Neoadjuvant Chemotherapy of Patients with Early Breast Cancer Is Associated with Increased Detection of Disseminated Tumor Cells in the Bone Marrow
Preclinical data suggest that neoadjuvant chemotherapy (NAT) may promote micrometastatic spread. We aimed to compare the detection rate and prognostic relevance of disseminated tumor cells (DTCs) from the bone marrow (BM) of patients with early-stage breast cancer (EBC) after NAT with that of therap...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-01-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/14/3/635 |
| _version_ | 1797488785148084224 |
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| author | Léa Volmer André Koch Sabine Matovina Dominik Dannehl Martin Weiss Ganna Welker Markus Hahn Tobias Engler Markus Wallwiener Christina Barbara Walter Ernst Oberlechner Sara Yvonne Brucker Klaus Pantel Andreas Hartkopf |
| author_facet | Léa Volmer André Koch Sabine Matovina Dominik Dannehl Martin Weiss Ganna Welker Markus Hahn Tobias Engler Markus Wallwiener Christina Barbara Walter Ernst Oberlechner Sara Yvonne Brucker Klaus Pantel Andreas Hartkopf |
| author_sort | Léa Volmer |
| collection | DOAJ |
| description | Preclinical data suggest that neoadjuvant chemotherapy (NAT) may promote micrometastatic spread. We aimed to compare the detection rate and prognostic relevance of disseminated tumor cells (DTCs) from the bone marrow (BM) of patients with early-stage breast cancer (EBC) after NAT with that of therapy-naive EBC patients. DTCs were identified from BM samples, collected during primary surgery. Patients who received NAT were compared to patients who received chemotherapy after surgery. In total, 809 patients were analyzed. After NAT, 45.4% of patients were DTC-positive as compared to 19.9% of patients in the adjuvant chemotherapy group (<i>p</i> < 0.001). When sampled in patients who had undergone NAT, the detection of DTCs in the BM was significantly increased (OR: 3.1; 95% confidence interval (CI): 2.1–4.4; <i>p</i> < 0.001). After NAT, DTC-positive patients with ≥2 DTCs per 1.5 × 10<sup>6</sup> mononuclear cells in their BM had an impaired disease-free survival (HR: 4.8, 95% CI: 0.9–26.6; <i>p</i> = 0.050) and overall survival (HR: 4.2; 95% CI: 1.4–12.7; <i>p</i> = 0.005). The higher rate of DTC-positive patients after NAT as compared to a treatment-naive comparable control cohort suggests that NAT supports tumor cell dissemination into the bone marrow. DTC positivity in BM predicted relapse in various distant organs, implying that tumor cell dissemination was not restricted to the bone marrow. |
| first_indexed | 2024-03-10T00:07:16Z |
| format | Article |
| id | doaj.art-7b060bb144d84b03b057968afa7e35d5 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T00:07:16Z |
| publishDate | 2022-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-7b060bb144d84b03b057968afa7e35d52023-11-23T16:06:07ZengMDPI AGCancers2072-66942022-01-0114363510.3390/cancers14030635Neoadjuvant Chemotherapy of Patients with Early Breast Cancer Is Associated with Increased Detection of Disseminated Tumor Cells in the Bone MarrowLéa Volmer0André Koch1Sabine Matovina2Dominik Dannehl3Martin Weiss4Ganna Welker5Markus Hahn6Tobias Engler7Markus Wallwiener8Christina Barbara Walter9Ernst Oberlechner10Sara Yvonne Brucker11Klaus Pantel12Andreas Hartkopf13Department of Women’s Health, University Medical Center Tübingen, 72076 Tübingen, GermanyResearch Institute for Women’s Health, University Medical Center Tübingen, 72076 Tübingen, GermanyDepartment of Women’s Health, University Medical Center Tübingen, 72076 Tübingen, GermanyDepartment of Women’s Health, University Medical Center Tübingen, 72076 Tübingen, GermanyDepartment of Women’s Health, University Medical Center Tübingen, 72076 Tübingen, GermanyResearch Institute for Women’s Health, University Medical Center Tübingen, 72076 Tübingen, GermanyDepartment of Women’s Health, University Medical Center Tübingen, 72076 Tübingen, GermanyDepartment of Women’s Health, University Medical Center Tübingen, 72076 Tübingen, GermanyDepartment of Gynecology and Obstetrics, University Medical Center Heidelberg, 69120 Heidelberg, GermanyDepartment of Women’s Health, University Medical Center Tübingen, 72076 Tübingen, GermanyDepartment of Women’s Health, University Medical Center Tübingen, 72076 Tübingen, GermanyDepartment of Women’s Health, University Medical Center Tübingen, 72076 Tübingen, GermanyDepartment of Tumor Biology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, GermanyDepartment of Women’s Health, University Medical Center Tübingen, 72076 Tübingen, GermanyPreclinical data suggest that neoadjuvant chemotherapy (NAT) may promote micrometastatic spread. We aimed to compare the detection rate and prognostic relevance of disseminated tumor cells (DTCs) from the bone marrow (BM) of patients with early-stage breast cancer (EBC) after NAT with that of therapy-naive EBC patients. DTCs were identified from BM samples, collected during primary surgery. Patients who received NAT were compared to patients who received chemotherapy after surgery. In total, 809 patients were analyzed. After NAT, 45.4% of patients were DTC-positive as compared to 19.9% of patients in the adjuvant chemotherapy group (<i>p</i> < 0.001). When sampled in patients who had undergone NAT, the detection of DTCs in the BM was significantly increased (OR: 3.1; 95% confidence interval (CI): 2.1–4.4; <i>p</i> < 0.001). After NAT, DTC-positive patients with ≥2 DTCs per 1.5 × 10<sup>6</sup> mononuclear cells in their BM had an impaired disease-free survival (HR: 4.8, 95% CI: 0.9–26.6; <i>p</i> = 0.050) and overall survival (HR: 4.2; 95% CI: 1.4–12.7; <i>p</i> = 0.005). The higher rate of DTC-positive patients after NAT as compared to a treatment-naive comparable control cohort suggests that NAT supports tumor cell dissemination into the bone marrow. DTC positivity in BM predicted relapse in various distant organs, implying that tumor cell dissemination was not restricted to the bone marrow.https://www.mdpi.com/2072-6694/14/3/635breast cancerdisseminated tumor cellsneoadjuvant chemotherapycirculating tumor cells |
| spellingShingle | Léa Volmer André Koch Sabine Matovina Dominik Dannehl Martin Weiss Ganna Welker Markus Hahn Tobias Engler Markus Wallwiener Christina Barbara Walter Ernst Oberlechner Sara Yvonne Brucker Klaus Pantel Andreas Hartkopf Neoadjuvant Chemotherapy of Patients with Early Breast Cancer Is Associated with Increased Detection of Disseminated Tumor Cells in the Bone Marrow Cancers breast cancer disseminated tumor cells neoadjuvant chemotherapy circulating tumor cells |
| title | Neoadjuvant Chemotherapy of Patients with Early Breast Cancer Is Associated with Increased Detection of Disseminated Tumor Cells in the Bone Marrow |
| title_full | Neoadjuvant Chemotherapy of Patients with Early Breast Cancer Is Associated with Increased Detection of Disseminated Tumor Cells in the Bone Marrow |
| title_fullStr | Neoadjuvant Chemotherapy of Patients with Early Breast Cancer Is Associated with Increased Detection of Disseminated Tumor Cells in the Bone Marrow |
| title_full_unstemmed | Neoadjuvant Chemotherapy of Patients with Early Breast Cancer Is Associated with Increased Detection of Disseminated Tumor Cells in the Bone Marrow |
| title_short | Neoadjuvant Chemotherapy of Patients with Early Breast Cancer Is Associated with Increased Detection of Disseminated Tumor Cells in the Bone Marrow |
| title_sort | neoadjuvant chemotherapy of patients with early breast cancer is associated with increased detection of disseminated tumor cells in the bone marrow |
| topic | breast cancer disseminated tumor cells neoadjuvant chemotherapy circulating tumor cells |
| url | https://www.mdpi.com/2072-6694/14/3/635 |
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