The Immunomodulatory Effects of Dexamethasone on Neoadjuvant Chemotherapy for Triple-Negative Breast Cancer
Abstract Introduction The immunomodulatory impact of corticosteroids and concurrent chemotherapy is poorly understood within triple-negative breast cancer (TNBC). On a biochemical level, steroids have been linked to the signaling of chemotherapy-resistant pathways. However, on a clinical level, ster...
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| Format: | Article |
| Language: | English |
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Adis, Springer Healthcare
2023-06-01
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| Series: | Oncology and Therapy |
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| Online Access: | https://doi.org/10.1007/s40487-023-00235-6 |
| _version_ | 1827859791488221184 |
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| author | Kai Conrad Cecil Johnson Daniel Goldstein Jasmin Tharakan Dionisia Quiroga Mahmoud Kassem Michael Grimm Abdul Miah Craig Vargo Michael Berger Preeti Sudheendra Ashley Pariser Margaret E. Gatti-Mays Nicole Williams Daniel Stover Sagar Sardesai Robert Wesolowski Bhuvaneswari Ramaswamy Gary Tozbikian Patrick M. Schnell Mathew A. Cherian |
| author_facet | Kai Conrad Cecil Johnson Daniel Goldstein Jasmin Tharakan Dionisia Quiroga Mahmoud Kassem Michael Grimm Abdul Miah Craig Vargo Michael Berger Preeti Sudheendra Ashley Pariser Margaret E. Gatti-Mays Nicole Williams Daniel Stover Sagar Sardesai Robert Wesolowski Bhuvaneswari Ramaswamy Gary Tozbikian Patrick M. Schnell Mathew A. Cherian |
| author_sort | Kai Conrad Cecil Johnson |
| collection | DOAJ |
| description | Abstract Introduction The immunomodulatory impact of corticosteroids and concurrent chemotherapy is poorly understood within triple-negative breast cancer (TNBC). On a biochemical level, steroids have been linked to the signaling of chemotherapy-resistant pathways. However, on a clinical level, steroids play an essential role in chemotherapy tolerance through the prevention of chemotherapy-induced nausea and vomiting (CINV) and hypersensitivity reactions. Given these conflicting roles, we wanted to evaluate this interplay more rigorously in the context of early-stage TNBC. Methods We performed a retrospective analysis of patients with operable TNBC who received neoadjuvant chemotherapy (NAC) between January 2012 and November 2018, with the primary goal of examining the dose-dependent relationship between pathological complete response (pCR) rates and corticosteroid use. Secondary endpoints included the impact of steroid dosing on overall survival (OS) and recurrence-free survival (RFS), along with a breakdown in pCR rates based on steroid doses provided during each chemotherapy phase. Further adjusted analyses were performed based on patient age, diabetic status, and anatomical stage. Finally, we explored the relationship between tumor-infiltrating lymphocytes (TILs) seen on tissue samples at baseline and dexamethasone doses in terms of pCR rates. Results In total, of the 174 patients screened within this study period, 116 met full eligibility criteria. Of these eligible patients, all were female, with a median age of 51.5 years (27.0 to 74.0) and a mean body mass index (BMI) of 29.7 [standard deviation (SD) 7.04]. The majority were nondiabetic (80.2%). For cancer stage, 69.8% (n = 81) had stage 2 breast cancer. We found no statistically significant association between pCR rates and dexamethasone use, both in terms of the total dose (p = 0.55) and mean dose per NAC cycle (p = 0.74). Similarly, no difference was noted when adjusting for diabetic status, metformin use, or age at diagnosis, regardless of the total steroid dose provided (p = 0.72) or mean dose per cycle (p = 0.49). No meaningful changes to pCR rate were seen with higher mean or higher total steroid doses during the paclitaxel (T) phase (adjusted p = 0.16 and p = 0.76, respectively) or doxorubicin and cyclophosphamide (AC) phase (adjusted p = 0.83 and p = 0.77, respectively). Furthermore, we found no clinically significant association between dexamethasone dose and either RFS (p = 0.45) or OS (p = 0.89). Of the 56 patients who had available pre-treatment biopsy tissue samples, 27 achieved pCR, with higher TILs at baseline being associated with higher pCR rates, regardless of the mean dexamethasone dose used. Conclusion Our findings demonstrate that dexamethasone has no clinically significant impact on pCR, RFS, or OS when given concurrently with NAC in patients with curative TNBC, regardless of diabetic status. |
