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Title: A study of biological characteristics of early operable primary breast cancer in older women and correlation with clinical outcome
Author: Syed, Binafsha Manzoor
ISNI:       0000 0004 2745 8038
Awarding Body: University of Nottingham
Current Institution: University of Nottingham
Date of Award: 2012
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Background Advancing age carries the highest risk of developing breast cancer and one-third of breast cancer cases develop in women over 70 years of age. With the elderly population increasing, the incidence of breast cancer in older women is also expected to rise in the near future. The management of breast cancer in older women appears complex, given their limited life expectancy, limited physiological reserves and related social issues. However, most of the available literature is based on studies which focus on younger patients, or the data are derived from registry databases. A number of trials are designed in such a way that older patients are either excluded or under- represented. Aims This thesis aims to analyse the biology of early operable primary breast cancer in older (::::70 years) women and correlate it with their clinical outcome, based on a large series from a single centre with long-term follow-up. Patients, Materials and Methods 1. A primary database including 1,758 consecutive older (::::70 years) women with early operable primary breast cancer who were managed in a dedicated service from 1973-2010 was established including information on basic clinicopathological features and long-term clinical outcome. 2. For those who underwent primary surgery, tissue microarrays (TMAs) were constructed for detailed biological analysis (N=575). The expression of ER, PgR, HER2, EGFR, HER3, HER4, Bc12, Muc1, BRCA1, BRCA2, p53, MDM2, MDM4, LKB1, E-Cadherin, CD44, VEGF, CK5, CK5/6, CK7/8, CK14, CK17, CK18 and CK19 were analysed using indirect immunohistochemistry on TMA blocks and Ki67 using whole tumour sections. Molecular classification was explored using clustering analysis. These biological characteristics were compared with those from a previously characterised series of younger «70 years) patients from the same unit. Results The clinical outcome appeared excellent in terms of breast cancer specific survival, where a considerable proportion died from causes other than breast cancer. The outcome has also shown significant further improvement in the last decade. The ER appeared as an independent prognostic factor and patients with strongly ER positive tumours, regardless of primary treatment, showed excellent clinical outcome - those with a tumour ER H-score >250 had similar breast cancer specific survival rates regardless of whether treatment was by primary endocrine therapy or surgery Primary breast cancer in older women appeared to have different biological characteristic including the existence of a novel cluster, low ER luminal, which was unique to the older population, with association with distinct clinical outcome. Overall they had a less aggress phenotype - dominated by tumours which had expression of ER and luminal cytokeratins, and. proliferation index. The ER appeared as the key factor for clinical outcome as well as the driver of the biomarkers, and age appeared as a surrogate. LKB I appeared to have a significant influence on the clinical outcome of adjuvant endocrine therapy. Conclusions The biology of breast cancer in older women appears to be different from that of their young counterparts and is associated with a different clinical outcome. The majority of older women to have less aggressive phenotypes (mainly ER positive tumours) and an excellent clinical outcome regardless of primary therapies based on a multi-disciplinary assessment in a dedicated clinical service. There is a minority (mainly ER negative) of tumours which are associated with an inferior outcome and they remain a therapeutic challenge.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available