Electronic Thesis and Dissertation Repository

Degree

Doctor of Philosophy

Program

Pathology

Supervisor

Ann Chambers

Abstract

Locally advanced breast cancer (LABC) represents 15% of all non-metastatic breast cancers, with an overall poor prognosis, despite current guidelines that recommend neoadjuvant chemotherapy followed by surgery and adjuvant radiation. Therefore, a novel treatment paradigm using concurrent neoadjuvant chemoradiotherapy was proposed. A clinical trial was designed, where 32 LABC patients were treated with q3 weekly 5-fluorouracil, epirubicin and cyclophosphamide for three cycles, followed by weekly docetaxel for 9 weeks with concurrent regional radiation (45+5.4Gy) for the first 6 weeks. Patients subsequently underwent modified radical mastectomies. Pathological complete responses (pCR) and 3 year overall survival rates were compared to a matched concurrent control cohort. The concurrent chemoradiation cohort saw a significant increase in pCR rate and a trend toward 15% improvement in overall survival that failed to reach statistical significance. This regimen was not without toxicity, and 25% of patients experienced grade 3 or greater dermatitis and 25% experienced grade 3 or greater pneumonitis, resulting in one death. Tumour biomarker, plasma osteopontin, prior to chemotherapy was found to significantly predict for overall survival. In conclusion, LABC is an aggressive subset of breast cancer for which novel regimens must continue to be developed, taking advantage of the improved response to treatment with radiosensitivity seen in this concurrent chemoradiation regimen, but using alternative radiosensitizing agents to minimize toxicity.

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