Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA.
University of Texas Southwestern Medical School, Dallas, TX, USA.
Ann Surg Oncol. 2021 Jun;28(6):3383-3393. doi: 10.1245/s10434-020-09158-2. Epub 2020 Sep 29.
The moderate-penetrance germline mutations ATM, CHEK2, and PALB2 are implicated in an increased risk of the development of breast cancer. Whether these mutations provide clinical utility to guide treatment strategies and prognosis remains unknown.
A retrospective case-control study from a tertiary institution compared patients with stage 0-III breast cancer, and positive for ATM, CHEK2, or PALB2 mutations, with a matched cohort selected by randomization and negative for mutations. Data acquisition included demographics, histopathologic, treatment, and clinical outcome variables.
A total of 145 patients with breast cancer (144 female and 1 male) were analyzed-74 mutation-positive patients (24 ATM, 26 CHEK2, 24 PALB2) and 71 mutation-negative patients. Mutation-positive patients compared with mutation-negative patients had increased family history of breast cancer (79.7 vs. 52.9%, p < 0.001) and tumor size > 2.0 cm (63.1% vs. 42.3%, p = 0.015). Patients with prior knowledge of mutational status were more likely to proceed with total mastectomy and prophylactic mastectomy (74.5% vs. 25.5%, p < 0.02; and 65.5% vs. 34.5%, p < 0.001, respectively). The unadjusted recurrence rate was higher in mutation-positive patients compared with mutation-negative patients (24.3 vs. 8.5%, p = 0.01), although mutation status was not predictive for recurrence in Cox regression analysis.
Patients positive for ATM, CHEK2, or PALB2 mutations had increased tumor size and were more likely to undergo extensive surgeries. Mutation status was not predictive of recurrence, although this lack of effect may have been mitigated by lower rates of recurrence in those who pursued total mastectomy. Further studies are needed to confirm these findings.
中度外显率胚系突变 ATM、CHEK2 和 PALB2 与乳腺癌发病风险增加相关。这些突变是否能提供临床效用来指导治疗策略和预后尚不清楚。
这项来自一家三级医疗机构的回顾性病例对照研究比较了 0-III 期乳腺癌患者，这些患者的 ATM、CHEK2 或 PALB2 突变呈阳性，并与通过随机分组选择的、突变阴性的匹配队列进行比较。数据采集包括人口统计学、组织病理学、治疗和临床结局变量。
共分析了 145 例乳腺癌患者（144 名女性和 1 名男性），其中 74 例突变阳性患者（24 例 ATM、26 例 CHEK2、24 例 PALB2）和 71 例突变阴性患者。与突变阴性患者相比，突变阳性患者的乳腺癌家族史更多（79.7%比 52.9%，p<0.001），肿瘤直径>2.0cm 的比例更高（63.1%比 42.3%，p=0.015）。有突变状态既往知识的患者更有可能进行全乳房切除术和预防性乳房切除术（74.5%比 25.5%，p<0.02；65.5%比 34.5%，p<0.001）。未经调整的复发率在突变阳性患者中高于突变阴性患者（24.3%比 8.5%，p=0.01），尽管在 Cox 回归分析中突变状态不是复发的预测因素。
ATM、CHEK2 或 PALB2 突变阳性的患者肿瘤直径更大，更有可能进行广泛的手术。尽管在接受全乳房切除术的患者中，复发率较低可能减轻了这种影响，但突变状态与复发无关。需要进一步的研究来证实这些发现。
