Date of Award
Breast cancer, Carboplatin, Cyclophosphamide, Doxorubicin, Paclitaxel, Chemotherapy treatments
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This work is licensed under a Creative Commons Attribution 4.0 International License.
Breast cancer accounts for 25% of all cancers in Canadian women, and 15-20% of these are triple-negative breast cancers (TNBC), which have a poorer prognosis than other breast cancer subtypes. TNBC lacks expression of the estrogen receptor, progesterone receptor, and the human epidermal growth factor receptor 2 (HER2), which are common therapeutic targets in breast cancer. Due to the lack of target therapy, generalized chemotherapy treatments are used instead. The standard of care for treatment of TNBC instead consists of doxorubicin (A), cyclophosphamide (C) paclitaxel (T), and carboplatin (Carbo), that target various aspects of the cell cycle to induce cell cycle arrest. Pre-clinical models may be tested to determine how the administrative timing of ACT+Carbo may affect efficacy of treatments. The purpose of this study was to determine how the addition and timing of TNBC treatments influence cell cycle progression and how pre-clinical models can be used to optimize current ACT+Carbo treatments. MDA-MB-231 and MDA-MB-468 TNBC cells were treated with AC, T, TCarbo, or Carbo at various time points in vitro. Flow cytometry, trypan blue exclusion assay, and MTT were used to determine cell cycle progression, proliferation rate, and synergy. Casper zebrafish were used as an in vivo model. It was found that the combination pattern of T/TCarbo resulted in increased efficacy comparable to all other combinations via pre-clinical models. This information may be appliable to current TNBC treatments to improve efficacy, lower toxicity, and increase the 5-year survival rate of TNBC patients.
Mailloux, Emily, "The Influence of Administrative Timing in Triple-Negative Breast Cancer Treatments" (2023). Electronic Theses and Dissertations. 9068.