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Title: Changes in hormone receptors and proliferation markers in breast cancers treated with neoadjuvant letrozole and the relationship with response
Author: Murray, Juliette
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2007
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137 postmenopausal patients with locally advanced breast cancer were treated with 2.5mg letrozole daily. Tumour samples were taken at diagnosis at three months and, in 62 patients, additionally at 10-14 days. Patients with ER rich tumours were shown to be those most likely to derive maximal benefit from neoadjuvant letrozole. In this group 67% of patients showed a clinical response to treatment (>50% reduction in tumour volume at three months on USS) and 33% had their surgery downstaged from mastectomy to breast conserving surgery. Of the 125 patients who completed the 3 month audit period, with a mean follow up period of 39 months (4-58), 42 patients had died. Of these, 16 had evidence of recurrent breast cancer at the time of death. 7 local recurrences have occurred in the series (5%). 75% of tumours displayed evidence of a pathological response (decreased cellularity/increased fibrosis) at three months. Significant decreases in PgR expression were seen after both 14 days and three months but this did not correlate with clinical or pathological tumour response. Baseline proliferation was similar in responders and non-responders whether assessed clinically or pathologically. Treatment was associated with highly significant decreases in Ki67 and in all tumour subgroups at 14 days. There was no significant difference in Ki67 expression at 14 days between subsequent clinical responders and non-responders. However, when correlating the decrease in proliferation with pathological response, Ki67 expression at 14 days was significantly higher in tumours which subsequently failed to show morphological evidence of response. It remains to be seen whether these changes in morphology are associated with differences in tumour behaviour and long-term outcome. The fresh tissue collected in parallel with the formalin fixed tissue in this study is currently being analysed by microarray and will hopefully suggest possible avenues for other markers which may prove more helpful in predicting response to neoadjuvant endocrine treatment on an individual patient basis.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available