Drobniene Monika, Breimelyte Dominyka, Sadzeviciene Ieva, Sabaliauskaite Rasa, Valkiuniene Ruta Barbora, Meskauskas Raimundas, Dabkeviciene Daiva, Jarmalaite Sonata
National Cancer Institute, P. Baublio st. 3b, LT-08406, Vilnius, Lithuania; Institute of Biosciences, Life Sciences Center, Vilnius University, Sauletekio Ave. 7, LT-10257, Vilnius, Lithuania.
National Cancer Institute, P. Baublio st. 3b, LT-08406, Vilnius, Lithuania; Institute of Biosciences, Life Sciences Center, Vilnius University, Sauletekio Ave. 7, LT-10257, Vilnius, Lithuania.
Breast. 2025 Apr;80:104423. doi: 10.1016/j.breast.2025.104423. Epub 2025 Feb 17.
The rate of pathological complete response (pCR) after neoadjuvant chemotherapy (NACT) in triple-negative breast cancer (TNBC) varies, and adjuvant therapy treatment for residual cancer remains a challenge. The aim of our study was to assess the added value of FoundationOne®CDx (F1CDx) testing in the non-metastatic TNBC in predicting responses to NACT and disease outcomes.
Ninety-three eligible patients with stage II-III TNBC were treated with NACT without immunotherapy. Response to NACT was evaluated postoperatively. Comprehensive genomic profiling with NGS-based molecular test F1CDx was performed on diagnostic biopsies (N = 93). Hierarchical clustering and logistic regression were applied for data analysis.
Genomic profiling and data clustering revealed heterogeneous genetic landscapes of TNBC with subsets displaying multilayered co-amplifications of oncogenes and overlapping changes in crucial signaling pathways. TP53 mutations were detected in 95 % of all TNBCs. BRCA1/BRCA2 mutations were significant molecular factors in predicting favorable responses to NACT (OR = 0.09, p = 0.002), while CCNDs co-mutations with FGFs (OR = 13.4, p = 0.016) and PI3Ks family mutations in AR-positive cases (OR = 6.1, p = 0.008) - poor responses. Low tumor mutational burden (TMB) ≤ 3 (OR = 9.4, p = 0.009) was a significant factor for the disease progression after NACT.
This study suggests that comprehensive CDx testing can be explored as a prognostic tool in early-stage TNBC to predict responses to NACT and disease progression. Based on these results, genomic analysis should be performed early in the patient journey, possibly guiding adjuvant treatment choices and participation in randomized clinical trials, mainly when pCR is not achieved, as the ultimate goal is improving patient outcomes.
三阴性乳腺癌（TNBC）新辅助化疗（NACT）后的病理完全缓解（pCR）率各不相同，对残留癌的辅助治疗仍然是一项挑战。我们研究的目的是评估FoundationOne®CDx（F1CDx）检测在非转移性TNBC中预测NACT反应和疾病转归的附加价值。
93例符合条件的II-III期TNBC患者接受了无免疫治疗的NACT。术后评估NACT反应。对诊断性活检标本（N = 93）进行基于二代测序（NGS）的分子检测F1CDx的综合基因组分析。采用层次聚类和逻辑回归进行数据分析。
基因组分析和数据聚类显示TNBC具有异质性基因图谱，亚组显示癌基因的多层共扩增以及关键信号通路的重叠变化。在所有TNBC中，95%检测到TP53突变。BRCA1/BRCA2突变是预测对NACT有良好反应的重要分子因素（比值比[OR]=0.09，p = 0.002），而CCNDs与FGFs的共突变（OR = 13.4，p = 0.016）以及AR阳性病例中的PI3Ks家族突变（OR = 6.1，p = 0.008）——提示反应不佳。低肿瘤突变负荷（TMB）≤3（OR = 9.4，p = 0.009）是NACT后疾病进展的重要因素。
本研究表明，综合CDx检测可作为早期TNBC的一种预后工具，用于预测对NACT的反应和疾病进展。基于这些结果，基因组分析应在患者病程早期进行，可能指导辅助治疗选择和参与随机临床试验，主要是在未达到pCR的情况下，因为最终目标是改善患者预后。