| first_indexed | 2024-03-12T13:13:36Z |
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| id | doaj.art-951fd11c96b2499b9c3ae9275fe18e77 |
| institution | Directory Open Access Journal |
| issn | 2366-1070 2366-1089 |
| language | English |
| last_indexed | 2024-03-12T13:13:36Z |
| publishDate | 2023-06-01 |
| publisher | Adis, Springer Healthcare |
| record_format | Article |
| series | Oncology and Therapy |
| spelling | doaj.art-951fd11c96b2499b9c3ae9275fe18e772023-08-27T11:12:36ZengAdis, Springer HealthcareOncology and Therapy2366-10702366-10892023-06-0111336137410.1007/s40487-023-00235-6The Immunomodulatory Effects of Dexamethasone on Neoadjuvant Chemotherapy for Triple-Negative Breast CancerKai Conrad Cecil Johnson0Daniel Goldstein1Jasmin Tharakan2Dionisia Quiroga3Mahmoud Kassem4Michael Grimm5Abdul Miah6Craig Vargo7Michael Berger8Preeti Sudheendra9Ashley Pariser10Margaret E. Gatti-Mays11Nicole Williams12Daniel Stover13Sagar Sardesai14Robert Wesolowski15Bhuvaneswari Ramaswamy16Gary Tozbikian17Patrick M. Schnell18Mathew A. Cherian19Division of Medical Oncology, Wexner Medical Center, The OH State University Comprehensive Cancer Center-James Cancer Hospital and Solove Research InstituteDivision of Internal Medicine, Bozeman HealthDivision of Medical Oncology, Wexner Medical Center, The OH State University Comprehensive Cancer Center-James Cancer Hospital and Solove Research InstituteDivision of Medical Oncology, Wexner Medical Center, The OH State University Comprehensive Cancer Center-James Cancer Hospital and Solove Research InstituteDepartment of Surgery, Mercy Health West HospitalDivision of Medical Oncology, Wexner Medical Center, The OH State University Comprehensive Cancer Center-James Cancer Hospital and Solove Research InstituteDivision of Medical Oncology, Wexner Medical Center, The OH State University Comprehensive Cancer Center-James Cancer Hospital and Solove Research InstituteDivision of Medical Oncology, Wexner Medical Center, The OH State University Comprehensive Cancer Center-James Cancer Hospital and Solove Research InstituteDivision of Medical Oncology, Wexner Medical Center, The OH State University Comprehensive Cancer Center-James Cancer Hospital and Solove Research InstituteDivision of Medical Oncology, Wexner Medical Center, The OH State University Comprehensive Cancer Center-James Cancer Hospital and Solove Research InstituteDivision of Medical Oncology, Wexner Medical Center, The OH State University Comprehensive Cancer Center-James Cancer Hospital and Solove Research InstituteDivision of Medical Oncology, Wexner Medical Center, The OH State University Comprehensive Cancer Center-James Cancer Hospital and Solove Research InstituteDivision of Medical Oncology, Wexner Medical Center, The OH State University Comprehensive Cancer Center-James Cancer Hospital and Solove Research InstituteDivision of Medical Oncology, Wexner Medical Center, The OH State University Comprehensive Cancer Center-James Cancer Hospital and Solove Research InstituteDivision of Medical Oncology, Wexner Medical Center, The OH State University Comprehensive Cancer Center-James Cancer Hospital and Solove Research InstituteDivision of Medical Oncology, Wexner Medical Center, The OH State University Comprehensive Cancer Center-James Cancer Hospital and Solove Research InstituteDivision of Medical Oncology, Wexner Medical Center, The OH State University Comprehensive Cancer Center-James Cancer Hospital and Solove Research InstituteDepartment of Pathology, Wexner Medical Center, The Ohio State UniversityDivision of Biostatistics, The Ohio State University College of Public HealthDivision of Medical Oncology, Wexner Medical Center, The OH State University Comprehensive Cancer Center-James Cancer Hospital and Solove Research InstituteAbstract Introduction The immunomodulatory impact of corticosteroids and concurrent chemotherapy is poorly understood within triple-negative breast cancer (TNBC). On a biochemical level, steroids have been linked to the signaling of chemotherapy-resistant pathways. However, on a clinical level, steroids play an essential role in chemotherapy