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dc.contributor.authorMurray, Julietteen
dc.date.accessioned2018-03-29T12:19:09Z
dc.date.available2018-03-29T12:19:09Z
dc.date.issued2007en
dc.identifier.urihttp://hdl.handle.net/1842/29288
dc.description.abstracten
dc.description.abstractThe aim of this study was to further characterise the clinical response to primary systemic endocrine therapy in breast cancer and to determine whether it is possible to identify biological markers of tumour phenotype that can be used to predict subsequent clinical response to neoadjuvant treatment with letrozole for three months.en
dc.description.abstract137 postmenopausal patients with locally advanced oestrogen receptor (ER) positive 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. Serial clinical tumour measurements were made over the three month treatment period. Ultrasound scanning (USS) was shown to be the most accurate method of assessing clinical response to treatment and the modality that corresponded most closely with pathological response. Patients with ER rich tumours were shown to be those most likely to derive maximal benefit from neoadjuvant letrozole.en
dc.description.abstractIn this series, 67% of patients showed a clinical response to treatment (> 50% reduction in tumour volume at three months on USS) and 63 % had their surgery down-staged 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%).en
dc.description.abstract75% 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, assessed using Ki67) was similar in responders and non-responders whether assessed clinically or pathologically. Treatment was associated with highly significant decreases in Ki67 in all tumour subgroups (at least P<0.005 by paired Wilcoxon rank test) 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.en
dc.description.abstractThe percentage reduction in Ki67 over the three month treatment period showed a significant correlation with cause specific survival (p=0.007). However, it was not possible to use changes in proliferation to predict response for an individual patient. 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 basisen
dc.publisherThe University of Edinburghen
dc.relation.isreferencedbyAlready catalogueden
dc.subjectAnnexe Thesis Digitisation Project 2018 Block 17en
dc.titleChanges in hormone receptors and proliferation markers in breast cancers treated with neoadjuvant letrozole and the relationship with responseen
dc.typeThesis or Dissertationen
dc.type.qualificationlevelDoctoralen
dc.type.qualificationnameMD Doctor of Medicineen


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