Abstract PS13-46: Immunomodulation with dexamethasone in neoadjuvant chemotherapy for triple negative breast cancer
Authors: Daniel Goldstein, Mahmoud Kassem, Dionisia Quiroga, Abdul Miah, Craig Vargo, Namrata Vilas Shinde, Michael Berger, Nicole Williams, Daniel Stover, Sagar Sardesai, Maryam Lustberg, Bhuvaneswari Ramaswamy, Gary Tozbikian, Patrick Schnell, Mathew Cherian
Journal: Cancer Research (2021)

Abstract Introduction: The immunomodulatory effects of dexamethasone and prednisone have been a staple of chemotherapy regimens since Mustargen, Oncovin, procarbazine, prednisone (MOPP) was used to treat lymphomas in 1963. Since then steroids have become ubiquitous in chemotherapy and were transitioned to an anti-nausea medication in solid tumor therapies and now anti-inflammatory therapies for common side effects of immune checkpoint inhibitors. While some modern immunomodulator therapies like rituximab and mycophenolate mofetil work through specific mechanisms, steroids have a much more non-specific effect working through a wide variety of pathways. Traditionally, chemotherapies such as paclitaxel, doxorubicin, and cyclophosphamide have been thought to induce cell death purely through cell-autonomous mechanisms such as DNA damage or interference with accurate chromosome segregation during mitosis. More recently, the strong correlation between tumor-infiltrating lymphocytes (TILs) and pathological complete response (pCR) to chemotherapy has been demonstrated. We hypothesized that dexamethasone use may adversely affect the efficacy of chemotherapy due to down-regulation of TILs. Therefore, we investigated the effects of dexamethasone exposure levels on response rates to neoadjuvant therapy of triple negative breast cancer (TNBC) with doxorubicin, cyclophosphamide and paclitaxel. We evaluated TNBC due to its high sensitivity to chemotherapeutic agents in the neoadjuvant setting and because pCR following neoadjuvant chemotherapy is an indicator of better long-term outcomes in TNBC patients. Dexamethasone use as an anti-emetic in the neo-adjuvant setting is highly variable, often being substituted for with olanzapine. Methods: All patients with TNBC who received neo-adjuvant chemotherapy with doxorubicin and cyclophosphamide (AC) between January 1st, 2012 and November 31st, 2018 at The James Comprehensive Cancer Center at The Ohio State University were included in this retrospective study, which totaled 174 patients. We omitted patients who received carboplatin with the paclitaxel, or received other experimental therapies during the neoadjuvant period. The primary exposure was dexamethasone dose by chemotherapy cycle, and the primary outcome was pCR. We used logistic regression to perform an intent-to-treat analysis, and defined P&amp;lt;0.05 as the significant level. We adjusted for diabetes status, age, and metformin prescription. Results: We have found that there is no statistical or apparent difference in pCR by average dexamethasone dose per neoadjuvant chemotherapy cycle (P = 0.51), including when adjusting for diabetes status, metformin prescription and age (P=0.85). We found that there was sufficient variation in dexamethasone dose per cycle with the main mass of observations between 10 and 60 mg/cycle. Conclusions: We did not detect a difference in dexamethasone dose per neoadjuvant chemotherapy cycle between patients who did or did not achieve pCR. Thus, based on this retrospective analysis, the use of dexamethasone as an anti-emetic for triple negative breast cancer may not be harmful or beneficial in terms of the pathologic response to chemotherapy. This suggests that its use as an agent to mitigate side effects from chemotherapy is reasonable. Citation Format: Daniel Goldstein, Mahmoud Kassem, Dionisia Quiroga, Abdul Miah, Craig Vargo, Namrata Vilas Shinde, Michael Berger, Nicole Williams, Daniel Stover, Sagar Sardesai, Maryam Lustberg, Bhuvaneswari Ramaswamy, Gary Tozbikian, Patrick Schnell, Mathew Cherian. Immunomodulation with dexamethasone in neoadjuvant chemotherapy for triple negative breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS13-46.