Berg Tobias, Ahlborn Lise, Jensen Maj-Britt, Knoop Ann Søegaard, Ejlertsen Bent, Rossing Maria
Danish Breast Cancer Group, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark; Department of Oncology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark; Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
Neoplasia. 2025 May;63:101162. doi: 10.1016/j.neo.2025.101162. Epub 2025 Mar 22.
Among women with primary metastatic breast cancer (pMBC), around 5 % of women with primary invasive breast cancer, high-risk mutations associated with disease progression and poor prognosis is shown. The heterogeneity and clinical implications of these genomic alterations remains to be fully elucidated. We performed comprehensive gene mapping on 211 tumors of women diagnosed with pMBC at Rigshospitalet 2014-2021. After DNA purification 203 tumor samples were eligible for analysis. Median age in our cohort was 69 years, 68 % were ER-positive/HER2-negative, 23 % HER2-positive and 9 % triple-negative. A high tumor mutational burden (TMB), shown in 10 %, was in univariable analysis associated with a poor prognosis and a median overall survival of 5.3 months (95 % CI, 2.5-51.3) but no significant association after adjusting for subtype and age. 65 % of tumors had an actionable biomarker, including a PIK3CA mutation in 39 %. TP53 mutations were found in 33 % of tumors and were associated with an increased risk of death (adjusted HR: 1.60, 95 % CI; 1.07-2.40). We have found that for women with pMBC, the disease is driven by several targetable genetic mutations across subtypes, however our results suggest a reduced prognostic value of TMB for this complex patient group. Taken together, our findings substantiate the value of early genomic profiling to actively identify women that may be eligible for a more individualized treatment scheme.
在原发性转移性乳腺癌（pMBC）女性患者中，约5%的原发性浸润性乳腺癌女性患者显示出与疾病进展和预后不良相关的高危突变。这些基因组改变的异质性和临床意义仍有待充分阐明。我们对2014年至2021年在里格霍斯皮塔尔诊断为pMBC的211名女性的肿瘤进行了全面的基因图谱分析。DNA纯化后，203个肿瘤样本符合分析条件。我们队列中的中位年龄为69岁，68%为雌激素受体阳性/人表皮生长因子受体2阴性，23%为人表皮生长因子受体2阳性，9%为三阴性。10%的患者显示出高肿瘤突变负荷（TMB），单变量分析显示其与预后不良相关，中位总生存期为5.3个月（95%CI，2.5 - 51.3），但在调整亚型和年龄后无显著关联。65%的肿瘤具有可操作的生物标志物，其中39%存在PIK3CA突变。33%的肿瘤中发现了TP53突变，且与死亡风险增加相关（调整后风险比：1.60，95%CI；1.07 - 2.40）。我们发现，对于pMBC女性患者，该疾病由多种亚型的可靶向基因突变驱动，然而我们的结果表明TMB对这一复杂患者群体的预后价值降低。综上所述，我们的研究结果证实了早期基因组分析对于积极识别可能适合更个体化治疗方案的女性患者的价值。
