Multi-Gene Panel Testing for Hereditary Cancer Predisposition Among Patients Sixty-Five Years and Above Diagnosed With Breast Cancer.

IF 2.1 Q3 ONCOLOGY World Journal of Oncology Pub Date : 2024-10-01 Epub Date: 2024-09-16 DOI:10.14740/wjon1919

Hikmat Abdel-Razeq, Faris Tamimi, Baha Sharaf, Sarah M Nielsen, Brandie Heald, Kathryn E Hatchell, Edward D Esplin, Hira Bani Hani, Khansa Al-Azzam, Mais Alkyam, Rawan Mustafa, Areej Al-Atary

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Abstract

Background: The availability and affordability of germline genetic testing (GGT) has resulted in a broader utilization in daily clinical practice. However, adherence to testing guidelines is low, especially among older patients, where testing is often not offered.

Methods: In this study, consecutive, newly diagnosed patients with breast cancer (BC) aged ≥ 65 years and eligible for GGT, as per the National Comprehensive Cancer Network (NCCN) guidelines (version 1, 2021), were invited to participate, from March 2021 to December 2022. Patients were offered a restricted (two- or 20-gene panel), or an expanded 84-gene panel.

Results: During the study period, 204 patients were enrolled. The mean (standard deviation (SD)) age at BC diagnosis was 70.5 (5.13) years, ranging 65 - 81 years. All patients were Arab and the majority were Jordanian. The majority (n = 188, 92.2%) had early-stage (stages I and II) disease. One hundred three (50.5%) patients were tested with a restricted two-gene (n = 13) or 20-gene (n = 90) panel, while the remaining 101 (49.5%) patients had an expanded 84-gene panel. Family history of close blood relative(s) with BC was the most common indication for testing (n = 110, 53.9%). Among the entire study cohort, 22 (10.8%) had pathogenic/likely pathogenic germline variants (PGVs) and another 97 (47.5%) had ≥ 1 variants of uncertain significance (VUS). PGV rates were significantly higher with the expanded panel (14.9%) compared to restricted testing (6.8%) (P = 0.032). Similarly, VUS rates were significantly higher with the expanded panel (64.4%) compared to the restricted panel (31.1%) (P < 0.001). The most prevalent genes with PGVs were BRCA1/2 (31.3% of all PGV-positive patients), CHEK2 (23.1%) and ATM (19.2%).

Conclusion: GGT should not be overlooked in older BC patients, as this study demonstrates that > 10% of patients have PGVs, largely in potentially actionable genes.

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对六十五岁及以上确诊为乳腺癌的患者进行遗传性癌症易感性多基因组检测。

背景：种系基因检测（GGT）的可用性和可负担性使其在日常临床实践中得到了更广泛的应用。然而，对检测指南的依从性却很低，尤其是年龄较大的患者，他们通常不接受检测：本研究邀请年龄≥ 65 岁、符合美国国立综合癌症网络（NCCN）指南（2021 年第 1 版）规定的 GGT 检测条件的连续新诊断乳腺癌（BC）患者参加，时间为 2021 年 3 月至 2022 年 12 月。患者可接受限制性（2个或20个基因检测）或扩展的84个基因检测：在研究期间，共有 204 名患者入组。BC 诊断时的平均年龄（标准差（SD））为 70.5 (5.13)岁，从 65 岁到 81 岁不等。所有患者均为阿拉伯人，其中大多数为约旦人。大多数患者（n = 188，92.2%）病情处于早期（I 期和 II 期）。103 名患者（50.5%）接受了限制性双基因（13 人）或 20 个基因（90 人）检测，其余 101 名患者（49.5%）接受了扩展的 84 个基因检测。家族近亲中有 BC 患者是最常见的检测指征（110 人，占 53.9%）。在整个研究队列中，22 人（10.8%）有致病/可能致病的种系变异（PGV），另有 97 人（47.5%）有≥ 1 个意义不确定的变异（VUS）。与限制性检测（6.8%）相比，扩大样本组的 PGV 率（14.9%）明显更高（P = 0.032）。同样，与限制性检测（31.1%）相比，扩大检测范围（64.4%）的 VUS 率也明显更高（P < 0.001）。PGV最常见的基因是BRCA1/2（占所有PGV阳性患者的31.3%）、CHEK2（23.1%）和ATM（19.2%）：结论：在老年 BC 患者中，GGT 不应被忽视，因为这项研究表明，10% 以上的患者存在 PGV，其中大部分是潜在的可操作基因。

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来源期刊

World Journal of Oncology ONCOLOGY-

CiteScore

6.10

自引率

15.40%

发文量

期刊介绍： World Journal of Oncology, bimonthly, publishes original contributions describing basic research and clinical investigation of cancer, on the cellular, molecular, prevention, diagnosis, therapy and prognosis aspects. The submissions can be basic research or clinical investigation oriented. This journal welcomes those submissions focused on the clinical trials of new treatment modalities for cancer, and those submissions focused on molecular or cellular research of the oncology pathogenesis. Case reports submitted for consideration of publication should explore either a novel genomic event/description or a new safety signal from an oncolytic agent. The areas of interested manuscripts are these disciplines: tumor immunology and immunotherapy; cancer molecular pharmacology and chemotherapy; drug sensitivity and resistance; cancer epidemiology; clinical trials; cancer pathology; radiobiology and radiation oncology; solid tumor oncology; hematological malignancies; surgical oncology; pediatric oncology; molecular oncology and cancer genes; gene therapy; cancer endocrinology; cancer metastasis; prevention and diagnosis of cancer; other cancer related subjects. The types of manuscripts accepted are original article, review, editorial, short communication, case report, letter to the editor, book review.