Date of Award

2024

Degree Name

Doctor of Philosophy

Schools and Centres

Medicine

First Supervisor

Professor Nehmat Houssami

Second Supervisor

Professor Max Bulsara

Abstract

This dissertation aimed to investigate the population-level incidence, site, and survival of recurrent metastatic breast cancer (rMBC) occurring after stage I−III breast cancer, and changes over time. Breast cancer mortality has declined over the last 30 years due to advances in screening, diagnosis, and treatment. However, the impact of improved cancer care on rMBC is not yet well understood because cancer registries do not routinely report on cancer recurrence (Chapter 1). A systematic review of 20 population-based studies provided evidence of improvements in survival for people with de novo metastatic breast cancer (stage IV at diagnosis) since 1995 in high-income countries. However, data for people with rMBC, who represent most new diagnoses of metastatic breast cancer, were limited (Chapter 2). An Australian population-based record linkage study was designed to address the research questions for rMBC. The study population comprised two cohorts of females with a first diagnosis of primary non-metastatic invasive breast cancer registered in the New South Wales Cancer Registry in 2001−2002 and 2006−2007 (Chapter 3).

Key findings

were: For the 2001−2002 cohort (n=6388), the 14-year cumulative incidence of rMBC was 22.2% (95% confidence interval (CI) 21.1−23.2%) (Chapter 4). For the 2006−2007 cohort (n=6832), the 9-year cumulative incidence of rMBC was 3.6% (95% CI 2.3%−4.9%) lower for the 2006−2007 cohort (15.0%) than the 2001−2002 cohort (18.6%), with increased use of adjuvant therapy observed in the 2006−2007 cohort (Chapter 5). For those with rMBC (n=2267), the 2006−2007 cohort were more likely to have an initial diagnosis of regional disease than localised disease and were older at first rMBC record than the 2001−2002 cohort. Despite these poorer prognostic characteristics, post-metastasis survival was similar between the two study cohorts (5-year probability of breast cancer death: 2001−2002 65% (95%CI 60–66%); 2006−2007 63% (95%CI 62–68%), p=0.13) (Chapter 6).

These findings can inform planning for breast cancer services for treatment and supportive care, counselling patients, and future research. The methods developed can be applied to new cohorts to investigate the population impact of ongoing treatment changes, used to inform the development of cancer registry systems to routinely report on rMBC, and extended to other cancers (Chapter 7).

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