Estrogen-Receptor Loss and ESR1 Mutation in Estrogen-Receptor-Positive Metastatic Breast Cancer and the Effect on Overall Survival

• Published in: Cancers Vol. 16; no. 17; p. 3025
• Main Authors: Westenend, Pieter J, Meurs, Claudia J C, de Leeuw, Bertie, Akkers, Robert C
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 30-08-2024
• Subjects: Biopsy; Breast cancer; Cancer therapies; Chemotherapy; Electronic medical records; Endocrine therapy; ErbB-2 protein; Estrogen receptors; Estrogens; Genes; Kinases; Liver; Medical diagnosis; Metastases; Metastasis; Mutation; Mutation hot spots; Patients; Population studies; Statistical analysis; Survival; Tumors; United States > US; Netherlands; estrogen-receptor; breast cancer; ESR1 mutation; estrogen-receptor loss; metastasis; survival
• ISSN: 2072-6694; 2072-6694
• DOI: 10.3390/cancers16173025

In patients with metastatic estrogen-receptor (ER)-positive HER2-negative breast cancer, the loss of ER expression and the mutation of
-the gene encoding the ER receptor-are mechanisms for resistance to endocrine therapy. We aimed to determine the frequency of these mechanisms and their interaction. Metastases were retrieved from our pathology files.
hotspot mutations resulting in p.(D538G), p.(Y537S), and p.(L536H) were determined by means of pyrosequencing. Clinical data were retrieved from electronic medical records. A total of 136 metastases were available for analysis. ER loss was found in 23 metastases (17%).
mutations were found in 18 metastases (13%), including p.(D538G) in 9, p.(Y537S) in 7, and p.(L536H) in 2.
mutation and ER loss were mutually exclusive (
= 0.042), and
mutation was associated with endocrine therapy (
= 0.002).
mutation was found in two primary breast cancers.
mutations are rare in primary breast cancer and develop in metastases during endocrine therapy. Furthermore, ER loss had a statistically significant negative effect on overall survival when compared to patients without ER loss, with a rate ratio of 3.21 (confidence interval 1.95-5.26). No such effect was observed for
mutations, with a rate ratio of 1.15 (confidence interval 0.67-1.95). We conclude that ER loss and
mutation together account for 30% of the resistance to endocrine therapy.