دورية أكاديمية
The somatic mutation profile of estrogen receptor-positive HER2-negative metastatic breast cancer in Brazilian patients.
| العنوان: | The somatic mutation profile of estrogen receptor-positive HER2-negative metastatic breast cancer in Brazilian patients. |
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| المؤلفون: | Reinert T; Oncoclínicas & Co, São Paulo, Brazil.; Grupo Brasileiro de Estudos em Câncer de Mama (GBECAM), Porto Alegre, Brazil., do Rego FO; Oncoclínicas Precision Medicine (OCPM), São Paulo, Brazil., Silva MCE; Oncoclínicas Precision Medicine (OCPM), São Paulo, Brazil., Rodrigues AM; Oncoclínicas Precision Medicine (OCPM), São Paulo, Brazil., Koyama FC; Oncoclínicas Precision Medicine (OCPM), São Paulo, Brazil., Gonçalves AC; Oncoclínicas & Co, São Paulo, Brazil., Pauletto MM; Oncoclínicas & Co, São Paulo, Brazil., de Carvalho Oliveira LJ; Oncoclínicas & Co, São Paulo, Brazil., de Resende CAA; Oncoclínicas & Co, São Paulo, Brazil., Landeiro LCG; Oncoclínicas & Co, São Paulo, Brazil., Barrios CH; Oncoclínicas & Co, São Paulo, Brazil., Mano MS; Oncoclínicas & Co, São Paulo, Brazil., Dienstmann R; Oncoclínicas & Co, São Paulo, Brazil.; University of Vic - Central University of Catalonia, Vic, Spain. |
| المصدر: | Frontiers in oncology [Front Oncol] 2024 Jun 17; Vol. 14, pp. 1372947. Date of Electronic Publication: 2024 Jun 17 (Print Publication: 2024). |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Frontiers Research Foundation] Country of Publication: Switzerland NLM ID: 101568867 Publication Model: eCollection Cited Medium: Print ISSN: 2234-943X (Print) Linking ISSN: 2234943X NLM ISO Abbreviation: Front Oncol Subsets: PubMed not MEDLINE |
| أسماء مطبوعة: | Original Publication: [Lausanne : Frontiers Research Foundation] |
| مستخلص: | Background: Breast cancer is the leading cause of cancer death among women worldwide. Studies about the genomic landscape of metastatic breast cancer (MBC) have predominantly originated from developed nations. There are still limited data on the molecular epidemiology of MBC in low- and middle-income countries. This study aims to evaluate the prevalence of mutations in the PI3K-AKT pathway and other actionable drivers in estrogen receptor (ER)+/HER2- MBC among Brazilian patients treated at a large institution representative of the nation's demographic diversity. Methods: We conducted a retrospective observational study using laboratory data (OC Precision Medicine). Our study included tumor samples from patients with ER+/HER2- MBC who underwent routine tumor testing from 2020 to 2023 and originated from several Brazilian centers within the Oncoclinicas network. Two distinct next-generation sequencing (NGS) assays were used: GS Focus (23 genes, covering PIK3CA , AKT1 , ESR1 , ERBB2 , BRCA1 , BRCA2 , PALB2 , TP53 , but not PTEN ) or GS 180 (180 genes, including PTEN, tumor mutation burden [TMB] and microsatellite instability [MSI]). Results: Evaluation of tumor samples from 328 patients was undertaken, mostly (75.6%) with GS Focus. Of these, 69% were primary tumors, while 31% were metastatic lesions. The prevalence of mutations in the PI3K-AKT pathway was 39.3% (95% confidence interval, 33% to 43%), distributed as 37.5% in PIK3CA and 1.8% in AKT1 . Stratification by age revealed a higher incidence of mutations in this pathway among patients over 50 (44.5% vs 29.1%, p=0.01). Among the PIK3CA mutations, 78% were canonical (included in the alpelisib companion diagnostic non-NGS test), while the remaining 22% were characterized as non-canonical mutations (identifiable only by NGS test). ESR1 mutations were detected in 6.1%, exhibiting a higher frequency in metastatic samples (15.1% vs 1.3%, p=0.003). Additionally, mutations in BRCA1, BRCA2 , or PALB2 were identified in 3.9% of cases, while mutations in ERBB2 were found in 2.1%. No PTEN mutations were detected, nor were TMB high or MSI cases. Conclusion: We describe the genomic landscape of Brazilian patients with ER+/HER2- MBC, in which the somatic mutation profile is comparable to what is described in the literature globally. These data are important for developing precision medicine strategies in this scenario, as well as for health systems management and research initiatives. Competing Interests: Authors TR, AG, MP, LO, CR, LL, CB, MM, & RD were employed by the company Oncoclínicas & Co. TR – Research funding: AstraZeneca, Libbs. Speaker honoraria/advisory board: AstraZeneca, Daichi-Sankyo, Novartis, MSD, Lilly, Libbs. RD declares advisory role for Roche, Foundation Medicine, received a speaker’s fee from Roche, Ipsen, Amgen, Servier, Sanofi, Libbs, Merck Sharp & Dohme, Lilly, AstraZeneca, Janssen, Takeda, Bristol Myers Squibb, GlaxoSmithKline, Gilead, research grants from Merck, Novartis, Daiichi-Sankyo, GlaxoSmithKline and AstraZeneca, and is investor in Trialing Health, S.L. CB - Stock and Other Ownership Interests: Biomarker, MedSIR, Tummi. Speaker Honoraria: Novartis, Roche/Genentech, Pfizer, GlaxoSmithKline, Sanofi, Boehringer Ingelheim, Eisai. Consulting or Advisory Role: Boehringer Ingelheim, Roche/Genentech, Novartis, GlaxoSmithKline, Eisai,Pfizer, AstraZeneca, Libbs, MSD Oncology, United Medical. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2024 Reinert, do Rego, Silva, Rodrigues, Koyama, Gonçalves, Pauletto, de Carvalho Oliveira, de Resende, Landeiro, Barrios, Mano and Dienstmann.) |
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| فهرسة مساهمة: | Keywords: PI3K/Akt pathway; breast neoplasm; estrogen receptor; genomic landscape; targeted therapies |
| تواريخ الأحداث: | Date Created: 20240702 Latest Revision: 20240703 |
| رمز التحديث: | 20240703 |
| مُعرف محوري في PubMed: | PMC11215150 |
| DOI: | 10.3389/fonc.2024.1372947 |
| PMID: | 38952553 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 2234-943X |
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| DOI: | 10.3389/fonc.2024.1372947 |