly diagnosed metastatic and local recurrence of endocrine-treated breast cancer. Since local recurrences are amenable to curative therapy, these mutations may inform the selection of subsequent endocrine therapies. pubtype: Academic Journal doctype: research Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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