New developments in the epidemiology of breast cancer prognosis : molecular predictors of treatment response and survival

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New developments in the epidemiology of breast cancer prognosis : molecular predictors of treatment response and survival

 

Author: Foo, Man-ning Eleanor
Title: New developments in the epidemiology of breast cancer prognosis : molecular predictors of treatment response and survival
Degree: M.Sc.
Year: 2012
Subject: Breast -- Cancer -- Epidemiology.
Breast -- Cancer -- Treatment.
Breast -- Cancer -- Molecular aspects.
Hong Kong Polytechnic University -- Dissertations
Department: Dept. of Health Technology and Informatics
Pages: xiii, 151 leaves : ill. (chiefly col.), 1 col. map ; 30 cm.
Language: English
InnoPac Record: http://library.polyu.edu.hk/record=b2471065
URI: http://theses.lib.polyu.edu.hk/handle/200/6363
Abstract: Breast cancer treatment has experienced fundamental changes with the discovery of prognostic and predictive biomarkers that enable the application of personalized therapies to different molecular subtypes. With the introduction of improved imaging methods and screening programs, early diagnosis of breast cancer has become possible over the past decades. The paradigm shift highlights the need of biomarkers to identify the residual risk of breast cancer patients and to indicate the potential value of adjuvant therapy. To date, there are no useful tools to identify the patients who are benefit from the course of treatment. The inability of histologic grading system to estimate the prognosis of carcinoma and to evaluate its response to specific therapy prompts the researchers to determine the molecular features within tumour. Recent profiling studies of breast cancer have emphasized the relevance of tumour biology in the determination of breast cancer behaviour. Tumours of different histologic grades show distinct molecular profiles at the genomic and immunohistochemical levels. Several studies have shown that breast tumours can be stratified into subtypes similar to those defined by gene expression profiling using a panel of immunohistochemical markers. The aim of this study is to assess the molecular subtypes of breast cancer among patients in a dedicated breast care centre and to determine the treatment response and survival outcomes associated with distinct molecular subtypes. In carrying out this aim, the prevalence, clinicopathologic features of breast tumours according to molecular subtypes are also extensively studied.
Method: Non-invasive and invasive breast cancers of 107 patients were identified for analysis and tumours were classified into four subtypes based on immunohistochemical (IHC) assays of estrogen receptor (ER), progesterone receptor (PR) and HER-2: luminal A, luminal B, HER-2 and basal-like. Results: IHC subtypes were not associated with tumour size, lymphovascular invasion and lymph node involvement but differed by histologic grade (P = 0.014) and nuclear grade of tumours (P = 0.001) whereas marginally significant differences was observed for mitotic counts (P = 0.071). On the other hand, there were significant difference in patients receiving hormonal therapy (P < 0.01) and targeted therapy (P < 0.01). The 5-year overall survival estimates for patients with luminal A, luminal B, HER-2 and basal-like tumours were 100%, 96.2%, 71.4% and 92.3% respectively. Compared to the predominant luminal A tumours (93.4%), luminal B (80.8%), HER-2 (71.4%) and basal-like (76.9%) tumours exhibited a reduced disease-free survival (DFS). In terms of molecular biomarkers, patients with ER positive tumours had a higher DFS than patients with ER negative tumours (log-rank test = 4.4, P = 0.036). We also observed that patients with tumours having a low Ki-67 proliferation index were more likely to have favourable prognosis (log-rank test =5.4, P = 0.02). Conclusion: Our results provided evidence for classifying breast cancer into molecular subtypes which was distinct with respect to clinicopathologic variables, treatment response and survival outcomes. The new molecular classification demonstrated improvements on selection of adjuvant therapy for individual patients.

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