Association between homologous recombination deficiency and outcomes with platinum and platinum-free chemotherapy in patients with triple-negative breast cancer
Objective: The choice of chemotherapeutic regimen for triple-negative breast cancer (TNBC) remains controversial. Homologous recombination deficiency (HRD) has attracted increasing attention in informing chemotherapy treatment. This study was aimed at investigating the feasibility of HRD as a clinic...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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China Anti-Cancer Association
2023-02-01
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| Series: | Cancer Biology & Medicine |
| Subjects: | |
| Online Access: | https://www.cancerbiomed.org/content/20/2/155 |
| _version_ | 1828000519544635392 |
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| author | Yimeng Chen Xue Wang Feng Du Jian Yue Yiran Si Xiaochen Zhao Lina Cui Bei Zhang Ting Bei Binghe Xu Peng Yuan |
| author_facet | Yimeng Chen Xue Wang Feng Du Jian Yue Yiran Si Xiaochen Zhao Lina Cui Bei Zhang Ting Bei Binghe Xu Peng Yuan |
| author_sort | Yimeng Chen |
| collection | DOAJ |
| description | Objective: The choice of chemotherapeutic regimen for triple-negative breast cancer (TNBC) remains controversial. Homologous recombination deficiency (HRD) has attracted increasing attention in informing chemotherapy treatment. This study was aimed at investigating the feasibility of HRD as a clinically actionable biomarker for platinum-containing and platinum-free therapy. Methods: Chinese patients with TNBC who received chemotherapy between May 1, 2008 and March 31, 2020 were retrospectively analyzed with a customized 3D-HRD panel. HRD positivity was defined by an HRD score ≥ 30 or deleterious BRCA1/2 mutation. A total of 386 chemotherapy-treated patients with TNBC were screened from a surgical cohort (NCT01150513) and a metastatic cohort, and 189 patients with available clinical and tumor sequencing data were included. Results: In the entire cohort, 49.2% (93/189) of patients were identified as HRD positive (40 with deleterious BRCA1/2 mutations and 53 with BRCA1/2 intact with an HRD score of ≥ 30). In the first-line metastatic setting, platinum therapy was associated with longer median progression-free survival (mPFS) than platinum-free therapy [9.1 vs. 3.0 months; hazard ratio (HR), 0.43; 95% confidence interval 0.22–0.84; P = 0.01]. Among HRD-positive patients, the mPFS was significantly longer in those treated with platinum rather than platinum-free therapy (13.6 vs. 2.0 months; HR, 0.11; P = 0.001). Among patients administered a platinum-free regimen, HRD-negative patients showed a PFS significantly superior to that of HRD-positive patients (P = 0.02; treatment-biomarker P-interaction = 0.001). Similar results were observed in the BRCA1/2-intact subset. In the adjuvant setting, HRD-positive patients tended to benefit more from platinum chemotherapy than from platinum-free chemotherapy (P = 0.05, P-interaction = 0.02). Conclusions: HRD characterization may guide decision-making regarding the use of platinum treatment in patients with TNBC in both adjuvant and metastatic settings. |
| first_indexed | 2024-04-10T06:15:45Z |
| format | Article |
| id | doaj.art-fd973b336f42493883a24e0714c2307a |
| institution | Directory Open Access Journal |
| issn | 2095-3941 |
| language | English |
| last_indexed | 2024-04-10T06:15:45Z |
| publishDate | 2023-02-01 |
| publisher | China Anti-Cancer Association |
| record_format | Article |
| series | Cancer Biology & Medicine |
| spelling | doaj.art-fd973b336f42493883a24e0714c2307a2023-03-02T08:55:43ZengChina Anti-Cancer AssociationCancer Biology & Medicine2095-39412023-02-0120215516810.20892/j.issn.2095-3941.2022.0525Association between homologous recombination deficiency and outcomes with platinum and platinum-free chemotherapy in patients with triple-negative breast cancerYimeng Chen0Xue Wang1Feng Du2Jian Yue3Yiran Si4Xiaochen Zhao5Lina Cui6Bei Zhang7Ting Bei8Binghe Xu9Peng Yuan10Department of Medical Oncology and Clinical Trial Center, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, ChinaDepartment of VIP Medical Services, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, ChinaDepartment of Medical Oncology and Clinical Trial Center, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, ChinaDepartment of VIP Medical Services, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, ChinaDepartment