Comprehensive genomic profiling can predict response to neoadjuvant chemotherapy in triple-negative breast cancer
Background: 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) t...
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Elsevier
2025-04-01
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| Series: | Breast |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0960977625000426 |
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| author | Monika Drobniene Dominyka Breimelyte Ieva Sadzeviciene Rasa Sabaliauskaite Ruta Barbora Valkiuniene Raimundas Meskauskas Daiva Dabkeviciene Sonata Jarmalaite |
| author_facet | Monika Drobniene Dominyka Breimelyte Ieva Sadzeviciene Rasa Sabaliauskaite Ruta Barbora Valkiuniene Raimundas Meskauskas Daiva Dabkeviciene Sonata Jarmalaite |
| author_sort | Monika Drobniene |
| collection | DOAJ |
| description | Background: 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. Methods: 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. Results: 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. Conclusions: 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. |
| format | Article |
| id | doaj-art-0da8a3b7215e4dd18073d51871e2ce78 |
| institution | DOAJ |
| issn | 1532-3080 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Elsevier |
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| series | Breast |
| spelling | doaj-art-0da8a3b7215e4dd18073d51871e2ce782025-08-20T02:50:48ZengElsevierBreast1532-30802025-04-018010442310.1016/j.breast.2025.104423Comprehensive genomic profiling can predict response to neoadjuvant chemotherapy in triple-negative breast cancerMonika Drobniene0Dominyka Breimelyte1Ieva Sadzeviciene2Rasa Sabaliauskaite3Ruta Barbora Valkiuniene4Raimundas Meskauskas5Daiva Dabkeviciene6Sonata Jarmalaite7National 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; Corresponding author. National Cancer Institute, Baublio st. 3b, LT-08406, 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, LithuaniaInstitute of Biosciences, Life Sciences Center, Vilnius University, Sauletekio Ave. 7, LT-10257, Vilnius, LithuaniaNational Cancer Institute, P. Baublio st. 3b, LT-08406, Vilnius, Lithuania; Institute of Biosciences, Life Sciences Center, Vilnius University, Sauletekio Ave. 7, LT-10257, Vilnius, LithuaniaNational Center of Pathology, Affiliate of Vilnius University Hospital Santaros Clinics, P. Baublio St. 5, LT-08406, Vilnius, LithuaniaNational Center of Pathology, Affiliate of Vilnius University Hospital Santaros Clinics, P. Baublio St. 5, LT-08406, Vilnius, LithuaniaNational Cancer Institute, P. Baublio st. 3b, LT-08406, Vilnius, Lithuania; Institute of Biosciences, Life Sciences Center, Vilnius University, Sauletekio Ave. 7, LT-10257, Vilnius, LithuaniaNational Cancer Institute, P. Baublio st. 3b, LT-08406, Vilnius, Lithuania; Institute of Biosciences, Life Sciences Center, Vilnius University, Sauletekio Ave. 7, LT-10257, Vilnius, LithuaniaBackground: 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. Methods: 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. Results: 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. Conclusions: 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.http://www.sciencedirect.com/science/article/pii/S0960977625000426Triple-negative breast cancerNeoadjuvant chemotherapyComprehensive genomic profiling |
| spellingShingle | Monika Drobniene Dominyka Breimelyte Ieva Sadzeviciene Rasa Sabaliauskaite Ruta Barbora Valkiuniene Raimundas Meskauskas Daiva Dabkeviciene Sonata Jarmalaite Comprehensive genomic profiling can predict response to neoadjuvant chemotherapy in triple-negative breast cancer Breast Triple-negative breast cancer Neoadjuvant chemotherapy Comprehensive genomic profiling |
| title | Comprehensive genomic profiling can predict response to neoadjuvant chemotherapy in triple-negative breast cancer |
| title_full | Comprehensive genomic profiling can predict response to neoadjuvant chemotherapy in triple-negative breast cancer |
| title_fullStr | Comprehensive genomic profiling can predict response to neoadjuvant chemotherapy in triple-negative breast cancer |
| title_full_unstemmed | Comprehensive genomic profiling can predict response to neoadjuvant chemotherapy in triple-negative breast cancer |
| title_short | Comprehensive genomic profiling can predict response to neoadjuvant chemotherapy in triple-negative breast cancer |
| title_sort | comprehensive genomic profiling can predict response to neoadjuvant chemotherapy in triple negative breast cancer |
| topic | Triple-negative breast cancer Neoadjuvant chemotherapy Comprehensive genomic profiling |
| url | http://www.sciencedirect.com/science/article/pii/S0960977625000426 |
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