Abstract P6-09-09: Meta-analysis of ESR1 mutation prevalence in metastatic breast cancer
Authors: Mandó P , Rizzo MM , Perez de la Puente C , Costanzo MV , Nervo A , Nadal J , Colo F , Loza CM , Loza J , Fabiano V , Ponce C , Chacon R 
Published: February 2018

Abstract
Introduction: ESR1 mutations were described for the first time in 1996 when different tyrosine 537 mutations were found to confer constitutive activation of the receptor, describing this region as a key factor in the ligand regulation of ER transcriptional activity. However, due to the low prevalence of this mutation in primary breast tumors its clinical significance maintained unknown. With the advent of large scale genomic analysis, a new understanding of breast cancer molecular characteristics has gained relevance. The low prevalence of ESR1 mutations in primary breast cancer has been confirmed but mutations in metastatic ER-positive breast cancers has been proved to be a completely different scenario. Nevertheless, information regarding real prevalence of ESR1 mutation in metastatic breast cancer is not known as selection of patients and molecular technique used are heterogeneous.
Sources: Search was carried by corresponding clinical oncologists of the Breast Cancer Unit of Alexander Fleming Institute. In March 2017, key words “ESR1 mutations”, “Estrogen receptor mutations” and “Breast cancer” were used as search strategy for the present meta-analysis in PubMed. Furthermore, abstracts from congress presentations were analyzed and hand searching from reference list of obtained articles was executed. Online search retrieved 60 articles published, 3 abstracts related were found and 3 further studies were detected by hand search. Articles were excluded if they only included primary tumors and not metastatic cases and if they were undertaken before 2000 due to important technical differences of mutation detection, including finally 23 cohorts.
Study Selection: Studies considered were prospective or retrospective cohorts of metastatic breast cancer patients with mutation analysis of tissue or circulating DNA. A data form was used by the primary reviewer to extract equivalent information from each article. Information extracted included population sampled, prevalence estimates, clinical characteristics of cohort, sample analyzed and technical procedure for mutation detection. A second reviewer blinded to the primary reviewer's decisions checked the article selection and data extraction. Any differences of opinion were discussed, and a third reviewer was available to arbitrate any issues.
Meta-analysis was undertaken using a random-effects model conducted using the metaprop function in Meta package of R studio Version 1.0.136 (© 2009-2016 RStudio, Inc.). PRISMA guidelines were followed in conducting and reporting the results.
Results and Discussion: Results show a prevalence of ESR1 mutation of 24% (CI95% 19-30%) in the 3607 patients included. Nevertheless, important heterogeneity (I2 =90%) is observed due to great differences in the articles published of this topic. This heterogeneity is attributed to the type of cohorts presented, the selection of patients, the technique used and type of sample studied, but another source of heterogeneity must be present as it still persists after grouping studies according to this variables. The importance of this analysis resides in the fact that it is the most complete information of the prevalence of this mutation that may have future importance in therapeutic decisions in metastatic breast cancer.
Citation Format: Mandó P, Rizzo MM, Perez de la Puente C, Costanzo MV, Nervo A, Nadal J, Colo F, Loza CM, Loza J, Fabiano V, Ponce C, Chacon R. Meta-analysis of ESR1 mutation prevalence in metastatic breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-09-09.