Your browser doesn't support javascript.
loading
The estrogen receptor-alpha S118P variant does not affect breast cancer incidence or response to endocrine therapies.
Button, Berry; Croessmann, Sarah; Chu, David; Rosen, D Marc; Zabransky, Daniel J; Dalton, W Brian; Cravero, Karen; Kyker-Snowman, Kelly; Waters, Ian; Karthikeyan, Swathi; Christenson, Eric S; Donaldson, Josh; Hunter, Tasha; Dennison, Lauren; Ramin, Cody; May, Betty; Roden, Richard; Petry, Dana; Armstrong, Deborah K; Visvanathan, Kala; Park, Ben Ho.
Afiliación
  • Button B; The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Croessmann S; Vanderbilt Ingram Cancer Center, Vanderbilt Universtiy Medical Center, 2220 Pierce Avenue, PRB 777, Nashville, TN, 37232, USA.
  • Chu D; The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Rosen DM; The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Zabransky DJ; The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Dalton WB; The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Cravero K; The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Kyker-Snowman K; The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Waters I; The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Karthikeyan S; The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Christenson ES; The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Donaldson J; The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Hunter T; The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Dennison L; The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Ramin C; The Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA.
  • May B; The Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA.
  • Roden R; The Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA.
  • Petry D; The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Armstrong DK; The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Visvanathan K; The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Park BH; The Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA.
Breast Cancer Res Treat ; 174(2): 401-412, 2019 Apr.
Article en En | MEDLINE | ID: mdl-30560461
ABSTRACT

PURPOSE:

Estrogen receptor-alpha (ER) is a therapeutic target of ER-positive (ER+) breast cancers. Although ER signaling is complex, many mediators of this pathway have been identified. Specifically, phosphorylation of ER at serine 118 affects responses to estrogen and therapeutic ligands and has been correlated with clinical outcomes in ER+ breast cancer patients. We hypothesized that a newly described germline variant (S118P) at this residue would drive cellular changes consistent with breast cancer development and/or hormone resistance.

METHODS:

Isogenic human breast epithelial cell line models harboring ER S118P were developed via genome editing and characterized to determine the functional effects of this variant. We also examined the frequency of ER S118P in a case-control study (N = 536) of women with and without breast cancer with a familial risk.

RESULTS:

In heterozygous knock-in models, the S118P variant demonstrated no significant change in proliferation, migration, MAP Kinase pathway signaling, or response to the endocrine therapies tamoxifen and fulvestrant. Further, there was no difference in the prevalence of S118P between women with and without cancer relative to population registry databases.

CONCLUSIONS:

This study suggests that the ER S118P variant does not affect risk for breast cancer or hormone therapy resistance. Germline screening and modification of treatments for patients harboring this variant are likely not warranted.
Asunto(s)
Palabras clave
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Neoplasias de la Mama / Mutación de Línea Germinal / Antineoplásicos Hormonales / Receptor alfa de Estrógeno Tipo de estudio: Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Adult / Aged / Female / Humans / Middle aged Idioma: En Revista: Breast Cancer Res Treat Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Neoplasias de la Mama / Mutación de Línea Germinal / Antineoplásicos Hormonales / Receptor alfa de Estrógeno Tipo de estudio: Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Adult / Aged / Female / Humans / Middle aged Idioma: En Revista: Breast Cancer Res Treat Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos