Racial disparity in tumor microenvironment and distant recurrence in residual breast cancer after neoadjuvant chemotherapy
Abstract Black, compared to white, women with residual estrogen receptor-positive (ER+) breast cancer after neoadjuvant chemotherapy (NAC) have worse distant recurrence-free survival (DRFS). Such racial disparity may be due to difference in density of portals for systemic cancer cell dissemination,...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-06-01
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| Series: | npj Breast Cancer |
| Online Access: | https://doi.org/10.1038/s41523-023-00547-w |
| _version_ | 1797429420888162304 |
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| author | Gina Kim Burcu Karadal-Ferrena Jiyue Qin Ved P. Sharma Isabelle S. Oktay Yu Lin Xianjun Ye Saeed Asiry Jessica M. Pastoriza Esther Cheng Nurfiza Ladak John S. Condeelis Esther Adler Paula S. Ginter Timothy D’Alfonso David Entenberg Xiaonan Xue Joseph A. Sparano Maja H. Oktay |
| author_facet | Gina Kim Burcu Karadal-Ferrena Jiyue Qin Ved P. Sharma Isabelle S. Oktay Yu Lin Xianjun Ye Saeed Asiry Jessica M. Pastoriza Esther Cheng Nurfiza Ladak John S. Condeelis Esther Adler Paula S. Ginter Timothy D’Alfonso David Entenberg Xiaonan Xue Joseph A. Sparano Maja H. Oktay |
| author_sort | Gina Kim |
| collection | DOAJ |
| description | Abstract Black, compared to white, women with residual estrogen receptor-positive (ER+) breast cancer after neoadjuvant chemotherapy (NAC) have worse distant recurrence-free survival (DRFS). Such racial disparity may be due to difference in density of portals for systemic cancer cell dissemination, called TMEM doorways, and pro-metastatic tumor microenvironment (TME). Here, we evaluate residual cancer specimens after NAC from 96 Black and 87 white women. TMEM doorways are visualized by triple immunohistochemistry, and cancer stem cells by immunofluorescence for SOX9. The correlation between TMEM doorway score and pro-metastatic TME parameters with DRFS is examined using log-rank and multivariate Cox regression. Black, compared to white, patients are more likely to develop distant recurrence (49% vs 34.5%, p = 0.07), receive mastectomy (69.8% vs 54%, p = 0.04), and have higher grade tumors (p = 0.002). Tumors from Black patients have higher TMEM doorway and macrophages density overall (p = 0.002; p = 0.002, respectively) and in the ER+/HER2- (p = 0.02; p = 0.02, respectively), but not in the triple negative disease. Furthermore, high TMEM doorway score is associated with worse DRFS. TMEM doorway score is an independent prognostic factor in the entire study population (HR, 2.02; 95%CI, 1.18–3.46; p = 0.01), with a strong trend in ER+/HER2- disease (HR, 2.38; 95%CI, 0.96–5.95; p = 0.06). SOX9 expression is not associated with racial disparity in TME or outcome. In conclusion, higher TMEM doorway density in residual breast cancer after NAC is associated with higher distant recurrence risk, and Black patients are associated with higher TMEM doorway density, suggesting that TMEM doorway density may contribute to racial disparities in breast cancer. |
| first_indexed | 2024-03-09T09:12:56Z |
| format | Article |
| id | doaj.art-709b4bab0c9a4e758abfcd34536d7c48 |
| institution | Directory Open Access Journal |
| issn | 2374-4677 |
| language | English |
| last_indexed | 2024-03-09T09:12:56Z |
| publishDate | 2023-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Breast Cancer |
| spelling | doaj.art-709b4bab0c9a4e758abfcd34536d7c482023-12-02T07:53:34ZengNature Portfolionpj Breast Cancer2374-46772023-06-019111110.1038/s41523-023-00547-wRacial disparity in tumor microenvironment and distant recurrence in residual breast cancer after neoadjuvant chemotherapyGina Kim0Burcu Karadal-Ferrena1Jiyue Qin2Ved P. Sharma3Isabelle S. Oktay4Yu Lin5Xianjun Ye6Saeed Asiry7Jessica M. Pastoriza8Esther Cheng9Nurfiza Ladak10John S. Condeelis11Esther Adler12Paula S. Ginter13Timothy D’Alfonso14David Entenberg15Xiaonan Xue16Joseph A. Sparano17Maja H. Oktay18Department of Surgery, Albert Einstein College of Medicine/Montefiore Medical CenterDepartment of Pathology, Albert Einstein College of Medicine/Montefiore Medical CenterDepartment of Epidemiology & Population Health, Albert Einstein College of Medicine/Montefiore Medical CenterBio-Imaging Resource Center, The Rockefeller UniversityCollege of Art and Sciences, New York UniversityDepartment of Pathology, Albert Einstein College of Medicine/Montefiore Medical CenterDepartment of Pathology, Albert Einstein College of Medicine/Montefiore Medical CenterDepartment of Pathology, Batterjee Medical CollegeDepartment of Surgery, Albert Einstein College of Medicine/Montefiore Medical CenterCPL PathologyDepartment of Pathology, NYU Grossman School of MedicineDepartment of Surgery, Albert Einstein College of Medicine/Montefiore Medical CenterDepartment of Pathology, NYU Grossman School of MedicineDepartment of Pathology, NYU Long Island School of MedicineDepartment of Pathology, Memorial Sloan Kettering Cancer CenterDepartment of Pathology, Albert Einstein College of Medicine/Montefiore Medical CenterDepartment of Epidemiology & Population Health, Albert Einstein College of Medicine/Montefiore Medical CenterDivision of Hematology/Oncology, Icahn School of Medicine at Mount Sinai, Tisch Cancer InstituteDepartment of Surgery, Albert Einstein College of Medicine/Montefiore Medical CenterAbstract Black, compared to white, women with residual estrogen receptor-positive (ER+) breast cancer after neoadjuvant chemotherapy (NAC) have worse distant recurrence-free survival (DRFS). Such racial disparity may be due to difference in density of portals for systemic cancer cell dissemination, called TMEM doorways, and pro-metastatic tumor microenvironment (TME). Here, we evaluate residual cancer specimens after NAC from 96 Black and 87 white women. TMEM doorways are visualized by triple immunohistochemistry, and cancer stem cells by immunofluorescence for SOX9. The correlation between TMEM doorway score and pro-metastatic TME parameters with DRFS is examined using log-rank and multivariate Cox regression. Black, compared to white, patients are more likely to develop distant recurrence (49% vs 34.5%, p = 0.07), receive mastectomy (69.8% vs 54%, p = 0.04), and have higher grade tumors (p = 0.002). Tumors from Black patients have higher TMEM doorway and macrophages density overall (p = 0.002; p = 0.002, respectively) and in the ER+/HER2- (p = 0.02; p = 0.02, respectively), but not in the triple negative disease. Furthermore, high TMEM doorway score is associated with worse DRFS. TMEM doorway score is an independent prognostic factor in the entire study population (HR, 2.02; 95%CI, 1.18–3.46; p = 0.01), with a strong trend in ER+/HER2- disease (HR, 2.38; 95%CI, 0.96–5.95; p = 0.06). SOX9 expression is not associated with racial disparity in TME or outcome. In conclusion, higher TMEM doorway density in residual breast cancer after NAC is associated with higher distant recurrence risk, and Black patients are associated with higher TMEM doorway density, suggesting that TMEM doorway density may contribute to racial disparities in breast cancer.https://doi.org/10.1038/s41523-023-00547-w |
| spellingShingle | Gina Kim Burcu Karadal-Ferrena Jiyue Qin Ved P. Sharma Isabelle S. Oktay Yu Lin Xianjun Ye Saeed Asiry Jessica M. Pastoriza Esther Cheng Nurfiza Ladak John S. Condeelis Esther Adler Paula S. Ginter Timothy D’Alfonso David Entenberg Xiaonan Xue Joseph A. Sparano Maja H. Oktay Racial disparity in tumor microenvironment and distant recurrence in residual breast cancer after neoadjuvant chemotherapy npj Breast Cancer |
| title | Racial disparity in tumor microenvironment and distant recurrence in residual breast cancer after neoadjuvant chemotherapy |
| title_full | Racial disparity in tumor microenvironment and distant recurrence in residual breast cancer after neoadjuvant chemotherapy |
| title_fullStr | Racial disparity in tumor microenvironment and distant recurrence in residual breast cancer after neoadjuvant chemotherapy |
| title_full_unstemmed | Racial disparity in tumor microenvironment and distant recurrence in residual breast cancer after neoadjuvant chemotherapy |
| title_short | Racial disparity in tumor microenvironment and distant recurrence in residual breast cancer after neoadjuvant chemotherapy |
| title_sort | racial disparity in tumor microenvironment and distant recurrence in residual breast cancer after neoadjuvant chemotherapy |
| url | https://doi.org/10.1038/s41523-023-00547-w |
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