Schuch Jaqueline Bohrer, Bordignon Cláudia, Rosa Mahira Lopes, de Baumont Angélica Cerveira, Bessel Marina, Macedo Gabriel S, Rosa Daniela Dornelles
Responsabilidade Social, Hospital Moinhos de Vento, Porto Alegre, RS, Brazil.
Molecular Pathology, Rede D'Or São Luiz, São Paulo, Brazil.
Front Oncol. 2024 Mar 13;14:1350162. doi: 10.3389/fonc.2024.1350162. eCollection 2024.
Breast and prostate cancers are the most common malignancies diagnosed in women and men respectively, and present with great clinical heterogeneity, even in tumors with the same histology and same site of origin. Somatic and germline molecular alterations in DNA may have prognostic and predictive impact, influencing response to therapies and overall survival. Our aim is to characterize the somatic and germline genomic landscape of women with locally advanced HER2-positive breast cancer and men with metastatic prostate cancer in Brazil. Secondarily, we aim to identify genetic variants associated with tumor prognosis and treatment response, identify patients carrying pathogenic alterations in cancer-predisposing genes, and characterize the genetic ancestry of the population included in the study.
This observational multicenter cohort study will include 550 adult patients from the five macro-regions of Brazil, divided into two arms: 1) breast cancer and 2) prostate cancer. Clinical and pathological data will be collected, as well as DNA samples from peripheral blood and tumor samples. In arm 1, the inclusion criteria are a histological diagnosis of breast carcinoma with overexpression of HER-2, clinical stage II or III, and current neoadjuvant treatment with chemotherapy plus trastuzumab. In arm 2, the criterion is a histological diagnosis of prostate adenocarcinoma, clinical stage IV. Whole-exome sequencing (WES) will be performed to identify variants that may be drivers and/or actionable in a specific patient or tumor. These variants will be interpreted and classified according to their population frequencies, predictors, functional studies, and literature data, following international guidelines proposed by expert societies.
This trial will contribute to the construction of a robust database that should provide a better understanding of the genomic profile of patients with breast and prostate cancer in Brazil. Considering the miscegenation of the Brazilian population, knowledge generated from these data will have implications for future studies of this specific population.
[clinicaltrial.gov], identifier [NCT05306600].
乳腺癌和前列腺癌分别是女性和男性中最常见的恶性肿瘤，即使在组织学类型相同且起源部位相同的肿瘤中，也表现出极大的临床异质性。DNA中的体细胞和种系分子改变可能具有预后和预测作用，影响对治疗的反应和总生存期。我们的目的是描绘巴西局部晚期HER2阳性乳腺癌女性患者和转移性前列腺癌男性患者的体细胞和种系基因组图谱。其次，我们旨在识别与肿瘤预后和治疗反应相关的基因变异，识别携带癌症易感基因致病性改变的患者，并描绘纳入研究人群的遗传血统。
这项观察性多中心队列研究将纳入来自巴西五个大区域的550名成年患者，分为两组：1）乳腺癌组和2）前列腺癌组。将收集临床和病理数据，以及外周血DNA样本和肿瘤样本。在第1组中，纳入标准为组织学诊断为HER-2过表达的乳腺癌、临床分期为II期或III期，以及目前正在接受化疗加曲妥珠单抗的新辅助治疗。在第2组中，标准为组织学诊断为前列腺腺癌、临床分期为IV期。将进行全外显子测序（WES）以识别可能是特定患者或肿瘤中的驱动因素和/或可操作的变异。这些变异将根据其人群频率、预测指标、功能研究和文献数据，按照专家协会提出的国际指南进行解释和分类。
该试验将有助于构建一个强大的数据库，该数据库应能更好地了解巴西乳腺癌和前列腺癌患者的基因组特征。考虑到巴西人群的混血情况，从这些数据中产生的知识将对该特定人群未来的研究产生影响。
[clinicaltrial.gov]，标识符[NCT05306600]。