tolerance through the prevention of chemotherapy-induced nausea and vomiting (CINV) and hypersensitivity reactions. Given these conflicting roles, we wanted to evaluate this interplay more rigorously in the context of early-stage TNBC. Methods We performed a retrospective analysis of patients with operable TNBC who received neoadjuvant chemotherapy (NAC) between January 2012 and November 2018, with the primary goal of examining the dose-dependent relationship between pathological complete response (pCR) rates and corticosteroid use. Secondary endpoints included the impact of steroid dosing on overall survival (OS) and recurrence-free survival (RFS), along with a breakdown in pCR rates based on steroid doses provided during each chemotherapy phase. Further adjusted analyses were performed based on patient age, diabetic status, and anatomical stage. Finally, we explored the relationship between tumor-infiltrating lymphocytes (TILs) seen on tissue samples at baseline and dexamethasone doses in terms of pCR rates. Results In total, of the 174 patients screened within this study period, 116 met full eligibility criteria. Of these eligible patients, all were female, with a median age of 51.5 years (27.0 to 74.0) and a mean body mass index (BMI) of 29.7 [standard deviation (SD) 7.04]. The majority were nondiabetic (80.2%). For cancer stage, 69.8% (n = 81) had stage 2 breast cancer. We found no statistically significant association between pCR rates and dexamethasone use, both in terms of the total dose (p = 0.55) and mean dose per NAC cycle (p = 0.74). Similarly, no difference was noted when adjusting for diabetic status, metformin use, or age at diagnosis, regardless of the total steroid dose provided (p = 0.72) or mean dose per cycle (p = 0.49). No meaningful changes to pCR rate were seen with higher mean or higher total steroid doses during the paclitaxel (T) phase (adjusted p = 0.16 and p = 0.76, respectively) or doxorubicin and cyclophosphamide (AC) phase (adjusted p = 0.83 and p = 0.77, respectively). Furthermore, we found no clinically significant association between dexamethasone dose and either RFS (p = 0.45) or OS (p = 0.89). Of the 56 patients who had available pre-treatment biopsy tissue samples, 27 achieved pCR, with higher TILs at baseline being associated with higher pCR rates, regardless of the mean dexamethasone dose used. Conclusion Our findings demonstrate that dexamethasone has no clinically significant impact on pCR, RFS, or OS when given concurrently with NAC in patients with curative TNBC, regardless of diabetic status.https://doi.org/10.1007/s40487-023-00235-6Triple-negative breast cancer (TNBC)Pathological complete response (pCR)SteroidsNeoadjuvant chemotherapyTaxaneAnthracycline |
| spellingShingle | Kai Conrad Cecil Johnson Daniel Goldstein Jasmin Tharakan Dionisia Quiroga Mahmoud Kassem Michael Grimm Abdul Miah Craig Vargo Michael Berger Preeti Sudheendra Ashley Pariser Margaret E. Gatti-Mays Nicole Williams Daniel Stover Sagar Sardesai Robert Wesolowski Bhuvaneswari Ramaswamy Gary Tozbikian Patrick M. Schnell Mathew A. Cherian The Immunomodulatory Effects of Dexamethasone on Neoadjuvant Chemotherapy for Triple-Negative Breast Cancer Oncology and Therapy Triple-negative breast cancer (TNBC) Pathological complete response (pCR) Steroids Neoadjuvant chemotherapy Taxane Anthracycline |
| title | The Immunomodulatory Effects of Dexamethasone on Neoadjuvant Chemotherapy for Triple-Negative Breast Cancer |
| title_full | The Immunomodulatory Effects of Dexamethasone on Neoadjuvant Chemotherapy for Triple-Negative Breast Cancer |
| title_fullStr | The Immunomodulatory Effects of Dexamethasone on Neoadjuvant Chemotherapy for Triple-Negative Breast Cancer |
| title_full_unstemmed | The Immunomodulatory Effects of Dexamethasone on Neoadjuvant Chemotherapy for Triple-Negative Breast Cancer |
| title_short | The Immunomodulatory Effects of Dexamethasone on Neoadjuvant Chemotherapy for Triple-Negative Breast Cancer |
| title_sort | immunomodulatory effects of dexamethasone on neoadjuvant chemotherapy for triple negative breast cancer |
| topic | Triple-negative breast cancer (TNBC) Pathological complete response (pCR) Steroids Neoadjuvant chemotherapy Taxane Anthracycline |
| url | https://doi.org/10.1007/s40487-023-00235-6 |
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