of Medical Oncology and Clinical Trial Center, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, ChinaThe Medical Department, 3D Medicines Inc., Shanghai 201114, ChinaThe Medical Department, 3D Medicines Inc., Shanghai 201114, ChinaThe Medical Department, 3D Medicines Inc., Shanghai 201114, ChinaThe Medical Department, 3D Medicines Inc., Shanghai 201114, ChinaDepartment of Medical Oncology and Clinical Trial Center, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, ChinaDepartment of VIP Medical Services, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, ChinaObjective: The choice of chemotherapeutic regimen for triple-negative breast cancer (TNBC) remains controversial. Homologous recombination deficiency (HRD) has attracted increasing attention in informing chemotherapy treatment. This study was aimed at investigating the feasibility of HRD as a clinically actionable biomarker for platinum-containing and platinum-free therapy. Methods: Chinese patients with TNBC who received chemotherapy between May 1, 2008 and March 31, 2020 were retrospectively analyzed with a customized 3D-HRD panel. HRD positivity was defined by an HRD score ≥ 30 or deleterious BRCA1/2 mutation. A total of 386 chemotherapy-treated patients with TNBC were screened from a surgical cohort (NCT01150513) and a metastatic cohort, and 189 patients with available clinical and tumor sequencing data were included. Results: In the entire cohort, 49.2% (93/189) of patients were identified as HRD positive (40 with deleterious BRCA1/2 mutations and 53 with BRCA1/2 intact with an HRD score of ≥ 30). In the first-line metastatic setting, platinum therapy was associated with longer median progression-free survival (mPFS) than platinum-free therapy [9.1 vs. 3.0 months; hazard ratio (HR), 0.43; 95% confidence interval 0.22–0.84; P = 0.01]. Among HRD-positive patients, the mPFS was significantly longer in those treated with platinum rather than platinum-free therapy (13.6 vs. 2.0 months; HR, 0.11; P = 0.001). Among patients administered a platinum-free regimen, HRD-negative patients showed a PFS significantly superior to that of HRD-positive patients (P = 0.02; treatment-biomarker P-interaction = 0.001). Similar results were observed in the BRCA1/2-intact subset. In the adjuvant setting, HRD-positive patients tended to benefit more from platinum chemotherapy than from platinum-free chemotherapy (P = 0.05, P-interaction = 0.02). Conclusions: HRD characterization may guide decision-making regarding the use of platinum treatment in patients with TNBC in both adjuvant and metastatic settings.https://www.cancerbiomed.org/content/20/2/155homologous recombination deficiencytriple-negative breast cancerplatinumsurvivalbrca |
| spellingShingle | Yimeng Chen Xue Wang Feng Du Jian Yue Yiran Si Xiaochen Zhao Lina Cui Bei Zhang Ting Bei Binghe Xu Peng Yuan Association between homologous recombination deficiency and outcomes with platinum and platinum-free chemotherapy in patients with triple-negative breast cancer Cancer Biology & Medicine homologous recombination deficiency triple-negative breast cancer platinum survival brca |
| title | Association between homologous recombination deficiency and outcomes with platinum and platinum-free chemotherapy in patients with triple-negative breast cancer |
| title_full | Association between homologous recombination deficiency and outcomes with platinum and platinum-free chemotherapy in patients with triple-negative breast cancer |
| title_fullStr | Association between homologous recombination deficiency and outcomes with platinum and platinum-free chemotherapy in patients with triple-negative breast cancer |
| title_full_unstemmed | Association between homologous recombination deficiency and outcomes with platinum and platinum-free chemotherapy in patients with triple-negative breast cancer |
| title_short | Association between homologous recombination deficiency and outcomes with platinum and platinum-free chemotherapy in patients with triple-negative breast cancer |
| title_sort | association between homologous recombination deficiency and outcomes with platinum and platinum free chemotherapy in patients with triple negative breast cancer |
| topic | homologous recombination deficiency triple-negative breast cancer platinum survival brca |
| url | https://www.cancerbiomed.org/content/20/2/155 |
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